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Sestan M, Arsov T, Kifer N, Frkovic M, Grguric D, Ellyard J, Cook M, Vinuesa CG, Jelusic M. Whole exome sequencing in patients with childhood-onset systemic lupus erythematosus: Results from a Croatian national study. Scand J Immunol 2024; 100:e13411. [PMID: 39380326 DOI: 10.1111/sji.13411] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2024] [Revised: 09/15/2024] [Accepted: 09/24/2024] [Indexed: 10/10/2024]
Abstract
The purpose of this study was to identify new and low-frequency gene variants using whole exome sequencing (WES) in patients with childhood-onset systemic lupus erythematosus (cSLE), that may be involved in the pathogenesis of SLE. We performed WES on selected 17 trios (in some cases including other informative family members) in which the proband presented with severe, atypical clinical features, resistance to conventional therapy, a family pattern of occurrence and/or syndromic characteristics. After performing WES and analysis of gene variants, 17 novel and/or low-frequency variants were identified in 7 patients. One variant was classified as pathogenic (KMT2D, NM_003482.3:c.8626delC, predicted to truncate the protein p.(Gln2876Serfs*34)) and two as likely pathogenic according to the American College of Medical Genetics and Genomics classification guidelines (ADAR, NM_001111.3:c.2815A>G, predicted to encode p.(Ile939Val); BLK, NM_001715.2:c.211G>A, predicted to encode p.(Ala71Thr)). The other variants remain of uncertain significance at this point of time. WES is an important diagnostic and research instrument, producing a growing list of likely genes and gene variants that may be of relevance in the pathogenesis of cSLE and potentially point to novel therapeutic targets.
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Affiliation(s)
- Mario Sestan
- Department of Paediatrics, University of Zagreb School of Medicine, University Hospital Centre Zagreb, Zagreb, Croatia
| | - Todor Arsov
- Faculty of Medical Sciences, University Goce Delchev, Shtip, North Macedonia
- The Francis Crick Institute, London, UK
| | - Nastasia Kifer
- Department of Paediatrics, University of Zagreb School of Medicine, University Hospital Centre Zagreb, Zagreb, Croatia
| | - Marijan Frkovic
- Department of Paediatrics, University of Zagreb School of Medicine, University Hospital Centre Zagreb, Zagreb, Croatia
| | - Danica Grguric
- Department of Paediatrics, University of Zagreb School of Medicine, University Hospital Centre Zagreb, Zagreb, Croatia
| | - Julia Ellyard
- Department of Immunology and Infectious Diseases, The John Curtin School of Medical Research, Australian National University, Canberra, Australian Capital Territory, Australia
| | - Matthew Cook
- Department of Immunology and Infectious Diseases, The John Curtin School of Medical Research, Australian National University, Canberra, Australian Capital Territory, Australia
- University of Cambridge, Cambridge, UK
| | - Carola G Vinuesa
- The Francis Crick Institute, London, UK
- Department of Immunology and Infectious Diseases, The John Curtin School of Medical Research, Australian National University, Canberra, Australian Capital Territory, Australia
| | - Marija Jelusic
- Department of Paediatrics, University of Zagreb School of Medicine, University Hospital Centre Zagreb, Zagreb, Croatia
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Elshafei AA, Ibrahim EI, Abdellatif KF, Salem AEAK, Moustafa KA, Al-Doss AA, Migdadi HM, Hussien AM, Soufan W, Abd El Rahman T, Eldemery SM. Molecular and agro-morphological characterization of new barley genotypes in arid environments. BMC Biotechnol 2024; 24:41. [PMID: 38862994 PMCID: PMC11167802 DOI: 10.1186/s12896-024-00861-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2024] [Accepted: 05/16/2024] [Indexed: 06/13/2024] Open
Abstract
BACKGROUND Genetic diversity, population structure, agro-morphological traits, and molecular characteristics, are crucial for either preserving genetic resources or developing new cultivars. Due to climate change, water availability for agricultural use is progressively diminishing. This study used 100 molecular markers (25 TRAP, 22 SRAP, 23 ISTR, and 30 SSR). Additionally, 15 morphological characteristics were utilized to evaluate the optimal agronomic traits of 12 different barley genotypes under arid conditions. RESULTS Substantial variations, ranging from significant to highly significant, were observed in the 15 agromorphological parameters evaluated among the 12 genotypes. The KSU-B101 barley genotype demonstrated superior performance in five specific traits: spike number per plant, 100-grain weight, spike number per square meter, harvest index, and grain yield. These results indicate its potential for achieving high yields in arid regions. The Sahrawy barley genotype exhibited the highest values across five parameters, namely leaf area, spike weight per plant, spike length, spike weight per square meter, and biological yield, making it a promising candidate for animal feed. The KSU-B105 genotype exhibited early maturity and a high grain count per spike, which reflects its early maturity and ability to produce a high number of grains per spike. This suggests its suitability for both animal feed and human food in arid areas. Based on marker data, the molecular study found that the similarity coefficients between the barley genotypes ranged from 0.48 to 0.80, with an average of 0.64. The dendrogram constructed from these data revealed three distinct clusters with a similarity coefficient of 0.80. Notably, the correlation between the dendrogram and its similarity matrix was high (0.903), indicating its accuracy in depicting the genetic relationships. The combined analysis revealed a moderate correlation between the morphological and molecular analysis, suggesting alignment between the two characterization methods. CONCLUSIONS The morphological and molecular analyses of the 12 barley genotypes in this study effectively revealed the varied genetic characteristics of their agro-performance in arid conditions. KSU-B101, Sahrawy, and KSU-B105 have emerged as promising candidates for different agricultural applications in arid regions. Further research on these genotypes could reveal their full potential for breeding programs.
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Affiliation(s)
- Adel A Elshafei
- Genetics and Cytology Department, Genetic Engineering and Biotechnology Research Institute, National Research Center, Dokki, Giza, 12622, Egypt.
| | - Eid I Ibrahim
- Plant Production Department, College of Food and Agriculture Sciences, King Saud University, P.O. Box 2460, Riyadh, 11451, Saudi Arabia
| | - Kamal F Abdellatif
- Plant Biotechnology Department, Genetic Engineering & Biotechnology Research Institute (GEBRI), University of Sadat City, Sadat, Egypt
| | - Abd El-Azeem K Salem
- Field Crops Research Department, Agricultural and Biological Research Institute, National Research Center, Dokki, Giza, 12622, Egypt
| | - Khaled A Moustafa
- Barley Research Department, Field Crops Research Institute, Agricultural Research Center, Giza, 12619, Egypt
| | - Abdullah A Al-Doss
- Plant Production Department, College of Food and Agriculture Sciences, King Saud University, P.O. Box 2460, Riyadh, 11451, Saudi Arabia
| | - Hussein M Migdadi
- Plant Production Department, College of Food and Agriculture Sciences, King Saud University, P.O. Box 2460, Riyadh, 11451, Saudi Arabia
| | - Amal M Hussien
- Genetic Resources Research Department, Field Crops Research Institute, Agricultural Research Center, Giza, 12619, Egypt
| | - Walid Soufan
- Plant Production Department, College of Food and Agriculture Sciences, King Saud University, P.O. Box 2460, Riyadh, 11451, Saudi Arabia
| | - Taha Abd El Rahman
- Département de Biologie, Faculté des Sciences, Université de Sherbrooke, Sherbrooke, QC, J1K 2R1, Canada
| | - Samah M Eldemery
- Molecular Biology Department, Genetic Engineering & Biotechnology Research Institute (GEBRI), University of Sadat City, Sadat, Egypt
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Li Q, Bian J, Qian Y, Kossinna P, Gau C, Gordon PMK, Zhou X, Guo X, Yan J, Wu J, Long Q. An expression-directed linear mixed model discovering low-effect genetic variants. Genetics 2024; 226:iyae018. [PMID: 38314848 PMCID: PMC11630775 DOI: 10.1093/genetics/iyae018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2023] [Revised: 11/29/2023] [Accepted: 01/05/2024] [Indexed: 02/07/2024] Open
Abstract
Detecting genetic variants with low-effect sizes using a moderate sample size is difficult, hindering downstream efforts to learn pathology and estimating heritability. In this work, by utilizing informative weights learned from training genetically predicted gene expression models, we formed an alternative approach to estimate the polygenic term in a linear mixed model. Our linear mixed model estimates the genetic background by incorporating their relevance to gene expression. Our protocol, expression-directed linear mixed model, enables the discovery of subtle signals of low-effect variants using moderate sample size. By applying expression-directed linear mixed model to cohorts of around 5,000 individuals with either binary (WTCCC) or quantitative (NFBC1966) traits, we demonstrated its power gain at the low-effect end of the genetic etiology spectrum. In aggregate, the additional low-effect variants detected by expression-directed linear mixed model substantially improved estimation of missing heritability. Expression-directed linear mixed model moves precision medicine forward by accurately detecting the contribution of low-effect genetic variants to human diseases.
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Affiliation(s)
- Qing Li
- Department of Biochemistry & Molecular Biology, University of Calgary, Calgary T2N 1N4, Canada
| | - Jiayi Bian
- Department of Mathematics and Statistics, University of Calgary, Calgary T2N 1N4, Canada
| | - Yanzhao Qian
- Department of Mathematics and Statistics, University of Calgary, Calgary T2N 1N4, Canada
| | - Pathum Kossinna
- Department of Biochemistry & Molecular Biology, University of Calgary, Calgary T2N 1N4, Canada
| | - Cooper Gau
- Department of Mathematics and Statistics, University of Calgary, Calgary T2N 1N4, Canada
| | - Paul M K Gordon
- Alberta Children's Hospital Research Institute, University of Calgary, Calgary T2N 1N4, Canada
| | - Xiang Zhou
- School of Public Health, University of Michigan, Ann Arbor 48109, USA
| | - Xingyi Guo
- Department of Medicine & Biomedical Informatics, Vanderbilt University Medical Center, Nashville 37203, USA
| | - Jun Yan
- Physiology and Pharmacology, University of Calgary, Calgary T2N 1N4, Canada
- Hotchkiss Brain Institute, University of Calgary, Calgary T2N 1N4, Canada
| | - Jingjing Wu
- Department of Mathematics and Statistics, University of Calgary, Calgary T2N 1N4, Canada
| | - Quan Long
- Department of Biochemistry & Molecular Biology, University of Calgary, Calgary T2N 1N4, Canada
- Department of Mathematics and Statistics, University of Calgary, Calgary T2N 1N4, Canada
- Alberta Children's Hospital Research Institute, University of Calgary, Calgary T2N 1N4, Canada
- Hotchkiss Brain Institute, University of Calgary, Calgary T2N 1N4, Canada
- Department of Medical Genetics, University of Calgary, Calgary T2N 1N4, Canada
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Habib Z, Ijaz S, Haq IU, Hashem A, Avila-Quezada GD, Abd_Allah EF, Khan NA. Empirical phenotyping and genome-wide association study reveal the association of panicle architecture with yield in Chenopodium quinoa. Front Microbiol 2024; 15:1349239. [PMID: 38562468 PMCID: PMC10982352 DOI: 10.3389/fmicb.2024.1349239] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2023] [Accepted: 02/27/2024] [Indexed: 04/04/2024] Open
Abstract
Chenopodium quinoa manifests adaptability to grow under varying agro-climatic scenarios. Assessing quinoa germplasm's phenotypic and genetic variability is a prerequisite for introducing it as a potential candidate in cropping systems. Adaptability is the basic outcome of ecological genomics of crop plants. Adaptive variation predicted with a genome-wide association study provides a valuable basis for marker-assisted breeding. Hence, a panel of 72 quinoa plants was phenotyped for agro morphological attributes and association-mapping for distinct imperative agronomic traits. Inter simple sequence repeat (ISSR) markers were employed to assess genetic relatedness and population structure. Heatmap analysis showed three genotypes were early maturing, and six genotypes were attributed for highest yield. The SD-121-07 exhibited highest yield per plant possessing green, glomerulate shaped, compact density panicle with less leaves. However, SJrecm-03 yielded less exhibiting pink, intermediate shape, intermediate density panicles with less leaves. The phenotyping revealed strong correlation of panicle architecture with yield in quinoa. A genome-wide association study unraveled the associations between ISSR makers and agro-morphological traits. Mixed linear modes analysis yielded nine markers associated with eight traits at p ≤ 0.01. Moreover, ISSR markers significantly associated with panicle shape and leafiness were also associated with yield per plant. These findings contribute to the provision of authenticity for marker-assisted selection that ultimately would support quinoa breeding programs.
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Affiliation(s)
- Zakia Habib
- Centre of Agricultural Biochemistry and Biotechnology (CABB), University of Agriculture, Faisalabad, Pakistan
| | - Siddra Ijaz
- Centre of Agricultural Biochemistry and Biotechnology (CABB), University of Agriculture, Faisalabad, Pakistan
| | - Imran Ul Haq
- Department of Plant Pathology, University of Agriculture, Faisalabad, Pakistan
| | - Abeer Hashem
- Botany and Microbiology Department, College of Science, King Saud University, Riyadh, Saudi Arabia
| | | | - Elsayed Fathi Abd_Allah
- Plant Production Department, College of Food and Agricultural Sciences, King Saud University, Riyadh, Saudi Arabia
| | - Nasir Ahmad Khan
- Department of Plant Pathology, University of Agriculture, Faisalabad, Pakistan
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Yadav J, Jasrotia P, Jaglan MS, Sareen S, Kashyap PL, Kumar S, Yadav SS, Singh G, Singh GP. Unravelling the novel genetic diversity and marker-trait associations of corn leaf aphid resistance in wheat using microsatellite markers. PLoS One 2024; 19:e0289527. [PMID: 38386640 PMCID: PMC10883527 DOI: 10.1371/journal.pone.0289527] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2023] [Accepted: 10/17/2023] [Indexed: 02/24/2024] Open
Abstract
The study was conducted to identify novel simple sequence repeat (SSR) markers associated with resistance to corn aphid (CLA), Rhopalosiphum maidis L. in 48 selected bread wheat (Triticum aestivum L.) and wild wheat (Aegilops spp. & T. dicoccoides) genotypes during two consecutive cropping seasons (2018-19 and 2019-20). A total of 51 polymorphic markers containing 143 alleles were used for the analysis. The frequency of the major allele ranged from 0.552 (Xgwm113) to 0.938 (Xcfd45, Xgwm194 and Xgwm526), with a mean of 0.731. Gene diversity ranged from 0.116 (Xgwm526) to 0.489 (Xgwm113), with a mean of 0.354. The polymorphic information content (PIC) value for the SSR markers ranged from 0.107 (Xgwm526) to 0.370 (Xgwm113) with a mean of 0.282. The results of the STRUCTURE analysis revealed the presence of four main subgroups in the populations. Analysis of molecular variance (AMOVA) showed that the between-group difference was around 37 per cent of the total variation contributed to the diversity by the whole germplasm, while 63 per cent of the variation was attributed between individuals within the group. A general linear model (GLM) was used to identify marker-trait associations, which detected a total of 23 and 27 significant new marker-trait associations (MTAs) at the p < 0.01 significance level during the 2018-19 and 2019-20 crop seasons, respectively. The findings of this study have important implications for the identification of molecular markers associated with CLA resistance. These markers can increase the accuracy and efficiency of aphid-resistant germplasm selection, ultimately facilitating the transfer of resistance traits to desirable wheat genotypes.
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Affiliation(s)
- Jayant Yadav
- ICAR- Indian Institute of Wheat and Barley Research, Karnal, Haryana, India
- CCS Haryana Agricultural University, Hisar, Haryana, India
| | - Poonam Jasrotia
- ICAR- Indian Institute of Wheat and Barley Research, Karnal, Haryana, India
| | | | - Sindhu Sareen
- ICAR- Indian Institute of Wheat and Barley Research, Karnal, Haryana, India
| | - Prem Lal Kashyap
- ICAR- Indian Institute of Wheat and Barley Research, Karnal, Haryana, India
| | - Sudheer Kumar
- ICAR- Indian Institute of Wheat and Barley Research, Karnal, Haryana, India
| | | | - Gyanendra Singh
- ICAR- Indian Institute of Wheat and Barley Research, Karnal, Haryana, India
| | - Gyanendra Pratap Singh
- ICAR- Indian Institute of Wheat and Barley Research, Karnal, Haryana, India
- ICAR- National Bureau of Plant Genetic Resources, New Delhi, India
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6
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Park MS, Lee S, Baek Y, Lee J, Park SS, Cho JH, Jin HJ, Yoo HR. Characteristics of insulin resistance in Korean adults from the perspective of circadian and metabolic sensing genes. Genes Genomics 2023; 45:1475-1487. [PMID: 37768516 PMCID: PMC10682234 DOI: 10.1007/s13258-023-01443-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2022] [Accepted: 08/20/2022] [Indexed: 09/29/2023]
Abstract
BACKGROUND The biological clock allows an organism to anticipate periodic environmental changes and adjust its physiology and behavior accordingly. OBJECTIVE This retrospective cross-sectional study examined circadian gene polymorphisms and clinical characteristics associated with insulin resistance (IR). METHODS We analyzed data from 1,404 Korean adults aged 30 to 55 with no history of cancer and cardio-cerebrovascular disease. The population was classified according to sex and homeostasis model assessment of insulin resistance (HOMA-IR) values. Demographics, anthropometric and clinical characteristics, and single nucleotide polymorphisms (SNPs) were analyzed with respect to sex, age, and HOMA-IR values. We used association rule mining to identify sets of SNPs from circadian and metabolic sensing genes that may be associated with IR. RESULTS Among the subjects, 15.0% of 960 women and 24.3% of 444 men had HOMA-IR values above 2. Most of the parameters differed significantly between men and women, as well as between the groups with high and low insulin sensitivity. Body fat mass of the trunk, which was significantly higher in insulin-resistant groups, had a higher correlation with high sensitivity C-reactive protein and hemoglobin levels in women, and alanine aminotransferase and aspartate aminotransferase levels in men. Homozygous minor allele genotype sets of SNPs rs17031578 and rs228669 in the PER3 gene could be more frequently found among women with HOMA-IR values above 2 (p = .014). CONCLUSION Oxidative stress enhanced by adiposity and iron overload, which may also be linked to NRF2 and PER3-related pathways, is related to IR in adulthood. However, due to the small population size in this study, more research is needed.
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Affiliation(s)
- Miso S Park
- Clinical Trial Center, Daejeon Korean Medicine Hospital of Daejeon University, 75 Daedeok-daero 176beon-gil, Seo- gu, Daejeon, 35235, Korea.
- Department of Cardiology and Neurology of Korean Medicine, College of Korean Medicine, Daejeon University, Daejeon, Korea.
| | - Siwoo Lee
- KM Data Division, Korea Institute of Oriental Medicine, 1672 Yuseong-daero, Yuseong-gu, Daejeon, 34054, Korea
| | - Younghwa Baek
- KM Data Division, Korea Institute of Oriental Medicine, 1672 Yuseong-daero, Yuseong-gu, Daejeon, 34054, Korea
| | - Juho Lee
- Data Convergence Drug Research Center, Korea Research Institute of Chemical Technology, University of Science & Technology, Daejeon, Korea
| | - Sang-Soo Park
- Clinical Trial Center, Daejeon Korean Medicine Hospital of Daejeon University, 75 Daedeok-daero 176beon-gil, Seo- gu, Daejeon, 35235, Korea
| | - Jung-Hyo Cho
- Liver and Immunology Research Center, Daejeon Korean Medicine Hospital of Daejeon University, Daejeon, Korea
| | - Hee-Jeong Jin
- KM Data Division, Korea Institute of Oriental Medicine, 1672 Yuseong-daero, Yuseong-gu, Daejeon, 34054, Korea
| | - Ho-Ryong Yoo
- Clinical Trial Center, Daejeon Korean Medicine Hospital of Daejeon University, 75 Daedeok-daero 176beon-gil, Seo- gu, Daejeon, 35235, Korea
- Department of Cardiology and Neurology of Korean Medicine, College of Korean Medicine, Daejeon University, Daejeon, Korea
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Warburton CL, Costilla R, Engle BN, Moore SS, Corbet NJ, Fordyce G, McGowan MR, Burns BM, Hayes BJ. Concurrently mapping quantitative trait loci associations from multiple subspecies within hybrid populations. Heredity (Edinb) 2023; 131:350-360. [PMID: 37798326 PMCID: PMC10673866 DOI: 10.1038/s41437-023-00651-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2022] [Revised: 09/19/2023] [Accepted: 09/21/2023] [Indexed: 10/07/2023] Open
Abstract
Many of the world's agriculturally important plant and animal populations consist of hybrids of subspecies. Cattle in tropical and sub-tropical regions for example, originate from two subspecies, Bos taurus indicus (Bos indicus) and Bos taurus taurus (Bos taurus). Methods to derive the underlying genetic architecture for these two subspecies are essential to develop accurate genomic predictions in these hybrid populations. We propose a novel method to achieve this. First, we use haplotypes to assign SNP alleles to ancestral subspecies of origin in a multi-breed and multi-subspecies population. Then we use a BayesR framework to allow SNP alleles originating from the different subspecies differing effects. Applying this method in a composite population of B. indicus and B. taurus hybrids, our results show that there are underlying genomic differences between the two subspecies, and these effects are not identified in multi-breed genomic evaluations that do not account for subspecies of origin effects. The method slightly improved the accuracy of genomic prediction. More significantly, by allocating SNP alleles to ancestral subspecies of origin, we were able to identify four SNP with high posterior probabilities of inclusion that have not been previously associated with cattle fertility and were close to genes associated with fertility in other species. These results show that haplotypes can be used to trace subspecies of origin through the genome of this hybrid population and, in conjunction with our novel Bayesian analysis, subspecies SNP allele allocation can be used to increase the accuracy of QTL association mapping in genetically diverse populations.
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Affiliation(s)
- Christie L Warburton
- Centre for Animal Science, Queensland Alliance for Agriculture and Food Innovation, University of Queensland, St. Lucia, QLD, Australia.
| | - Roy Costilla
- Agresearch Limited, Ruakura Research Centre, Hamilton, 3214, New Zealand
| | - Bailey N Engle
- Centre for Animal Science, Queensland Alliance for Agriculture and Food Innovation, University of Queensland, St. Lucia, QLD, Australia
| | - Stephen S Moore
- Centre for Animal Science, Queensland Alliance for Agriculture and Food Innovation, University of Queensland, St. Lucia, QLD, Australia
| | - Nicholas J Corbet
- Formerly Central Queensland University, School of Health, Medical and Applied Sciences, Rockhampton, QLD, Australia
| | - Geoffry Fordyce
- Centre for Animal Science, Queensland Alliance for Agriculture and Food Innovation, University of Queensland, St. Lucia, QLD, Australia
| | - Michael R McGowan
- The University of Queensland, School of Veterinary Science, St Lucia, QLD, Australia
| | - Brian M Burns
- Formerly Department of Agriculture and Fisheries, Rockhampton, QLD, Australia
| | - Ben J Hayes
- Centre for Animal Science, Queensland Alliance for Agriculture and Food Innovation, University of Queensland, St. Lucia, QLD, Australia
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8
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Genome-Wide Association Study for Grain Protein, Thousand Kernel Weight, and Normalized Difference Vegetation Index in Bread Wheat (Triticum aestivum L.). Genes (Basel) 2023; 14:genes14030637. [PMID: 36980909 PMCID: PMC10048783 DOI: 10.3390/genes14030637] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2023] [Revised: 02/24/2023] [Accepted: 02/28/2023] [Indexed: 03/08/2023] Open
Abstract
Genomic regions governing grain protein content (GPC), 1000 kernel weight (TKW), and normalized difference vegetation index (NDVI) were studied in a set of 280 bread wheat genotypes. The genome-wide association (GWAS) panel was genotyped using a 35K Axiom array and phenotyped in three environments. A total of 26 marker-trait associations (MTAs) were detected on 18 chromosomes covering the A, B, and D subgenomes of bread wheat. The GPC showed the maximum MTAs (16), followed by NDVI (6), and TKW (4). A maximum of 10 MTAs was located on the B subgenome, whereas, 8 MTAs each were mapped on the A and D subgenomes. In silico analysis suggest that the SNPs were located on important putative candidate genes such as NAC domain superfamily, zinc finger RING-H2-type, aspartic peptidase domain, folylpolyglutamate synthase, serine/threonine-protein kinase LRK10, pentatricopeptide repeat, protein kinase-like domain superfamily, cytochrome P450, and expansin. These candidate genes were found to have different roles including regulation of stress tolerance, nutrient remobilization, protein accumulation, nitrogen utilization, photosynthesis, grain filling, mitochondrial function, and kernel development. The effects of newly identified MTAs will be validated in different genetic backgrounds for further utilization in marker-aided breeding.
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Arandhara VL, McClure CP, Tarr AW, Chappell S, Morgan K, Baumert TF, Irving WL, Ball JK. Scavenger receptor class B type I genetic variants associated with disease severity in chronic hepatitis C virus infection. J Med Virol 2023; 95:e28331. [PMID: 36415047 PMCID: PMC10100136 DOI: 10.1002/jmv.28331] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Revised: 11/15/2022] [Accepted: 11/20/2022] [Indexed: 11/24/2022]
Abstract
Analysis of host genetic polymorphisms is an increasingly important tool for understanding and predicting pathogenesis and treatment response of viral diseases. The gene locus of scavenger receptor class B type I (SR-BI), encoding a cell entry factor and receptor for hepatitis C virus (HCV), contains several genetic polymorphisms. We applied a probe extension assay to determine the frequency of six single nucleotide polymorphisms (SNPs) within the SR-BI gene locus in 374 individuals with history of HCV infection. In addition, SR-BI messenger RNA (mRNA) levels were analyzed in liver biopsy specimens of chronically infected HCV subjects. The rs5888 variant allele T was present at a higher frequency in subjects with advanced fibrosis (χ2 , p = 0.016) and after adjusting for age, duration of infection and alcohol intake as confounding factors. Haplotype analysis of SNP frequencies showed that a haplotype consisting of rs61932577 variant allele C and rs5888 variant allele T was associated with an increased risk of advanced liver fibrosis (defined by an Ishak score 4-6) (adjusted odds ratio 2.81; 95% confidence interval 1.06-7.46. p = 0.038). Carriers of the rs5888 variant allele T displayed reduced SR-BI mRNA expression in liver biopsy specimens. In conclusion the rs5888 polymorphism variant is associated with decreased SR-BI expression and an increased risk of development of advanced fibrosis in chronic HCV infection. These findings provide further evidence for a role of SR-BI in HCV pathogenesis and provides a genetic marker for prediction of those infected individuals at greater risk of developing severe disease.
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Affiliation(s)
- Victoria L Arandhara
- School of Life Sciences, The University of Nottingham, Queen's Medical Centre, Nottingham, UK
| | - Charles Patrick McClure
- School of Life Sciences, The University of Nottingham, Queen's Medical Centre, Nottingham, UK.,Wolfson Centre for Global Virus Research, The University of Nottingham, Queen's Medical Centre, Nottingha, UK.,NIHR Nottingham Biomedical Research Centre at the Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, UK
| | - Alexander W Tarr
- School of Life Sciences, The University of Nottingham, Queen's Medical Centre, Nottingham, UK.,Wolfson Centre for Global Virus Research, The University of Nottingham, Queen's Medical Centre, Nottingha, UK.,NIHR Nottingham Biomedical Research Centre at the Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, UK
| | - Sally Chappell
- School of Life Sciences, The University of Nottingham, Queen's Medical Centre, Nottingham, UK
| | - Kevin Morgan
- School of Life Sciences, The University of Nottingham, Queen's Medical Centre, Nottingham, UK
| | - Thomas F Baumert
- Institut de Recherche sur les Maladies Virales et Hépatiques, Université de Strasbourg, Inserm, Strasbourg, France.,IHU Strasbourg, Pôle hépato-digestif, Hôpitaux Universitaires de Strasbourg, Strasbourg, France
| | - William L Irving
- School of Life Sciences, The University of Nottingham, Queen's Medical Centre, Nottingham, UK.,Wolfson Centre for Global Virus Research, The University of Nottingham, Queen's Medical Centre, Nottingha, UK.,NIHR Nottingham Biomedical Research Centre at the Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, UK
| | - Jonathan K Ball
- School of Life Sciences, The University of Nottingham, Queen's Medical Centre, Nottingham, UK.,Wolfson Centre for Global Virus Research, The University of Nottingham, Queen's Medical Centre, Nottingha, UK.,NIHR Nottingham Biomedical Research Centre at the Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, UK
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Li H, Wang Z, Xu L, Li Q, Gao H, Ma H, Cai W, Chen Y, Gao X, Zhang L, Gao H, Zhu B, Xu L, Li J. Genomic prediction of carcass traits using different haplotype block partitioning methods in beef cattle. Evol Appl 2022; 15:2028-2042. [PMID: 36540636 PMCID: PMC9753827 DOI: 10.1111/eva.13491] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2022] [Accepted: 09/18/2022] [Indexed: 09/22/2023] Open
Abstract
Genomic prediction (GP) based on haplotype alleles can capture quantitative trait loci (QTL) effects and increase predictive ability because the haplotypes are expected to be in linkage disequilibrium (LD) with QTL. In this study, we constructed haploblocks using LD-based and the fixed number of single nucleotide polymorphisms (fixed-SNP) methods with Illumina BovineHD chip in beef cattle. To evaluate the performance of different haplotype block partitioning methods, we constructed haploblocks based on LD thresholds (from r 2 > 0.2 to r 2 > 0.8) and the number of fixed-SNPs (5, 10, 20). The performance of predictive methods for three carcass traits including liveweight (LW), dressing percentage (DP), and longissimus dorsi muscle weight (LDMW) was evaluated using three approaches (GBLUP and BayesB model based on the SNP, GHBLUP, and BayesBH models based on the haploblock, and GHBLUP+GBLUP and BayesBH+BayesB models based on the combined haploblock and the nonblocked SNPs, which were located between blocks). In this study, we found the accuracies of LD-based and fixed-SNP haplotype Bayesian methods outperformed the Bayesian models (up to 8.54 ± 7.44% and 5.74 ± 2.95%, respectively). GHBLUP showed a high improvement (up to 11.29 ± 9.87%) compared with GBLUP. The Bayesian models have higher accuracies than BLUP models in most scenarios. The average computing time of the BayesBH+BayesB model can reduce by 29.3% compared with the BayesB model. The prediction accuracies using the LD-based haplotype method showed higher improvements than the fixed-SNP haplotype method. In addition, to avoid the influence of rare haplotypes generated from haplotype construction, we compared the performance of GP by filtering four types of minor haplotype allele frequency (MHAF) (0.01, 0.025, 0.05, and 0.1) under different conditions (LD levels were set at r 2 > 0.3, and the fixed number of SNPs was 5). We found the optimal MHAF threshold for LW was 0.01, and the optimal MHAF threshold for DP and LDMW was 0.025.
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Affiliation(s)
- Hongwei Li
- Laboratory of Molecular Biology and Bovine Breeding, Institute of Animal SciencesChinese Academy of Agricultural SciencesBeijingChina
| | - Zezhao Wang
- Laboratory of Molecular Biology and Bovine Breeding, Institute of Animal SciencesChinese Academy of Agricultural SciencesBeijingChina
| | - Lei Xu
- Laboratory of Molecular Biology and Bovine Breeding, Institute of Animal SciencesChinese Academy of Agricultural SciencesBeijingChina
| | - Qian Li
- Laboratory of Molecular Biology and Bovine Breeding, Institute of Animal SciencesChinese Academy of Agricultural SciencesBeijingChina
| | - Han Gao
- Laboratory of Molecular Biology and Bovine Breeding, Institute of Animal SciencesChinese Academy of Agricultural SciencesBeijingChina
| | - Haoran Ma
- Laboratory of Molecular Biology and Bovine Breeding, Institute of Animal SciencesChinese Academy of Agricultural SciencesBeijingChina
| | - Wentao Cai
- Laboratory of Molecular Biology and Bovine Breeding, Institute of Animal SciencesChinese Academy of Agricultural SciencesBeijingChina
| | - Yan Chen
- Laboratory of Molecular Biology and Bovine Breeding, Institute of Animal SciencesChinese Academy of Agricultural SciencesBeijingChina
| | - Xue Gao
- Laboratory of Molecular Biology and Bovine Breeding, Institute of Animal SciencesChinese Academy of Agricultural SciencesBeijingChina
| | - Lupei Zhang
- Laboratory of Molecular Biology and Bovine Breeding, Institute of Animal SciencesChinese Academy of Agricultural SciencesBeijingChina
| | - Huijiang Gao
- Laboratory of Molecular Biology and Bovine Breeding, Institute of Animal SciencesChinese Academy of Agricultural SciencesBeijingChina
| | - Bo Zhu
- Laboratory of Molecular Biology and Bovine Breeding, Institute of Animal SciencesChinese Academy of Agricultural SciencesBeijingChina
| | - Lingyang Xu
- Laboratory of Molecular Biology and Bovine Breeding, Institute of Animal SciencesChinese Academy of Agricultural SciencesBeijingChina
| | - Junya Li
- Laboratory of Molecular Biology and Bovine Breeding, Institute of Animal SciencesChinese Academy of Agricultural SciencesBeijingChina
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11
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Genetic dissection of grain iron and zinc, and thousand kernel weight in wheat (Triticum aestivum L.) using genome-wide association study. Sci Rep 2022; 12:12444. [PMID: 35858934 PMCID: PMC9300641 DOI: 10.1038/s41598-022-15992-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2022] [Accepted: 07/04/2022] [Indexed: 01/13/2023] Open
Abstract
Genetic biofortification is recognized as a cost-effective and sustainable strategy to reduce micronutrient malnutrition. Genomic regions governing grain iron concentration (GFeC), grain zinc concentration (GZnC), and thousand kernel weight (TKW) were investigated in a set of 280 diverse bread wheat genotypes. The genome-wide association (GWAS) panel was genotyped using 35 K Axiom Array and phenotyped in five environments. The GWAS analysis showed a total of 17 Bonferroni-corrected marker-trait associations (MTAs) in nine chromosomes representing all the three wheat subgenomes. The TKW showed the highest MTAs (7), followed by GZnC (5) and GFeC (5). Furthermore, 14 MTAs were identified with more than 10% phenotypic variation. One stable MTA i.e. AX-95025823 was identified for TKW in both E4 and E5 environments along with pooled data, which is located at 68.9 Mb on 6A chromosome. In silico analysis revealed that the SNPs were located on important putative candidate genes such as Multi antimicrobial extrusion protein, F-box domain, Late embryogenesis abundant protein, LEA-18, Leucine-rich repeat domain superfamily, and C3H4 type zinc finger protein, involved in iron translocation, iron and zinc homeostasis, and grain size modifications. The identified novel MTAs will be validated to estimate their effects in different genetic backgrounds for subsequent use in marker-assisted selection. The identified SNPs will be valuable in the rapid development of biofortified wheat varieties to ameliorate the malnutrition problems.
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Rajabi F, Jabalameli N, Rezaei N. The Concept of Immunogenetics. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2022; 1367:1-17. [DOI: 10.1007/978-3-030-92616-8_1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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13
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Further insight into the global variability of the OCA2-HERC2 locus for human pigmentation from multiallelic markers. Sci Rep 2021; 11:22530. [PMID: 34795370 PMCID: PMC8602267 DOI: 10.1038/s41598-021-01940-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Accepted: 11/02/2021] [Indexed: 11/20/2022] Open
Abstract
The OCA2-HERC2 locus is responsible for the greatest proportion of eye color variation in humans. Numerous studies extensively described both functional SNPs and associated patterns of variation over this region. The goal of our study is to examine how these haplotype structures and allelic associations vary when highly variable markers such as microsatellites are used. Eleven microsatellites spanning 357 Kb of OCA2-HERC2 genes are analyzed in 3029 individuals from worldwide populations. We found that several markers display large differences in allele frequency (10% to 35% difference) among Europeans, East Asians and Africans. In Europe, the alleles showing increased frequency can also discriminate individuals with (IrisPlex) predicted blue and brown eyes. Distinct haplotypes are identified around the variants C and T of the functional SNP rs12913832 (associated to blue eyes), with linkage disequilibrium r2 values significant up to 237 Kb. The haplotype carrying the allele rs12913832 C has high frequency (76%) in blue eye predicted individuals (30% in brown eye predicted individuals), while the haplotype associated to the allele rs12913832 T is restricted to brown eye predicted individuals. Finally, homozygosity values reach levels of 91% near rs12913832. Odds ratios show values of 4.2, 7.4 and 10.4 for four markers around rs12913832 and 7.1 for their core haplotype. Hence, this study provides an example on the informativeness of multiallelic markers that, despite their current limited potential contribution to forensic eye color prediction, supports the use of microsatellites for identifying causing variants showing similar genetic features and history.
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Li H, Zhu B, Xu L, Wang Z, Xu L, Zhou P, Gao H, Guo P, Chen Y, Gao X, Zhang L, Gao H, Cai W, Xu L, Li J. Genomic Prediction Using LD-Based Haplotypes Inferred From High-Density Chip and Imputed Sequence Variants in Chinese Simmental Beef Cattle. Front Genet 2021; 12:665382. [PMID: 34394182 PMCID: PMC8358323 DOI: 10.3389/fgene.2021.665382] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2021] [Accepted: 06/30/2021] [Indexed: 01/05/2023] Open
Abstract
A haplotype is defined as a combination of alleles at adjacent loci belonging to the same chromosome that can be transmitted as a unit. In this study, we used both the Illumina BovineHD chip (HD chip) and imputed whole-genome sequence (WGS) data to explore haploblocks and assess haplotype effects, and the haploblocks were defined based on the different LD thresholds. The accuracies of genomic prediction (GP) for dressing percentage (DP), meat percentage (MP), and rib eye roll weight (RERW) based on haplotype were investigated and compared for both data sets in Chinese Simmental beef cattle. The accuracies of GP using the entire imputed WGS data were lower than those using the HD chip data in all cases. For DP and MP, the accuracy of GP using haploblock approaches outperformed the individual single nucleotide polymorphism (SNP) approach (GBLUP_In_Block) at specific LD levels. Hotelling’s test confirmed that GP using LD-based haplotypes from WGS data can significantly increase the accuracies of GP for RERW, compared with the individual SNP approach (∼1.4 and 1.9% for GHBLUP and GHBLUP+GBLUP, respectively). We found that the accuracies using haploblock approach varied with different LD thresholds. The LD thresholds (r2 ≥ 0.5) were optimal for most scenarios. Our results suggested that LD-based haploblock approach can improve accuracy of genomic prediction for carcass traits using both HD chip and imputed WGS data under the optimal LD thresholds in Chinese Simmental beef cattle.
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Affiliation(s)
- Hongwei Li
- Laboratory of Molecular Biology and Bovine Breeding, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, China
| | - Bo Zhu
- Laboratory of Molecular Biology and Bovine Breeding, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, China.,National Centre of Beef Cattle Genetic Evaluation, Beijing, China
| | - Ling Xu
- Laboratory of Molecular Biology and Bovine Breeding, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, China
| | - Zezhao Wang
- Laboratory of Molecular Biology and Bovine Breeding, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, China
| | - Lei Xu
- Laboratory of Molecular Biology and Bovine Breeding, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, China
| | - Peinuo Zhou
- Laboratory of Molecular Biology and Bovine Breeding, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, China
| | - Han Gao
- Laboratory of Molecular Biology and Bovine Breeding, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, China
| | - Peng Guo
- College of Computer and Information Engineering, Tianjin Agricultural University, Tianjin, China
| | - Yan Chen
- Laboratory of Molecular Biology and Bovine Breeding, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, China
| | - Xue Gao
- Laboratory of Molecular Biology and Bovine Breeding, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, China
| | - Lupei Zhang
- Laboratory of Molecular Biology and Bovine Breeding, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, China
| | - Huijiang Gao
- Laboratory of Molecular Biology and Bovine Breeding, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, China.,National Centre of Beef Cattle Genetic Evaluation, Beijing, China
| | - Wentao Cai
- Laboratory of Molecular Biology and Bovine Breeding, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, China
| | - Lingyang Xu
- Laboratory of Molecular Biology and Bovine Breeding, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, China
| | - Junya Li
- Laboratory of Molecular Biology and Bovine Breeding, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, China.,National Centre of Beef Cattle Genetic Evaluation, Beijing, China
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15
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Sharifi RS, Noshahr FA, Seifdavati J, Evrigh NH, Cipriano-Salazar M, Mariezcurrena-Berasain MA. Comparison of haplotype method using for genomic prediction versus single SNP genotypes in sheep breeding programs. Small Rumin Res 2021. [DOI: 10.1016/j.smallrumres.2021.106380] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
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16
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Pieters A, Gijbels E, Cogliati B, Annaert P, Devisscher L, Vinken M. Biomarkers of cholestasis. Biomark Med 2021; 15:437-454. [PMID: 33709780 DOI: 10.2217/bmm-2020-0691] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Cholestasis is a major pathological manifestation, often resulting in detrimental liver conditions, which occurs in a variety of indications collectively termed cholestatic liver diseases. The frequent asymptomatic character and complexity of cholestasis, together with the lack of a straightforward biomarker, hampers early detection and treatment of the condition. The 'omics' era, however, has resulted in a plethora of cholestatic indicators, yet a single clinically applicable biomarker for a given cholestatic disease remains missing. The criteria to fulfil as an ideal biomarker as well as the challenging molecular pathways in cholestatic liver diseases advocate for a scenario in which multiple biomarkers, originating from different domains, will be assessed concomitantly. This review gives an overview of classical clinical and novel molecular biomarkers in cholestasis, focusing on their benefits and drawbacks.
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Affiliation(s)
- Alanah Pieters
- Department of In Vitro Toxicology & Dermato-Cosmetology, Vrije Universiteit Brussel, Laarbeeklaan 103, Brussels, 1090, Belgium
| | - Eva Gijbels
- Department of In Vitro Toxicology & Dermato-Cosmetology, Vrije Universiteit Brussel, Laarbeeklaan 103, Brussels, 1090, Belgium
| | - Bruno Cogliati
- Department of Pathology, School of Veterinary Medicine & Animal Science, University of São Paulo, Av. Prof. Dr. Orlando Marques de Paiva 87, Cidade Universitária, SP, 05508-270, Brazil
| | - Pieter Annaert
- Drug Delivery & Disposition, Department of Pharmaceutical & Pharmacological Sciences, Katholieke Universiteit Leuven, ON II Herestraat 49, Box 921, Leuven, 3000, Belgium
| | - Lindsey Devisscher
- Basic & Applied Medical Sciences, Gut-Liver Immunopharmacology Unit, Faculty of Medicine & Health Sciences, Ghent University, C Heymanslaan 10, Ghent, 9000, Belgium
| | - Mathieu Vinken
- Department of In Vitro Toxicology & Dermato-Cosmetology, Vrije Universiteit Brussel, Laarbeeklaan 103, Brussels, 1090, Belgium
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17
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Bernardino KC, de Menezes CB, de Sousa SM, Guimarães CT, Carneiro PCS, Schaffert RE, Kochian LV, Hufnagel B, Pastina MM, Magalhaes JV. Association mapping and genomic selection for sorghum adaptation to tropical soils of Brazil in a sorghum multiparental random mating population. TAG. THEORETICAL AND APPLIED GENETICS. THEORETISCHE UND ANGEWANDTE GENETIK 2021; 134:295-312. [PMID: 33052425 DOI: 10.1007/s00122-020-03697-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/17/2019] [Accepted: 09/28/2020] [Indexed: 06/11/2023]
Abstract
A multiparental random mating population used in sorghum breeding is amenable for the detection of QTLs related to tropical soil adaptation, fine mapping of underlying genes and genomic selection approaches. Tropical soils where low phosphorus (P) and aluminum (Al) toxicity limit sorghum [Sorghum bicolor (L.) Moench] production are widespread in the developing world. We report on BRP13R, a multiparental random mating population (MP-RMP), which is commonly used in sorghum recurrent selection targeting tropical soil adaptation. Recombination dissipated much of BRP13R's likely original population structure and average linkage disequilibrium (LD) persisted up to 2.5 Mb, establishing BRP13R as a middle ground between biparental populations and sorghum association panels. Genome-wide association mapping (GWAS) identified conserved QTL from previous studies, such as for root morphology and grain yield under low-P, and indicated the importance of dominance in the genetic architecture of grain yield. By overlapping consensus QTL regions, we mapped two candidate P efficiency genes to a ~ 5 Mb region on chromosomes 6 (ALMT) and 9 (PHO2). Remarkably, we find that only 200 progeny genotyped with ~ 45,000 markers in BRP13R can lead to GWAS-based positional cloning of naturally rare, subpopulation-specific alleles, such as for SbMATE-conditioned Al tolerance. Genomic selection was found to be useful in such MP-RMP, particularly if markers in LD with major genes are fitted as fixed effects into GBLUP models accommodating dominance. Shifts in allele frequencies in progeny contrasting for grain yield indicated that intermediate to minor-effect genes on P efficiency, such as SbPSTOL1 genes, can be employed in pre-breeding via allele mining in the base population. Therefore, MP-RMPs such as BRP13R emerge as multipurpose resources for efficient gene discovery and deployment for breeding sorghum cultivars adapted to tropical soils.
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Affiliation(s)
- Karine C Bernardino
- Universidade Federal de Viçosa, Avenida Peter Henry Rolfs, s/n, Viçosa, MG, 36570-900, Brazil
- Embrapa Milho e Sorgo, Rodovia MG 424 km 65, Sete Lagoas, MG, 35701-970, Brazil
| | - Cícero B de Menezes
- Embrapa Milho e Sorgo, Rodovia MG 424 km 65, Sete Lagoas, MG, 35701-970, Brazil
| | - Sylvia M de Sousa
- Embrapa Milho e Sorgo, Rodovia MG 424 km 65, Sete Lagoas, MG, 35701-970, Brazil
| | - Claudia T Guimarães
- Embrapa Milho e Sorgo, Rodovia MG 424 km 65, Sete Lagoas, MG, 35701-970, Brazil
| | - Pedro C S Carneiro
- Universidade Federal de Viçosa, Avenida Peter Henry Rolfs, s/n, Viçosa, MG, 36570-900, Brazil
| | - Robert E Schaffert
- Embrapa Milho e Sorgo, Rodovia MG 424 km 65, Sete Lagoas, MG, 35701-970, Brazil
| | - Leon V Kochian
- Global Institute for Food Security, University of Saskatchewan, Saskatoon, SK, S7N 4J8, Canada
| | - Barbara Hufnagel
- Embrapa Milho e Sorgo, Rodovia MG 424 km 65, Sete Lagoas, MG, 35701-970, Brazil
- BPMP, CNRS, INRAE, SupAgro, University of Montpellier, 34060, Montpellier, France
| | - Maria Marta Pastina
- Embrapa Milho e Sorgo, Rodovia MG 424 km 65, Sete Lagoas, MG, 35701-970, Brazil.
| | - Jurandir V Magalhaes
- Embrapa Milho e Sorgo, Rodovia MG 424 km 65, Sete Lagoas, MG, 35701-970, Brazil.
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18
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Gupta N, Zargar SM, Singh R, Nazir M, Mahajan R, Salgotra RK. Marker association study of yield attributing traits in common bean (Phaseolus vulgaris L.). Mol Biol Rep 2020; 47:6769-6783. [PMID: 32852680 DOI: 10.1007/s11033-020-05735-6] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2019] [Accepted: 08/20/2020] [Indexed: 01/20/2023]
Abstract
Common bean is gaining acceptance as one of the most valuable major food consumed worldwide owing to innumerable nutritional and therapeutic benefits. Comparatively less productivity in underdeveloped countries encouraged us to proceed for QTL mining of yield traits in common bean. Heretofore, multiple yield associated markers have been detected all over the world; even so, the present work is looked on as the first report on identification of novel/new potent markers by exploiting the germplasm of Northern India. A panel of one hundred and thirty five genotypes was used for morphological studies and based on preliminary molecular evaluation; a set of ninety six diverse common bean genotypes (core set) was selected for association analysis. Molecular data generated by a total of ninety eight microsatellite markers (53 genomic and 45 genic SSRs) revealed high estimation of polymorphism among the genotypes that were observed to be divided into two major sub-populations and varying levels of admixtures based on population structure analyses. By employing both MLM and GLM analysis approaches, we identified 46 and 16 significant marker-trait associations (p ≤ 0.005) respectively, few of which have already been reported and hence validate our results. PVBR213 marker was found to be strongly associated with days to bud initiation trait when analyzed with both the approaches. Phenotypic variation of identified significant markers ranged from 3.1% to 32.7% where PVBR87, PVBR213, X96999 and X57022 explain more than 30% of phenotypic variation for 100 seed weight, days to bud initiation, pods per plant and pod length traits respectively. These findings introduce highly informative markers to aid marker-assisted selection program in common bean for high yield performance along with good agronomic merit.
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Affiliation(s)
- Nancy Gupta
- School of Biotechnology, Sher-E-Kashmir University of Agricultural Sciences and Technology of Jammu, Chatha, Jammu, Jammu and Kashmir, 180009, India
| | - Sajad Majeed Zargar
- Proteomics Laboratory, Division of Plant Biotechnology, Sher-E-Kashmir University of Agricultural Sciences and Technology of Srinagar, Shalimar, Srinagar, Jammu and Kashmir, 190025, India.
| | - Ravinder Singh
- School of Biotechnology, Sher-E-Kashmir University of Agricultural Sciences and Technology of Jammu, Chatha, Jammu, Jammu and Kashmir, 180009, India
| | - Muslima Nazir
- Proteomics Laboratory, Division of Plant Biotechnology, Sher-E-Kashmir University of Agricultural Sciences and Technology of Srinagar, Shalimar, Srinagar, Jammu and Kashmir, 190025, India
| | - Reetika Mahajan
- Proteomics Laboratory, Division of Plant Biotechnology, Sher-E-Kashmir University of Agricultural Sciences and Technology of Srinagar, Shalimar, Srinagar, Jammu and Kashmir, 190025, India
| | - R K Salgotra
- School of Biotechnology, Sher-E-Kashmir University of Agricultural Sciences and Technology of Jammu, Chatha, Jammu, Jammu and Kashmir, 180009, India
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Habib M, Awan FS, Sadia B, Zia MA. Genome-Wide Association Mapping for Stripe Rust Resistance in Pakistani Spring Wheat Genotypes. PLANTS 2020; 9:plants9091056. [PMID: 32824927 PMCID: PMC7570266 DOI: 10.3390/plants9091056] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/13/2020] [Revised: 06/13/2020] [Accepted: 06/15/2020] [Indexed: 11/16/2022]
Abstract
Stripe rust caused by the pathogen Puccinia striiformis f. sp. tritici (Pst) is a major threat for wheat, resulting in low yield and grain quality loss in many countries. Genetic resistance is a prevalent method to combat the disease. Mapping the resistant loci and their association with traits is highly exploited in this era. A panel of 465 Pakistani spring wheat genotypes were evaluated for their phenotypic response to stripe rust at the seedling and adult plant stages. A total of 765 single nucleotide polymorphism (SNP) markers were applied on 465 wheat genotypes to evaluate their stripe rust response against nine races during the seedling test and in three locations for the field test. Currently, twenty SNPs dispersed on twelve chromosomal regions (1A, 1B, 1D, 2A, 2B, 4A, 4B, 5B, 6A, 6B, 6D and 7B) have been identified that were associated with rust race-specific resistance at the seedling stage. Thirty SNPs dispersed on eighteen chromosomal regions (1A, 1B, 1D, 2A, 2B, 2D, 3A, 3B, 3D, 4B, 5A, 5B, 6A, 6B, 6D, 7A, 7B and 7D) are associated with adult plant resistance. SNP loci IWB3662 was linked with all three Pakistani races, and likewise IWA2344 and IWA4096 were found to be linked with three different USA races. The present research findings can be applied by wheat breeders to increase their resistant capability and yield potential of their cultivars, through marker-assisted selection.
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Affiliation(s)
- Madiha Habib
- Centre of Agricultural Biochemistry and Biotechnology, University of Agriculture, Faisalabad 38000, Pakistan; (M.H.); (B.S.)
| | - Faisal Saeed Awan
- Centre of Agricultural Biochemistry and Biotechnology, University of Agriculture, Faisalabad 38000, Pakistan; (M.H.); (B.S.)
- Correspondence: ; Tel.: +92-41-9201087
| | - Bushra Sadia
- Centre of Agricultural Biochemistry and Biotechnology, University of Agriculture, Faisalabad 38000, Pakistan; (M.H.); (B.S.)
| | - Muhammad Anjum Zia
- Department of Biochemistry, University of Agriculture, Faisalabad 38000, Pakistan;
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20
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Hasenauer FC, Rossi UA, Caffaro ME, Raschia MA, Maurizio E, Poli MA, Rossetti CA. Association of TNF rs668920841 and INRA111 polymorphisms with caprine brucellosis: A case-control study of candidate genes involved in innate immunity. Genomics 2020; 112:3925-3932. [PMID: 32629097 DOI: 10.1016/j.ygeno.2020.06.050] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2020] [Revised: 05/25/2020] [Accepted: 06/28/2020] [Indexed: 01/24/2023]
Abstract
Caprine brucellosis is an infectious, contagious zoonotic disease caused by Brucella melitensis. Multiple factors, including host genetics, can influence the outcome of the exposure to Brucella; and it is expected that genetic variants that affect the host innate immune response could have a key role in Brucella infection and pathogenesis. In this study, we evaluated if polymorphisms in innate immunity-related genes are associated with results of Brucella infection in goats. Nine polymorphisms within interferon gamma (IFNG), tumor necrosis factor (TNF), MyD88 innate immune signal transduction adaptor (MYD88), interleukin 10 (IL10) and IL-10 receptor subunit alpha (IL10RA) genes and two molecular markers (BMS2753 and INRA111) were resolved by PCR-capillary electrophoresis in samples from 81 seronegative and 61 seropositive goats for brucellosis. A heterozygous genotype at INRA111, a microsatellite near the VRK serine/threonine kinase 2 (VRK2) gene, was associated with absence of Brucella-specific antibodies in goats naturally exposed to the pathogen (P = .004). Conversely, variants in the TNF gene (rs668920841) and near the IFN gamma receptor 1 (IFNGR1) gene (microsatellite BMS2753) were significantly associated with presence of Brucella-specific antibodies at allelic (P = .042 and P = .046) and genotypic level (P = .012 and P = .041, respectively). Moreover, an in silico analysis predicted a functional role of the insertion-deletion polymorphism rs668920841 on the transcriptional regulation of the caprine TNF gene. Altogether, these results contribute to the identification of genetic factors that have a putative effect on the resistance / susceptibility phenotype of goats to Brucella infection.
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Affiliation(s)
- F C Hasenauer
- Instituto de Patobiología, CICVyA, INTA, Nicolás Repetto y de Los Reseros s/n, Hurlingham, B1686, Buenos Aires, Argentina; CONICET, Godoy Cruz 2290, C1425 CABA, Argentina
| | - U A Rossi
- Instituto de Patobiología, CICVyA, INTA, Nicolás Repetto y de Los Reseros s/n, Hurlingham, B1686, Buenos Aires, Argentina; CONICET, Godoy Cruz 2290, C1425 CABA, Argentina
| | - M E Caffaro
- Instituto de Genética "Ewald A. Favret", CICVyA, INTA, Nicolás Repetto y de Los Reseros s/n, Hurlingham, B1686, Buenos Aires, Argentina
| | - M A Raschia
- Instituto de Genética "Ewald A. Favret", CICVyA, INTA, Nicolás Repetto y de Los Reseros s/n, Hurlingham, B1686, Buenos Aires, Argentina
| | - E Maurizio
- Instituto de Patobiología, CICVyA, INTA, Nicolás Repetto y de Los Reseros s/n, Hurlingham, B1686, Buenos Aires, Argentina; CONICET, Godoy Cruz 2290, C1425 CABA, Argentina
| | - M A Poli
- Instituto de Genética "Ewald A. Favret", CICVyA, INTA, Nicolás Repetto y de Los Reseros s/n, Hurlingham, B1686, Buenos Aires, Argentina
| | - C A Rossetti
- Instituto de Patobiología, CICVyA, INTA, Nicolás Repetto y de Los Reseros s/n, Hurlingham, B1686, Buenos Aires, Argentina.
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Blatt M, Gusev A, Polyakov Y, Goldwasser S. Secure large-scale genome-wide association studies using homomorphic encryption. Proc Natl Acad Sci U S A 2020; 117:11608-11613. [PMID: 32398369 PMCID: PMC7261120 DOI: 10.1073/pnas.1918257117] [Citation(s) in RCA: 38] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023] Open
Abstract
Genome-wide association studies (GWASs) seek to identify genetic variants associated with a trait, and have been a powerful approach for understanding complex diseases. A critical challenge for GWASs has been the dependence on individual-level data that typically have strict privacy requirements, creating an urgent need for methods that preserve the individual-level privacy of participants. Here, we present a privacy-preserving framework based on several advances in homomorphic encryption and demonstrate that it can perform an accurate GWAS analysis for a real dataset of more than 25,000 individuals, keeping all individual data encrypted and requiring no user interactions. Our extrapolations show that it can evaluate GWASs of 100,000 individuals and 500,000 single-nucleotide polymorphisms (SNPs) in 5.6 h on a single server node (or in 11 min on 31 server nodes running in parallel). Our performance results are more than one order of magnitude faster than prior state-of-the-art results using secure multiparty computation, which requires continuous user interactions, with the accuracy of both solutions being similar. Our homomorphic encryption advances can also be applied to other domains where large-scale statistical analyses over encrypted data are needed.
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Affiliation(s)
| | - Alexander Gusev
- Duality Technologies, Inc., Newark, NJ 07103
- Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215
| | | | - Shafi Goldwasser
- Duality Technologies, Inc., Newark, NJ 07103;
- Simons Institute for the Theory of Computing, University of California, Berkeley, CA 94720
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22
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Zhou Z, Shi X, Zhao G, Qin M, Ibba MI, Wang Y, Li W, Yang P, Wu Z, Lei Z, Wang J. Identification of Novel Genomic Regions and Superior Alleles Associated with Zn Accumulation in Wheat Using a Genome-Wide Association Analysis Method. Int J Mol Sci 2020; 21:ijms21061928. [PMID: 32168957 PMCID: PMC7139793 DOI: 10.3390/ijms21061928] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2020] [Revised: 03/07/2020] [Accepted: 03/09/2020] [Indexed: 12/24/2022] Open
Abstract
Micronutrient deficiencies, and especially zinc (Zn) deficiency, pose serious health problems to people who mainly depend on cereal-based diets. Here, we performed a genome-wide association study (GWAS) to detect the genetic basis of the Zn accumulation in wheat (Triticum aestivum L.) grains with a diversity panel of 207 bread wheat varieties. To uncover authentic quantitative trait loci (QTL) controlling Zn accumulation, the varieties were planted in three locations. In total, 29 unique loci associated with Zn grain accumulation were identified. Notably, seven non-redundant loci located on chromosomes 1B, 3B, 3D, 4A, 5A, 5B, and 7A, were detected at least in two environments. Of these quantitative trait loci (QTL), six coincided with known QTL or genes, whereas the highest effect QTL on chromosome 3D identified in this study was not reported previously. Searches of public databases revealed that the seven identified QTL coincided with seven putative candidate genes linked to Zn accumulation. Among these seven genes, NAC domain-containing protein gene (TraesCS3D02G078500) linked with the most significant single nucleotide polymorphism (SNP) AX-94729264 on chromosome 3D was relevant to metal accumulation in wheat grains. Results of this study provide new insights into the genetic architecture of Zn accumulation in wheat grains.
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Affiliation(s)
- Zhengfu Zhou
- Wheat Research Institute, Henan Academy of Agricultural Sciences, Zhengzhou 450002, China; (Z.Z.); (X.S.); (M.Q.); (Y.W.); (W.L.); (P.Y.); (Z.W.)
| | - Xia Shi
- Wheat Research Institute, Henan Academy of Agricultural Sciences, Zhengzhou 450002, China; (Z.Z.); (X.S.); (M.Q.); (Y.W.); (W.L.); (P.Y.); (Z.W.)
| | - Ganqing Zhao
- College of Chemistry and Environment Engineering, Pingdingshan University, Pingdingshan 467000, China;
| | - Maomao Qin
- Wheat Research Institute, Henan Academy of Agricultural Sciences, Zhengzhou 450002, China; (Z.Z.); (X.S.); (M.Q.); (Y.W.); (W.L.); (P.Y.); (Z.W.)
| | - Maria Itria Ibba
- Global Wheat Program, International Maize and Wheat Improvement Center (CIMMYT), Mexico, D.F. 06600, Mexico;
| | - Yahuan Wang
- Wheat Research Institute, Henan Academy of Agricultural Sciences, Zhengzhou 450002, China; (Z.Z.); (X.S.); (M.Q.); (Y.W.); (W.L.); (P.Y.); (Z.W.)
| | - Wenxu Li
- Wheat Research Institute, Henan Academy of Agricultural Sciences, Zhengzhou 450002, China; (Z.Z.); (X.S.); (M.Q.); (Y.W.); (W.L.); (P.Y.); (Z.W.)
| | - Pan Yang
- Wheat Research Institute, Henan Academy of Agricultural Sciences, Zhengzhou 450002, China; (Z.Z.); (X.S.); (M.Q.); (Y.W.); (W.L.); (P.Y.); (Z.W.)
| | - Zhengqing Wu
- Wheat Research Institute, Henan Academy of Agricultural Sciences, Zhengzhou 450002, China; (Z.Z.); (X.S.); (M.Q.); (Y.W.); (W.L.); (P.Y.); (Z.W.)
- College of Life Sciences, Zhengzhou University, Zhengzhou 450001, China
| | - Zhensheng Lei
- Wheat Research Institute, Henan Academy of Agricultural Sciences, Zhengzhou 450002, China; (Z.Z.); (X.S.); (M.Q.); (Y.W.); (W.L.); (P.Y.); (Z.W.)
- College of Chemistry and Environment Engineering, Pingdingshan University, Pingdingshan 467000, China;
- College of Life Sciences, Zhengzhou University, Zhengzhou 450001, China
- Correspondence: (Z.L.); (J.W.); Tel.: +86-371-6572-4084 (Z.L.); +86-158-3759-0332 (J.W.)
| | - Jiansheng Wang
- College of Chemistry and Environment Engineering, Pingdingshan University, Pingdingshan 467000, China;
- Correspondence: (Z.L.); (J.W.); Tel.: +86-371-6572-4084 (Z.L.); +86-158-3759-0332 (J.W.)
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23
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Dennison CA, Legge SE, Pardiñas AF, Walters JTR. Genome-wide association studies in schizophrenia: Recent advances, challenges and future perspective. Schizophr Res 2020; 217:4-12. [PMID: 31780348 DOI: 10.1016/j.schres.2019.10.048] [Citation(s) in RCA: 44] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2019] [Accepted: 10/24/2019] [Indexed: 01/07/2023]
Abstract
Genome-wide association studies (GWAS) have proved to be a powerful approach for gene discovery in schizophrenia; their findings have important implications not just for our understanding of the genetic architecture of the disorder, but for the potential applications of personalised medicine through improved classification and targeted interventions. In this article we review the current status of the GWAS literature in schizophrenia including functional annotation methods and polygenic risk scoring, as well as the directions and challenges of future research. We consider recent findings in East Asian populations and the advancements from trans-ancestry analysis, as well as the insights gained from research looking across psychiatric disorders.
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Affiliation(s)
- Charlotte A Dennison
- MRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, UK
| | - Sophie E Legge
- MRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, UK
| | - Antonio F Pardiñas
- MRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, UK
| | - James T R Walters
- MRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, UK.
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24
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Laganà AS, Garzon S, Götte M, Viganò P, Franchi M, Ghezzi F, Martin DC. The Pathogenesis of Endometriosis: Molecular and Cell Biology Insights. Int J Mol Sci 2019; 20:E5615. [PMID: 31717614 PMCID: PMC6888544 DOI: 10.3390/ijms20225615] [Citation(s) in RCA: 265] [Impact Index Per Article: 44.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2019] [Revised: 11/01/2019] [Accepted: 11/07/2019] [Indexed: 12/15/2022] Open
Abstract
The etiopathogenesis of endometriosis is a multifactorial process resulting in a heterogeneous disease. Considering that endometriosis etiology and pathogenesis are still far from being fully elucidated, the current review aims to offer a comprehensive summary of the available evidence. We performed a narrative review synthesizing the findings of the English literature retrieved from computerized databases from inception to June 2019, using the Medical Subject Headings (MeSH) unique ID term "Endometriosis" (ID:D004715) with "Etiology" (ID:Q000209), "Immunology" (ID:Q000276), "Genetics" (ID:D005823) and "Epigenesis, Genetic" (ID:D044127). Endometriosis may origin from Müllerian or non-Müllerian stem cells including those from the endometrial basal layer, Müllerian remnants, bone marrow, or the peritoneum. The innate ability of endometrial stem cells to regenerate cyclically seems to play a key role, as well as the dysregulated hormonal pathways. The presence of such cells in the peritoneal cavity and what leads to the development of endometriosis is a complex process with a large number of interconnected factors, potentially both inherited and acquired. Genetic predisposition is complex and related to the combined action of several genes with limited influence. The epigenetic mechanisms control many of the processes involved in the immunologic, immunohistochemical, histological, and biological aberrations that characterize the eutopic and ectopic endometrium in affected patients. However, what triggers such alterations is not clear and may be both genetically and epigenetically inherited, or it may be acquired by the particular combination of several elements such as the persistent peritoneal menstrual reflux as well as exogenous factors. The heterogeneity of endometriosis and the different contexts in which it develops suggest that a single etiopathogenetic model is not sufficient to explain its complex pathobiology.
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Affiliation(s)
- Antonio Simone Laganà
- Department of Obstetrics and Gynecology, “Filippo Del Ponte” Hospital, University of Insubria, Piazza Biroldi 1, 21100 Varese, Italy; (S.G.); (F.G.)
| | - Simone Garzon
- Department of Obstetrics and Gynecology, “Filippo Del Ponte” Hospital, University of Insubria, Piazza Biroldi 1, 21100 Varese, Italy; (S.G.); (F.G.)
| | - Martin Götte
- Department of Gynecology and Obstetrics, Münster University Hospital, D-48149 Münster, Germany;
| | - Paola Viganò
- Reproductive Sciences Laboratory, Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Via Olgettina 60, 20136 Milan, Italy;
| | - Massimo Franchi
- Department of Obstetrics and Gynecology, AOUI Verona, University of Verona, Piazzale Aristide Stefani 1, 37126 Verona, Italy;
| | - Fabio Ghezzi
- Department of Obstetrics and Gynecology, “Filippo Del Ponte” Hospital, University of Insubria, Piazza Biroldi 1, 21100 Varese, Italy; (S.G.); (F.G.)
| | - Dan C. Martin
- School of Medicine, University of Tennessee Health Science Center, 910 Madison Ave, Memphis, TN 38163, USA;
- Virginia Commonwealth University, 907 Floyd Ave, Richmond, VA 23284, USA
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25
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Tardivel A, Torkamaneh D, Lemay MA, Belzile F, O'Donoughue LS. A Systematic Gene-Centric Approach to Define Haplotypes and Identify Alleles on the Basis of Dense Single Nucleotide Polymorphism Datasets. THE PLANT GENOME 2019; 12:1-11. [PMID: 33016581 DOI: 10.3835/plantgenome2018.08.0061] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/28/2018] [Accepted: 04/01/2019] [Indexed: 05/15/2023]
Abstract
A gene-centric approach for haplotype definition was developed and implemented in R. The tool allows for allelic characterization at given loci in germplasm collections. Allelic status at four maturity genes is predicted on the basis of marker genotyping data. Assessing the allelic diversity within a germplasm collection and identifying individuals carrying favorable alleles is challenging. Advances in high-throughput technologies allow the genotyping of many individuals for thousands of markers but bridging the gap between single nucleotide polymorphisms (SNPs) and relevant alleles remains difficult. We developed a systematic approach that defines haplotypes from large SNP catalogs that aims to identify haplotypes that can be equated to alleles at given genes. Unlike haplotype visualization tools, our approach selects SNP markers that flank a gene and define haplotypes that correspond to this gene's alleles. We tested this approach on four known soybean [Glycine max (L.) Merr.] maturity genes (E1, GmGia, GmPhyA3, and GmPhyA2) in a collection of 67 lines and two genotypic datasets [a SNP array and genotyping-by-sequencing (GBS)]. For E1, GmGia, and GmPhyA3, we identified SNP haplotypes such that the allele found at these genes could be accurately predicted from the haplotype in 97.3% of the cases. For these genes, of the 12 known alleles in the collection, 10 and 8 could be correctly predicted from the haplotypes found with the SNP array and GBS datasets, with success rates of 98 and 97% for all allele-line combinations, respectively. The approach proved equally successful for data derived from a SNP array and GBS. However, in the case of GmPhyA2, a lack of markers in the genomic region prevented the identification of alleles, regardless of the dataset. We demonstrate the feasibility and reproducibility of our approach and identify limits to its applicability.
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Affiliation(s)
- Aurélie Tardivel
- Dép. de Phytologie and Institut de Biologie Intégrative et des Systèmes, Univ. Laval, Quebec City, QC, Canada, G1V 0A6
| | - Davoud Torkamaneh
- Dép. de Phytologie and Institut de Biologie Intégrative et des Systèmes, Univ. Laval, Quebec City, QC, Canada, G1V 0A6
| | - Marc-André Lemay
- Dép. de Phytologie and Institut de Biologie Intégrative et des Systèmes, Univ. Laval, Quebec City, QC, Canada, G1V 0A6
| | - François Belzile
- Dép. de Phytologie and Institut de Biologie Intégrative et des Systèmes, Univ. Laval, Quebec City, QC, Canada, G1V 0A6
| | - Louise S O'Donoughue
- CÉROM, Centre de recherche sur les grains Inc., 740 chemin Trudeau, Saint-Mathieu-de-Beloeil, Canada, QC, J3G 0E2
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26
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Wang H, Zhu S, Dang X, Liu E, Hu X, Eltahawy MS, Zaid IU, Hong D. Favorable alleles mining for gelatinization temperature, gel consistency and amylose content in Oryza sativa by association mapping. BMC Genet 2019; 20:34. [PMID: 30890139 PMCID: PMC6423859 DOI: 10.1186/s12863-019-0735-y] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2018] [Accepted: 03/01/2019] [Indexed: 11/22/2022] Open
Abstract
Background Improving the gelatinization temperature (GT), gel consistency (GC) and amylose content (AC) for parental grain eating and cooking qualities (ECQs) are key factors for enhancing average grain ECQs for hybrid japonica rice. Results In this study, a genome-wide association mapping (GWAS) for ECQs was performed on a selected sample of 462 rice accessions in 5 environments using 262 simple sequence repeat markers. We identified 10 loci and 27 favorable alleles for GT, GC and AC, and some of these loci were overlapped with starch synthesis-related genes. Four SSR loci for the GT trait were distributed on chromosomes 3, 5, 8, and 9, of which two SSR loci were novel. Two SSR loci associated with the GC trait were distributed on chromosomes 3 and 6, although only one SSR locus was novel. Four SSR loci associated with the AC trait were distributed on chromosomes 3, 6, 10, and 11, of which three SSR loci were novel. The novel loci RM6712 and RM6327 were simultaneously identified in more than 2 environments and were potentially reliable QTLs for ECQs, with 15 parental combinations being predicted. These QTLs and parental combinations should be used in molecular breeding to improve japonica rice average ECQs. Conclusions Among the 10 SSR loci associated with GT, GC and AC for grain ECQs detected in 27 favorable alleles, the favorable allele RM3600-90bp on chromosome 9 could significantly reduce GT, RM5753-115bp on chromosome 6 could significantly increase GC, and RM6327-230bp on chromosome 11 could significantly reduce AC in hybrid japonica rice mixed rice samples. Electronic supplementary material The online version of this article (10.1186/s12863-019-0735-y) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Hui Wang
- Nanjing Agricultural University, Nanjing, 210095, China.,State Key Laboratory of Crop Genetics and Germplasm Enhancement, Nanjing Agricultural University, Nanjing, 210095, China
| | - Shangshang Zhu
- Nanjing Agricultural University, Nanjing, 210095, China.,State Key Laboratory of Crop Genetics and Germplasm Enhancement, Nanjing Agricultural University, Nanjing, 210095, China
| | - Xiaojing Dang
- Nanjing Agricultural University, Nanjing, 210095, China.,State Key Laboratory of Crop Genetics and Germplasm Enhancement, Nanjing Agricultural University, Nanjing, 210095, China
| | - Erbao Liu
- Nanjing Agricultural University, Nanjing, 210095, China.,State Key Laboratory of Crop Genetics and Germplasm Enhancement, Nanjing Agricultural University, Nanjing, 210095, China
| | - Xiaoxiao Hu
- Nanjing Agricultural University, Nanjing, 210095, China.,State Key Laboratory of Crop Genetics and Germplasm Enhancement, Nanjing Agricultural University, Nanjing, 210095, China
| | - Moaz Salah Eltahawy
- Nanjing Agricultural University, Nanjing, 210095, China.,State Key Laboratory of Crop Genetics and Germplasm Enhancement, Nanjing Agricultural University, Nanjing, 210095, China
| | - Imdad Ullah Zaid
- Nanjing Agricultural University, Nanjing, 210095, China.,State Key Laboratory of Crop Genetics and Germplasm Enhancement, Nanjing Agricultural University, Nanjing, 210095, China
| | - Delin Hong
- Nanjing Agricultural University, Nanjing, 210095, China. .,State Key Laboratory of Crop Genetics and Germplasm Enhancement, Nanjing Agricultural University, Nanjing, 210095, China.
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27
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Mérida-García R, Liu G, He S, Gonzalez-Dugo V, Dorado G, Gálvez S, Solís I, Zarco-Tejada PJ, Reif JC, Hernandez P. Genetic dissection of agronomic and quality traits based on association mapping and genomic selection approaches in durum wheat grown in Southern Spain. PLoS One 2019; 14:e0211718. [PMID: 30811415 PMCID: PMC6392243 DOI: 10.1371/journal.pone.0211718] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2018] [Accepted: 01/19/2019] [Indexed: 01/12/2023] Open
Abstract
Climatic conditions affect the growth, development and final crop production. As wheat is of paramount importance as a staple crop in the human diet, there is a growing need to study its abiotic stress adaptation through the performance of key breeding traits. New and complementary approaches, such as genome-wide association studies (GWAS) and genomic selection (GS), are used for the dissection of different agronomic traits. The present study focused on the dissection of agronomic and quality traits of interest (initial agronomic score, yield, gluten index, sedimentation index, specific weight, whole grain protein and yellow colour) assessed in a panel of 179 durum wheat lines (Triticum durum Desf.), grown under rainfed conditions in different Mediterranean environments in Southern Spain (Andalusia). The findings show a total of 37 marker-trait associations (MTAs) which affect phenotype expression for three quality traits (specific weight, gluten and sedimentation indexes). MTAs could be mapped on the A and B durum wheat subgenomes (on chromosomes 1A, 1B, 2A, 2B and 3A) through the recently available bread wheat reference assembly (IWGSC RefSeqv1). Two of the MTAs found for quality traits (gluten index and SDS) corresponded to the known Glu-B1 and Glu-A1 loci, for which candidate genes corresponding to high molecular weight glutenin subunits could be located. The GS prediction ability values obtained from the breeding materials analyzed showed promising results for traits as grain protein content, sedimentation and gluten indexes, which can be used in plant breeding programs.
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Affiliation(s)
- Rosa Mérida-García
- Instituto de Agricultura Sostenible (IAS) Consejo Superior de Investigaciones Científicas (CSIC), Alameda del Obispo s/n, Córdoba, Spain
| | - Guozheng Liu
- Department of Breeding Research, Leibniz Institute of Plant Genetics and Crop Plant Research (IPK) Gatersleben, Corrensstraße 3, Stadt Seeland, Germany
| | - Sang He
- Department of Breeding Research, Leibniz Institute of Plant Genetics and Crop Plant Research (IPK) Gatersleben, Corrensstraße 3, Stadt Seeland, Germany
| | - Victoria Gonzalez-Dugo
- Instituto de Agricultura Sostenible (IAS) Consejo Superior de Investigaciones Científicas (CSIC), Alameda del Obispo s/n, Córdoba, Spain
| | - Gabriel Dorado
- Departamento de Bioquímica y Biología Molecular, Campus Rabanales C6-1-E17, Campus de Excelencia Internacional Agroalimentario (ceiA3), Universidad de Córdoba, Córdoba, Spain
| | - Sergio Gálvez
- Universidad de Málaga, Andalucía Tech, ETSI Informática, Campus de Teatinos s/n, Málaga, Spain
| | - Ignacio Solís
- ETSIA (University of Seville), Ctra de Utrera km1, Seville, Spain
| | - Pablo J. Zarco-Tejada
- Instituto de Agricultura Sostenible (IAS) Consejo Superior de Investigaciones Científicas (CSIC), Alameda del Obispo s/n, Córdoba, Spain
| | - Jochen C. Reif
- Department of Breeding Research, Leibniz Institute of Plant Genetics and Crop Plant Research (IPK) Gatersleben, Corrensstraße 3, Stadt Seeland, Germany
| | - Pilar Hernandez
- Instituto de Agricultura Sostenible (IAS) Consejo Superior de Investigaciones Científicas (CSIC), Alameda del Obispo s/n, Córdoba, Spain
- * E-mail:
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28
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Dimou NL, Pantavou KG, Braliou GG, Bagos PG. Multivariate Methods for Meta-Analysis of Genetic Association Studies. Methods Mol Biol 2019; 1793:157-182. [PMID: 29876897 DOI: 10.1007/978-1-4939-7868-7_11] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
Multivariate meta-analysis of genetic association studies and genome-wide association studies has received a remarkable attention as it improves the precision of the analysis. Here, we review, summarize and present in a unified framework methods for multivariate meta-analysis of genetic association studies and genome-wide association studies. Starting with the statistical methods used for robust analysis and genetic model selection, we present in brief univariate methods for meta-analysis and we then scrutinize multivariate methodologies. Multivariate models of meta-analysis for a single gene-disease association studies, including models for haplotype association studies, multiple linked polymorphisms and multiple outcomes are discussed. The popular Mendelian randomization approach and special cases of meta-analysis addressing issues such as the assumption of the mode of inheritance, deviation from Hardy-Weinberg Equilibrium and gene-environment interactions are also presented. All available methods are enriched with practical applications and methodologies that could be developed in the future are discussed. Links for all available software implementing multivariate meta-analysis methods are also provided.
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Affiliation(s)
- Niki L Dimou
- Department of Computer Science and Biomedical Informatics, University of Thessaly, Lamia, Greece.,Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece
| | - Katerina G Pantavou
- Department of Computer Science and Biomedical Informatics, University of Thessaly, Lamia, Greece
| | - Georgia G Braliou
- Department of Computer Science and Biomedical Informatics, University of Thessaly, Lamia, Greece
| | - Pantelis G Bagos
- Department of Computer Science and Biomedical Informatics, University of Thessaly, Lamia, Greece.
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29
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Takenaka S, Nitta M, Nasuda S. Population structure and association analyses of the core collection of hexaploid accessions conserved ex situ in the Japanese gene bank NBRP-Wheat. Genes Genet Syst 2018; 93:237-254. [PMID: 30555105 DOI: 10.1266/ggs.18-00041] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
In this study, we investigated the genetic diversity and population structure of the core collection of hexaploid wheat accessions in the Japanese wheat gene bank NBRP-Wheat. The core collection, consisting of 188 accessions of Triticum aestivum, T. spelta, T. compactum, T. sphaerococcum, T. macha and T. vavilovii, was intensively genotyped by DArTseq markers and consisted of 20,186 SNPs and 60,077 present and absent variations (PAVs). Polymorphic markers were distributed in all chromosomes, with a tendency for smaller numbers on the D-genome chromosomes. We examined the population structure by Bayesian clustering and principal component analysis with a general linear model. Overall, the core collection was divided into seven clusters. Non-admixture accessions in each cluster indicated that the clusters reflect the geographic distribution of the accessions. Both structure analyses strongly suggested that the cluster consisting of T. spelta and T. macha is out-grouped from other hexaploid wheat accessions. We performed genome-wide association analysis pilot studies for nine quantitative and seven qualitative traits and found marker-trait associations for all traits but one, indicating that the current core collection will be useful for detecting uncharacterized QTLs associated with phenotypes of interest.
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Affiliation(s)
- Shotaro Takenaka
- Laboratory of Plant Genetics, Graduate School of Agriculture, Kyoto University.,Department of Plant Life Science, Faculty of Agriculture, Ryukoku University
| | - Miyuki Nitta
- Laboratory of Plant Genetics, Graduate School of Agriculture, Kyoto University
| | - Shuhei Nasuda
- Laboratory of Plant Genetics, Graduate School of Agriculture, Kyoto University
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30
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Rossi UA, Hasenauer FC, Caffaro ME, Raschia MA, Maurizio E, Cortez HS, Neumann RD, Poli MA, Rossetti CA. Association of an IRF3 putative functional uORF variant with resistance to Brucella infection: A candidate gene based analysis of InDel polymorphisms in goats. Cytokine 2018; 115:109-115. [PMID: 30477986 DOI: 10.1016/j.cyto.2018.11.024] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2018] [Revised: 11/06/2018] [Accepted: 11/19/2018] [Indexed: 12/22/2022]
Abstract
Brucellosis is an important zoonotic disease caused by infection with Brucella spp. It generates major economic losses in livestock production worldwide. Goats are the principal hosts of B. melitensis, the main infection agent of caprine and human brucellosis. The selection of resistance-related genes is considered one of the best long-term means to improve control to bacterial infection in domestic ruminants. We performed a candidate gene association study to test if six short insertion/deletion polymorphisms (InDels) at bacterial-infection related genes influence the resistance to Brucella infection in female creole goats. InDels (IRF3-540: rs660531540, FKBP5-294: rs448529294, TIRAP-561: rs657494561, PTPRT-588: rs667380588, KALRN-989: rs667660989 and RAB5a-016: rs661537016) were resolved by PCR-capillary electrophoresis in samples from 64 cases and 64 controls for brucellosis. Allelic frequencies were significantly different between cases and controls at IRF3-540 and KALRN-989 (p = 0.001 and 0.005). Indeed, the minor alleles (a and k) at InDels IRF3-540 and KALRN-989 were more frequent among controls than cases, providing evidence that these alleles confer protection against Brucella infection. Moreover, IRF3-540 a-containing genotypes (Aa and aa) were associated with absence of Brucella-specific antibodies in goats (p = 0.003; OR = 3.52; 95% CI = 1.55-7.96), and more specifically, a-allele was associated with resistance to Brucella infection in a dose-dependent manner. Also, we observed that the IRF3-540 deletion (a-allele) extends a conserved upstream ORF by 75 nucleotides to the main ORF, and thus it may decrease gene expression by reducing translation efficiency from the main ORF. These results suggest a potential functional role of IRF3-540 deletion in genetic resistance to Brucella infection in goats.
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Affiliation(s)
- Ursula A Rossi
- Instituto Nacional de Tecnología Agropecuaria, CICVyA, Instituto de Patobiología, Nicolás Repetto y de Los Reseros s/n, Hurlingham, Buenos Aires B1686, Argentina
| | - Flavia C Hasenauer
- Instituto Nacional de Tecnología Agropecuaria, CICVyA, Instituto de Patobiología, Nicolás Repetto y de Los Reseros s/n, Hurlingham, Buenos Aires B1686, Argentina; CONICET, Buenos Aires, Argentina
| | - María E Caffaro
- Inst. de Genética ''Ewald A. Favret'', Nicolás Repetto y de Los Reseros s/n, Hurlingham, Buenos Aires B1686, Argentina
| | - Maria A Raschia
- Inst. de Genética ''Ewald A. Favret'', Nicolás Repetto y de Los Reseros s/n, Hurlingham, Buenos Aires B1686, Argentina
| | - Estefania Maurizio
- Instituto Nacional de Tecnología Agropecuaria, CICVyA, Instituto de Patobiología, Nicolás Repetto y de Los Reseros s/n, Hurlingham, Buenos Aires B1686, Argentina
| | - Hector S Cortez
- Instituto Nacional de Tecnología Agropecuaria, IIACS, Area de Salud Animal, RN 68 (km 172) Cerrillos, Salta, Argentina
| | - Roberto D Neumann
- Instituto Nacional de Tecnología Agropecuaria, IIACS, Area de Salud Animal, RN 68 (km 172) Cerrillos, Salta, Argentina
| | - Mario A Poli
- Inst. de Genética ''Ewald A. Favret'', Nicolás Repetto y de Los Reseros s/n, Hurlingham, Buenos Aires B1686, Argentina
| | - Carlos A Rossetti
- Instituto Nacional de Tecnología Agropecuaria, CICVyA, Instituto de Patobiología, Nicolás Repetto y de Los Reseros s/n, Hurlingham, Buenos Aires B1686, Argentina.
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Haplotype-Based Genome-Wide Prediction Models Exploit Local Epistatic Interactions Among Markers. G3-GENES GENOMES GENETICS 2018; 8:1687-1699. [PMID: 29549092 PMCID: PMC5940160 DOI: 10.1534/g3.117.300548] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
Genome-wide prediction approaches represent versatile tools for the analysis and prediction of complex traits. Mostly they rely on marker-based information, but scenarios have been reported in which models capitalizing on closely-linked markers that were combined into haplotypes outperformed marker-based models. Detailed comparisons were undertaken to reveal under which circumstances haplotype-based genome-wide prediction models are superior to marker-based models. Specifically, it was of interest to analyze whether and how haplotype-based models may take local epistatic effects between markers into account. Assuming that populations consisted of fully homozygous individuals, a marker-based model in which local epistatic effects inside haplotype blocks were exploited (LEGBLUP) was linearly transformable into a haplotype-based model (HGBLUP). This theoretical derivation formally revealed that haplotype-based genome-wide prediction models capitalize on local epistatic effects among markers. Simulation studies corroborated this finding. Due to its computational efficiency the HGBLUP model promises to be an interesting tool for studies in which ultra-high-density SNP data sets are studied. Applying the HGBLUP model to empirical data sets revealed higher prediction accuracies than for marker-based models for both traits studied using a mouse panel. In contrast, only a small subset of the traits analyzed in crop populations showed such a benefit. Cases in which higher prediction accuracies are observed for HGBLUP than for marker-based models are expected to be of immediate relevance for breeders, due to the tight linkage a beneficial haplotype will be preserved for many generations. In this respect the inheritance of local epistatic effects very much resembles the one of additive effects.
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Otani T, Noma H, Nishino J, Matsui S. Re-assessment of multiple testing strategies for more efficient genome-wide association studies. Eur J Hum Genet 2018. [PMID: 29523830 DOI: 10.1038/s41431-018-0125-3] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022] Open
Abstract
Although enormous costs have been dedicated to discovering relevant disease-related genetic variants, especially in genome-wide association studies (GWASs), only a small fraction of estimated heritability can be explained by these results. This is the so-called missing heritability problem. The conventional use of overly conservative multiple testing strategies based on controlling the familywise error rate (FWER), in particular with a genome-wide significance threshold of P <5 × 10-8, is one of the most important issues from a statistical perspective. To help resolve this problem, we performed comprehensive re-assessments of currently available strategies using recently published, extremely large-scale GWAS data sets of rheumatoid arthritis and schizophrenia (>50,000 subjects). The estimates of statistical power averaged for all disease-related genetic variants of the standard FWER-based strategy were only 0.09% for the rheumatoid arthritis data and 0.04% for the schizophrenia data. To design more efficient strategies, we also conducted an extensive comparison of multiple testing strategies by applying false discovery rate (FDR)-controlling procedures to these data sets and simulations, and found that the FDR-based procedures achieved higher power than the FWER-based strategy, even at a strict FDR level (e.g., FDR = 1%). We also discuss a useful alternative measure, namely "partial power," which is an averaged power for detecting the clinically and biologically meaningful genetic factors with the largest effects. Simulation results suggest that the FDR-based procedures can achieve sufficient partial power (>80%) for detecting these factors (odds ratios of >1.05) with 80,000 subjects, and thus this may be a useful measure for defining realistic objectives of future GWASs.
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Affiliation(s)
- Takahiro Otani
- Risk Analysis Research Center, The Institute of Statistical Mathematics, Tachikawa, Tokyo, 190-8562, Japan
| | - Hisashi Noma
- Department of Data Science, The Institute of Statistical Mathematics, Tachikawa, Tokyo, 190-8562, Japan.
| | - Jo Nishino
- Department of Biostatistics, Nagoya University Graduate School of Medicine, Nagoya, Aichi, 466-8550, Japan
| | - Shigeyuki Matsui
- Department of Biostatistics, Nagoya University Graduate School of Medicine, Nagoya, Aichi, 466-8550, Japan
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Saba Rahim M, Sharma H, Parveen A, Roy JK. Trait Mapping Approaches Through Association Analysis in Plants. ADVANCES IN BIOCHEMICAL ENGINEERING/BIOTECHNOLOGY 2018; 164:83-108. [PMID: 29511776 DOI: 10.1007/10_2017_50] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
Previously, association mapping (AM) methodology was used to unravel genetic complications in animal science by measuring the complex traits for candidate and non-candidate genes. Nowadays, this statistical approach is widely used to clarify the complexity in plant breeding program-based genome-wide breeding strategies, marker development, and diversity analysis. This chapter is particularly focused on methodologies with limitations and provides an overview of AM models and software used up to now. Association or linkage disequilibrium mapping has become a very popular method for discovering candidate and non-candidate genes and confirmation of quantitative trait loci (QTL) on various parts of the genome and in marker-assisted selection for breeding. Previously, various QTL investigations were carried out for different plants exclusively by linkage mapping. To help to understand the basics of modern molecular genetic techniques, in this chapter we summarize previous studies done on different crops. AM offers high-resolution power when there is large genotypic diversity and low linkage disequilibrium (LD) for the germplasm being investigated. The benefits of AM, compared with traditional QTL mapping, include a relatively detailed mapping resolution and a far less time-consuming approach since no mapping populations need to be generated. The advancements in genotyping and computational techniques have encouraged the use of AM. AM provides a fascinating approach for genetic investigation of QTLs, due to its resolution and the possibility to study the various genomic areas at the same time without construction of mapping populations. In this chapter we also discuss the advantages and disadvantages of AM, especially in the dicotyledonous crops Fabaceae and Solanaceae, with various genome-size reproductive strategies (clonal vs. sexual), and statistical models. The main objective of this chapter is to highlight the uses of association genetics in major and minor crop species that have trouble being analyzed for dissection of complex traits by identification of the factor responsible for controlling the effect of trait. Graphical Abstract.
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Affiliation(s)
- M Saba Rahim
- National Agri-Food Biotechnology Institute (NABI), Mohali, India
| | - Himanshu Sharma
- National Agri-Food Biotechnology Institute (NABI), Mohali, India
| | - Afsana Parveen
- National Agri-Food Biotechnology Institute (NABI), Mohali, India
| | - Joy K Roy
- National Agri-Food Biotechnology Institute (NABI), Mohali, India.
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Rispail N, Montilla-Bascón G, Sánchez-Martín J, Flores F, Howarth C, Langdon T, Rubiales D, Prats E. Multi-Environmental Trials Reveal Genetic Plasticity of Oat Agronomic Traits Associated With Climate Variable Changes. FRONTIERS IN PLANT SCIENCE 2018; 9:1358. [PMID: 30283476 PMCID: PMC6156136 DOI: 10.3389/fpls.2018.01358] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/02/2018] [Accepted: 08/28/2018] [Indexed: 05/06/2023]
Abstract
Although oat cultivation around the Mediterranean basin is steadily increasing, its yield in these regions lags far behind those of Northern Europe. This results mainly from the poor adaptation of current oat cultivars to Mediterranean environments. Local landraces may act as reservoirs of favorable traits that could contribute to increase oat resilience in this region. To aid selection of suitable agro-climate adapted genotypes we integrated genome-wide association approaches with analysis of field assessed phenotypes of genetic variants and of the weight of associated markers across different environmental variables. Association models accounting for oat population structure were applied on either arithmetic means or best linear unbiased prediction (BLUPs) to ensure robust identification of associations with the agronomic traits evaluated. The meta-analysis of the six joint environments (mega-environment) identified several markers associated with several agronomic traits and crown rust severity. Five of these associated markers were located within expressed genes. These associations were only mildly influenced by climatic variables indicating that these markers are good candidates to improve the genetic potential of oat under Mediterranean conditions. The models also highlighted several marker-trait associations, strongly affected by particular climatic variables including high rain pre- or post-heading dates and high temperatures, revealing strong potential for oat adaptation to specific agro-climatic conditions. These results will contribute to increase oat resilience for particular climatic conditions and facilitate breeding for plant adaptation to a wider range of climatic conditions in the current scenario of climate change.
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Affiliation(s)
| | | | | | - Fernando Flores
- ETSI La Rábida, University of Huelva, Palos de la Frontera, Spain
| | - Catherine Howarth
- Institute of Biological, Environmental and Rural Sciences, University of Aberystwyth, Aberystwyth, United Kingdom
| | - Tim Langdon
- Institute of Biological, Environmental and Rural Sciences, University of Aberystwyth, Aberystwyth, United Kingdom
| | - Diego Rubiales
- Institute for Sustainable Agriculture, CSIC, Córdoba, Spain
| | - Elena Prats
- Institute for Sustainable Agriculture, CSIC, Córdoba, Spain
- *Correspondence: Elena Prats,
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Muqaddasi QH, Pillen K, Plieske J, Ganal MW, Röder MS. Genetic and physical mapping of anther extrusion in elite European winter wheat. PLoS One 2017; 12:e0187744. [PMID: 29121111 PMCID: PMC5679578 DOI: 10.1371/journal.pone.0187744] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2017] [Accepted: 10/25/2017] [Indexed: 12/13/2022] Open
Abstract
The production and cultivation of hybrid wheat is a possible strategy to close the yield gap in wheat. Efficient hybrid wheat seed production largely depends on high rates of cross-pollination which can be ensured through high anther extrusion (AE) by male parental lines. Here, we report the AE capacity and elucidate its genetics in 514 elite European winter wheat varieties via genome-wide association studies (GWAS). We observed a wide range of variation among genotypes and a high heritability (0.80) for AE. The whole panel was genotyped with the 35k Affymetrix and 90k iSELECT single nucleotide polymorphism (SNP) arrays plus Ppd-D1, Rht-B1 and Rht-D1 candidate markers. GWAS revealed 51 marker-trait associations (MTAs) on chromosomes 1A, 1B, 2A, 4D and 5B, with Rht-D1 (4D) being the most significant marker. Division of whole panel according to the Rht-D1 genotype resulted in 212 and 294 varieties harboring Rht-D1a and Rht-D1b allele, respectively. The presence of Rht-D1a compared to Rht-D1b (mutant) allele had a large phenotypic influence on AE resulting in its ~17% increase. GWAS performed on the sub-panels detected novel MTAs on chromosomes 2D, 3B and 6A with increased phenotypic variance imparted by individual markers. Our study shows that AE is a highly quantitative trait and wild type Rht-D1a allele greatly improves AE. Moreover, demarcating the quantitative trait loci regions based on intra-chromosomal linkage disequilibrium revealed AE’s candidate genes/genomic regions. Understanding the genetics of AE in elite European wheat and utilizing the linked markers in breeding programs can help to enhance cross-pollination for better exploitation of heterosis.
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Affiliation(s)
- Quddoos H. Muqaddasi
- Leibniz Institute of Plant Genetics and Crop Plant Research (IPK), Stadt Seeland OT Gatersleben, Germany
- * E-mail:
| | - Klaus Pillen
- Institute of Agricultural and Nutritional Sciences, Martin-Luther-University Halle-Wittenberg, Halle, Germany
| | - Jörg Plieske
- TraitGenetics GmbH, Stadt Seeland OT Gatersleben, Germany
| | | | - Marion S. Röder
- Leibniz Institute of Plant Genetics and Crop Plant Research (IPK), Stadt Seeland OT Gatersleben, Germany
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Mahajan R, Zargar SM, Salgotra RK, Singh R, Wani AA, Nazir M, Sofi PA. Linkage disequilibrium based association mapping of micronutrients in common bean ( Phaseolus vulgaris L.): a collection of Jammu & Kashmir, India. 3 Biotech 2017; 7:295. [PMID: 28868222 DOI: 10.1007/s13205-017-0928-x] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2016] [Accepted: 08/22/2017] [Indexed: 12/15/2022] Open
Abstract
Micronutrient deficiencies are of major concern in human health and plant metabolism. Iron (Fe), zinc (Zn), iodine (I), selenium (Se) are regarded as micronutrients having major impact on human health. More than 50% of populations mainly from developing countries are suffering from one or the other micronutrient malnutrition. Ensuring adequate supply of these micronutrients through diet consisting of staple foods, such as common bean (Phaseolus vulgaris L.) is must. Here, we evaluated common bean genotypes that were collected from various regions of Jammu and Kashmir, India for Fe, Zn and protein contents and used SSRs to identify the markers associated with these traits. We found significant variation among genotypes for Fe, Zn and protein contents. Genotype R2 was having 7.22 mg 100 g-1 of Fe content, genotype K15 with 1.93 mg 100 g-1 of Zn content and genotype KS6 with 31.6% of protein content. Diversity study was done using both cluster and structure based approach. Further, association mapping analysis using General Linear Method (GLM) approach was done to identify SSRs associated with accumulation of Fe, Zn and protein. 13 SSRs were identified that significantly (p < 0.05) showed association with Fe, Zn and protein contents in common bean. The markers associated with Fe were located on chromosome no. 2, 5, 6, 7, 9 and 10, markers associated with Zn were located on chromosome no. 1, 3, 5, 7 and 10 whereas only one marker located on chromosome no. 4 was found associated with protein content. These findings will provide potential opportunity to improve Fe and Zn concentrations in common bean, through molecular breeding.
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Affiliation(s)
- Reetika Mahajan
- School of Biotechnology, Sher-e-Kashmir University of Agricultural Science and Technology of Jammu, Chatha, Jammu, Jammu & Kashmir India
| | - Sajad Majeed Zargar
- Division of Plant Biotechnology, Sher-e-Kashmir University of Agricultural Science and Technology of Kashmir, Shalimar, Srinagar, Jammu & Kashmir India
| | - R K Salgotra
- School of Biotechnology, Sher-e-Kashmir University of Agricultural Science and Technology of Jammu, Chatha, Jammu, Jammu & Kashmir India
| | - Ravinder Singh
- School of Biotechnology, Sher-e-Kashmir University of Agricultural Science and Technology of Jammu, Chatha, Jammu, Jammu & Kashmir India
| | - Aijaz Ahmad Wani
- Department of Botany, University of Kashmir, Hazratbal, Srinagar, Jammu & Kashmir India
| | - Muslima Nazir
- Division of Plant Biotechnology, Sher-e-Kashmir University of Agricultural Science and Technology of Kashmir, Shalimar, Srinagar, Jammu & Kashmir India
| | - Parvaze A Sofi
- Division of Plant Breeding and Genetics, Sher-e-Kashmir University of Agricultural Science and Technology of Kashmir, Shalimar, Srinagar, Jammu & Kashmir India
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The importance of gene-environment interactions in human obesity. Clin Sci (Lond) 2017; 130:1571-97. [PMID: 27503943 DOI: 10.1042/cs20160221] [Citation(s) in RCA: 120] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2016] [Accepted: 05/23/2016] [Indexed: 12/16/2022]
Abstract
The worldwide obesity epidemic has been mainly attributed to lifestyle changes. However, who becomes obese in an obesity-prone environment is largely determined by genetic factors. In the last 20 years, important progress has been made in the elucidation of the genetic architecture of obesity. In parallel with successful gene identifications, the number of gene-environment interaction (GEI) studies has grown rapidly. This paper reviews the growing body of evidence supporting gene-environment interactions in the field of obesity. Heritability, monogenic and polygenic obesity studies provide converging evidence that obesity-predisposing genes interact with a variety of environmental, lifestyle and treatment exposures. However, some skepticism remains regarding the validity of these studies based on several issues, which include statistical modelling, confounding, low replication rate, underpowered analyses, biological assumptions and measurement precision. What follows in this review includes (1) an introduction to the study of GEI, (2) the evidence of GEI in the field of obesity, (3) an outline of the biological mechanisms that may explain these interaction effects, (4) methodological challenges associated with GEI studies and potential solutions, and (5) future directions of GEI research. Thus far, this growing body of evidence has provided a deeper understanding of GEI influencing obesity and may have tremendous applications in the emerging field of personalized medicine and individualized lifestyle recommendations.
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Hess M, Druet T, Hess A, Garrick D. Fixed-length haplotypes can improve genomic prediction accuracy in an admixed dairy cattle population. Genet Sel Evol 2017; 49:54. [PMID: 28673233 PMCID: PMC5494768 DOI: 10.1186/s12711-017-0329-y] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2016] [Accepted: 06/26/2017] [Indexed: 01/05/2023] Open
Abstract
Background Fitting covariates representing the number of haplotype alleles rather than single nucleotide polymorphism (SNP) alleles may increase genomic prediction accuracy if linkage disequilibrium between quantitative trait loci and SNPs is inadequate. The objectives of this study were to evaluate the accuracy, bias and computation time of Bayesian genomic prediction methods that fit fixed-length haplotypes or SNPs. Genotypes at 37,740 SNPs that were common to Illumina BovineSNP50 and high-density panels were phased for ~58,000 New Zealand dairy cattle. Females born before 1 June 2008 were used for training, and genomic predictions for milk fat yield (n = 24,823), liveweight (n = 13,283) and somatic cell score (n = 24,864) were validated within breed (predominantly Holstein–Friesian, predominantly Jersey, or admixed KiwiCross) in later-born females. Covariates for haplotype alleles of five lengths (125, 250, 500 kb, 1 or 2 Mb) were generated and rare haplotypes were removed at four thresholds (1, 2, 5 or 10%), resulting in 20 scenarios tested. Genomic predictions fitting covariates for either SNPs or haplotypes were calculated by using BayesA, BayesB or BayesN. This is the first study to quantify the accuracy of genomic prediction using haplotypes across the whole genome in an admixed population. Results A correlation of 0.349 ± 0.016 between yield deviation and genomic breeding values was obtained for milk fat yield in Holstein–Friesians using BayesA fitting covariates. Genomic predictions were more accurate with short haplotypes than with SNPs but less accurate with longer haplotypes than with SNPs. Fitting only the most frequent haplotype alleles reduced computation time with little decrease in prediction accuracy for short haplotypes. Trends were similar for all traits and breeds and there was little difference between Bayesian methods. Conclusions Fitting covariates for haplotype alleles rather than SNPs can increase prediction accuracy, although it decreased drastically for long (>500 kb) haplotypes. In this population, fitting 250 kb haplotypes with a 1% frequency threshold resulted in the highest genomic prediction accuracy and fitting 125 kb haplotypes with a 10% frequency threshold improved genomic prediction accuracy with comparable computation time to fitting SNPs. This increased accuracy is likely to increase genetic gain by changing the ranking of selection candidates. Electronic supplementary material The online version of this article (doi:10.1186/s12711-017-0329-y) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Melanie Hess
- Iowa State University, Ames, IA, USA. .,LIC, Hamilton, New Zealand.
| | | | | | - Dorian Garrick
- Iowa State University, Ames, IA, USA.,Massey University, Palmerston North, New Zealand
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dos Santos BP, Marinho CRM, Marques TEBS, Angelo LKG, Malta MVDS, Duzzioni M, de Castro OW, Leite JP, Barbosa FT, Gitaí DLG. Genetic susceptibility in Juvenile Myoclonic Epilepsy: Systematic review of genetic association studies. PLoS One 2017; 12:e0179629. [PMID: 28636645 PMCID: PMC5479548 DOI: 10.1371/journal.pone.0179629] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2016] [Accepted: 06/01/2017] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Several genetic association investigations have been performed over the last three decades to identify variants underlying Juvenile Myoclonic Epilepsy (JME). Here, we evaluate the accumulating findings and provide an updated perspective of these studies. METHODOLOGY A systematic literature search was conducted using the PubMed, Embase, Scopus, Lilacs, epiGAD, Google Scholar and Sigle up to February 12, 2016. The quality of the included studies was assessed by a score and classified as low and high quality. Beyond outcome measures, information was extracted on the setting for each study, characteristics of population samples and polymorphisms. RESULTS Fifty studies met eligibility criteria and were used for data extraction. With a single exception, all studies used a candidate gene approach, providing data on 229 polymorphisms in or near 55 different genes. Of variants investigating in independent data sets, only rs2029461 SNP in GRM4, rs3743123 in CX36 and rs3918149 in BRD2 showed a significant association with JME in at least two different background populations. The lack of consistent associations might be due to variations in experimental design and/or limitations of the approach. CONCLUSIONS Thus, despite intense research evidence established, specific genetic variants in JME susceptibility remain inconclusive. We discussed several issues that may compromise the quality of the results, including methodological bias, endophenotype and potential involvement of epigenetic factors. PROSPERO REGISTRATION NUMBER CRD42016036063.
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Affiliation(s)
- Bruna Priscila dos Santos
- Department of Cellular and Molecular Biology, Institute of Biological Sciences and Health, Federal University of Alagoas, Maceio, Alagoas, Brazil
| | - Chiara Rachel Maciel Marinho
- Department of Cellular and Molecular Biology, Institute of Biological Sciences and Health, Federal University of Alagoas, Maceio, Alagoas, Brazil
| | | | - Layanne Kelly Gomes Angelo
- Department of Cellular and Molecular Biology, Institute of Biological Sciences and Health, Federal University of Alagoas, Maceio, Alagoas, Brazil
| | - Maísa Vieira da Silva Malta
- Department of Cellular and Molecular Biology, Institute of Biological Sciences and Health, Federal University of Alagoas, Maceio, Alagoas, Brazil
| | - Marcelo Duzzioni
- Department of Pharmacology, Institute of Biological Sciences and Health, Federal University of Alagoas, Maceio, Alagoas, Brazil
| | - Olagide Wagner de Castro
- Department of Physiology, Institute of Biological Sciences and Health, Federal University of Alagoas, Maceio, Alagoas, Brazil
| | - João Pereira Leite
- Division of Neurology, Department of Neurosciences and Behavioral Sciences, Ribeirão Preto School of Medicine, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
| | | | - Daniel Leite Góes Gitaí
- Department of Cellular and Molecular Biology, Institute of Biological Sciences and Health, Federal University of Alagoas, Maceio, Alagoas, Brazil
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Zhou Q, Zhou C, Zheng W, Mason AS, Fan S, Wu C, Fu D, Huang Y. Genome-Wide SNP Markers Based on SLAF-Seq Uncover Breeding Traces in Rapeseed ( Brassica napus L.). FRONTIERS IN PLANT SCIENCE 2017; 8:648. [PMID: 28503182 DOI: 10.3389/fpls.2015.0648] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 02/06/2017] [Accepted: 04/10/2017] [Indexed: 05/26/2023]
Abstract
Single Nucleotide Polymorphisms (SNPs) are the most abundant and richest form of genomic polymorphism, and hence make highly favorable markers for genetic map construction and genome-wide association studies. In this study, a total of 300 rapeseed accessions (278 representative of Chinese germplasm, plus 22 outgroup accessions of different origins and ecotypes) were collected and sequenced using Specific-Locus Amplified Fragment Sequencing (SLAF-seq) technology, obtaining 660.25M reads with an average sequencing depth of 6.27 × and a mean Q30 of 85.96%. Based on the 238,711 polymorphic SLAF tags a total of 1,197,282 SNPs were discovered, and a subset of 201,817 SNPs with minor allele frequency >0.05 and integrity >0.8 were selected. Of these, 30,877 were designated SNP "hotspots," and 41 SNP-rich genomic regions could be delineated, with 100 genes associated with plant resistance, vernalization response, and signal transduction detected in these regions. Subsequent analysis of genetic diversity, linkage disequilibrium (LD), and population structure in the 300 accessions was carried out based on the 201,817 SNPs. Nine subpopulations were observed based on the population structure analysis. Hierarchical clustering and principal component analysis divided the 300 varieties roughly in accordance with their ecotype origins. However, spring-type varieties were intermingled with semi-winter type varieties, indicating frequent hybridization between spring and semi-winter ecotypes in China. In addition, LD decay across the whole genome averaged 299 kb when r2 = 0.1, but the LD decay in the A genome (43 kb) was much shorter than in the C genome (1,455 kb), supporting the targeted introgression of the A genome from progenitor species B. rapa into Chinese rapeseed. This study also lays the foundation for genetic analysis of important agronomic traits using this rapeseed population.
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Affiliation(s)
- Qinghong Zhou
- Key Laboratory of Crop Physiology, Ecology and Genetic Breeding, Ministry of Education, Agronomy College, Jiangxi Agricultural UniversityNanchang, China
| | - Can Zhou
- Key Laboratory of Crop Physiology, Ecology and Genetic Breeding, Ministry of Education, Agronomy College, Jiangxi Agricultural UniversityNanchang, China
| | - Wei Zheng
- Jiangxi Institute of Red SoilJinxian, China
| | - Annaliese S Mason
- Plant Breeding Department, iFZ Research Centre for Biosystems, Land Use and Nutrition, Justus Liebig UniversityGiessen, Germany
| | - Shuying Fan
- Key Laboratory of Crop Physiology, Ecology and Genetic Breeding, Ministry of Education, Agronomy College, Jiangxi Agricultural UniversityNanchang, China
| | - Caijun Wu
- Key Laboratory of Crop Physiology, Ecology and Genetic Breeding, Ministry of Education, Agronomy College, Jiangxi Agricultural UniversityNanchang, China
| | - Donghui Fu
- Key Laboratory of Crop Physiology, Ecology and Genetic Breeding, Ministry of Education, Agronomy College, Jiangxi Agricultural UniversityNanchang, China
| | - Yingjin Huang
- Key Laboratory of Crop Physiology, Ecology and Genetic Breeding, Ministry of Education, Agronomy College, Jiangxi Agricultural UniversityNanchang, China
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Abstract
Background Alcoholism has a strong genetic component. Twin studies have demonstrated the heritability of a large proportion of phenotypic variance of alcoholism ranging from 50–80%. The search for genetic variants associated with this complex behavior has epitomized sequence-based studies for nearly a decade. The limited success of genome-wide association studies (GWAS), possibly precipitated by the polygenic nature of complex traits and behaviors, however, has demonstrated the need for novel, multivariate models capable of quantitatively capturing interactions between a host of genetic variants and their association with non-genetic factors. In this regard, capturing the network of SNP by SNP or SNP by environment interactions has recently gained much interest. Results Here, we assessed 3,776 individuals to construct a network capable of detecting and quantifying the interactions within and between plausible genetic and environmental factors of alcoholism. In this regard, we propose the use of first-order dependence tree of maximum weight as a potential statistical learning technique to delineate the pattern of dependencies underpinning such a complex trait. Using a predictive based analysis, we further rank the genes, demographic factors, biological pathways, and the interactions represented by our SNP \documentclass[12pt]{minimal}
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\begin{document}$$ \times $$\end{document}×E network. The proposed framework is quite general and can be potentially applied to the study of other complex traits. Electronic supplementary material The online version of this article (doi:10.1186/s12918-017-0403-7) contains supplementary material, which is available to authorized users.
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Zhou Q, Zhou C, Zheng W, Mason AS, Fan S, Wu C, Fu D, Huang Y. Genome-Wide SNP Markers Based on SLAF-Seq Uncover Breeding Traces in Rapeseed ( Brassica napus L.). FRONTIERS IN PLANT SCIENCE 2017; 8:648. [PMID: 28503182 PMCID: PMC5409215 DOI: 10.3389/fpls.2017.00648] [Citation(s) in RCA: 44] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/06/2017] [Accepted: 04/10/2017] [Indexed: 05/18/2023]
Abstract
Single Nucleotide Polymorphisms (SNPs) are the most abundant and richest form of genomic polymorphism, and hence make highly favorable markers for genetic map construction and genome-wide association studies. In this study, a total of 300 rapeseed accessions (278 representative of Chinese germplasm, plus 22 outgroup accessions of different origins and ecotypes) were collected and sequenced using Specific-Locus Amplified Fragment Sequencing (SLAF-seq) technology, obtaining 660.25M reads with an average sequencing depth of 6.27 × and a mean Q30 of 85.96%. Based on the 238,711 polymorphic SLAF tags a total of 1,197,282 SNPs were discovered, and a subset of 201,817 SNPs with minor allele frequency >0.05 and integrity >0.8 were selected. Of these, 30,877 were designated SNP "hotspots," and 41 SNP-rich genomic regions could be delineated, with 100 genes associated with plant resistance, vernalization response, and signal transduction detected in these regions. Subsequent analysis of genetic diversity, linkage disequilibrium (LD), and population structure in the 300 accessions was carried out based on the 201,817 SNPs. Nine subpopulations were observed based on the population structure analysis. Hierarchical clustering and principal component analysis divided the 300 varieties roughly in accordance with their ecotype origins. However, spring-type varieties were intermingled with semi-winter type varieties, indicating frequent hybridization between spring and semi-winter ecotypes in China. In addition, LD decay across the whole genome averaged 299 kb when r2 = 0.1, but the LD decay in the A genome (43 kb) was much shorter than in the C genome (1,455 kb), supporting the targeted introgression of the A genome from progenitor species B. rapa into Chinese rapeseed. This study also lays the foundation for genetic analysis of important agronomic traits using this rapeseed population.
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Affiliation(s)
- Qinghong Zhou
- Key Laboratory of Crop Physiology, Ecology and Genetic Breeding, Ministry of Education, Agronomy College, Jiangxi Agricultural UniversityNanchang, China
| | - Can Zhou
- Key Laboratory of Crop Physiology, Ecology and Genetic Breeding, Ministry of Education, Agronomy College, Jiangxi Agricultural UniversityNanchang, China
| | - Wei Zheng
- Jiangxi Institute of Red SoilJinxian, China
| | - Annaliese S. Mason
- Plant Breeding Department, iFZ Research Centre for Biosystems, Land Use and Nutrition, Justus Liebig UniversityGiessen, Germany
| | - Shuying Fan
- Key Laboratory of Crop Physiology, Ecology and Genetic Breeding, Ministry of Education, Agronomy College, Jiangxi Agricultural UniversityNanchang, China
| | - Caijun Wu
- Key Laboratory of Crop Physiology, Ecology and Genetic Breeding, Ministry of Education, Agronomy College, Jiangxi Agricultural UniversityNanchang, China
| | - Donghui Fu
- Key Laboratory of Crop Physiology, Ecology and Genetic Breeding, Ministry of Education, Agronomy College, Jiangxi Agricultural UniversityNanchang, China
- *Correspondence: Donghui Fu
| | - Yingjin Huang
- Key Laboratory of Crop Physiology, Ecology and Genetic Breeding, Ministry of Education, Agronomy College, Jiangxi Agricultural UniversityNanchang, China
- Yingjin Huang
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43
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Aoun M, Breiland M, Kathryn Turner M, Loladze A, Chao S, Xu SS, Ammar K, Anderson JA, Kolmer JA, Acevedo M. Genome-Wide Association Mapping of Leaf Rust Response in a Durum Wheat Worldwide Germplasm Collection. THE PLANT GENOME 2016; 9. [PMID: 27902791 DOI: 10.3835/plantgenome2016.01.0008] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/21/2023]
Abstract
Leaf rust (caused by Erikss. []) is increasingly impacting durum wheat ( L. var. ) production with the recent appearance of races with virulence to widely grown cultivars in many durum producing areas worldwide. A highly virulent race on durum wheat was recently detected in Kansas. This race may spread to the northern Great Plains, where most of the US durum wheat is produced. The objective of this study was to identify sources of resistance to several races from the United States and Mexico at seedling stage in the greenhouse and at adult stage in field experiments. Genome-wide association study (GWAS) was used to identify single-nucleotide polymorphism (SNP) markers associated with leaf rust response in a worldwide durum wheat collection of 496 accessions. Thirteen accessions were resistant across all experiments. Association mapping revealed 88 significant SNPs associated with leaf rust response. Of these, 33 SNPs were located on chromosomes 2A and 2B, and 55 SNPs were distributed across all other chromosomes except for 1B and 7B. Twenty markers were associated with leaf rust response at seedling stage, while 68 markers were associated with leaf rust response at adult plant stage. The current study identified a total of 14 previously uncharacterized loci associated with leaf rust response in durum wheat. The discovery of these loci through association mapping (AM) is a significant step in identifying useful sources of resistance that can be used to broaden the relatively narrow leaf rust resistance spectrum in durum wheat germplasm.
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Ye C, Hu Z, Wu E, Yang X, Buford UJ, Guo Z, Saveanu RV. Two SNAP-25 genetic variants in the binding site of multiple microRNAs and susceptibility of ADHD: A meta-analysis. J Psychiatr Res 2016; 81:56-62. [PMID: 27380186 DOI: 10.1016/j.jpsychires.2016.06.007] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2016] [Revised: 05/23/2016] [Accepted: 06/10/2016] [Indexed: 12/14/2022]
Abstract
The aim of this meta-analysis is to assess the associations between two most widely investigated polymorphisms (rs3746544 and rs1051312) in the 3'UTR of the SNAP-25 gene and susceptibility of ADHD. Two investigators selected related studies and assessed methodological quality independently. Six studies were included in this meta-analysis for a total of 715 cases and 655 controls. There is no apparent association between rs3746544 polymorphisms and risk of ADHD. However, subgroup analysis based on ethnicity demonstrated a strong association between rs3746544 polymorphism and ADHD in the subset of Asian participants, but not among Caucasians. Compared to the T allele, the allele G was associated with a significantly decreased risk of developing ADHD in the Asian population (odds ratio (OR) = 0.70, 95% confidence interval (CI) = 0.52-0.95, p = 0.02). The association between the TT genotype and ADHD risk was also significantly increased as compared to G/T (OR = 1.56, 95% CI = 1.00-2.44, p = 0.05) and the dominant genetic model (GG + GT vs. TT: OR = 1.51, 95% CI = 1.07-2.13, p = 0.02). For the rs1051312 SNP, being homozygous for the minor allele (C/C) was associated with a 3.66 higher odds of ADHD as compared to cases homozygous for the major allele (T/T) (95% CI = 1.64-8.13, p = 0.001), and 3.57 higher odds as compared to heterozygous (C/T) carriers (95% CI = 2.01-12.90, p < 0.001). Our results suggest that the polymorphisms rs3746544 and rs1051312 may increase the odds of developing ADHD. Additional studies are needed to confirm these findings.
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Affiliation(s)
- Chuanzhong Ye
- Department of Psychiatry & Behavioral Sciences, University of Miami Miller School of Medicine/Jackson Health System, 1695 NW 9th Ave, 33136, United States.
| | - Zhijian Hu
- Department of Epidemiology and Health Statistics, Fujian Medical University, 1 Xue Yuan Road University Town, Fujian, 350108, China
| | - Evan Wu
- Department of Health Sciences, University of Miami Miller School of Medicine, 1120 NW 14th St, Miami, FL, 33136, United States
| | - Xiaolu Yang
- Department of Epidemiology and Health Statistics, Fujian Medical University, 1 Xue Yuan Road University Town, Fujian, 350108, China
| | - Ushimbra J Buford
- Department of Psychiatry & Behavioral Sciences, University of Miami Miller School of Medicine/Jackson Health System, 1695 NW 9th Ave, 33136, United States
| | - Zhihong Guo
- Department of Psychiatry & Behavioral Sciences, University of Miami Miller School of Medicine/Jackson Health System, 1695 NW 9th Ave, 33136, United States
| | - Radu V Saveanu
- Department of Psychiatry & Behavioral Sciences, University of Miami Miller School of Medicine/Jackson Health System, 1695 NW 9th Ave, 33136, United States
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Van der Auwera S, Teumer A, Hertel J, Homuth G, Völker U, Lucht MJ, Degenhardt F, Schulze T, Rietschel M, Nöthen MM, John U, Nauck M, Grabe HJ. The inverse link between genetic risk for schizophrenia and migraine through NMDA (N-methyl-D-aspartate) receptor activation via D-serine. Eur Neuropsychopharmacol 2016; 26:1507-1515. [PMID: 27394076 DOI: 10.1016/j.euroneuro.2016.03.019] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2015] [Revised: 02/18/2016] [Accepted: 03/24/2016] [Indexed: 10/21/2022]
Abstract
Schizophrenia has a considerable genetic background. Epidemiological studies suggest an inverse clinical association between schizophrenia and migraine. However, it is unclear to what extent this inverse comorbidity can be explained by genetic mechanisms or by schizophrenia-related behavioral factors. For both disorders hypotheses of glutamate N-methyl-D-aspartate (NMDA) receptor dysfunction have been developed in the past. We hypothesized that both conditions share common genetic factors with inverse effects, primary in the glutamatergic system and genes involved in NMDA activation. Data from the population based Study of Health in Pomerania (N=3973) were used. Based on the results from the recent genome-wide association study for schizophrenia, we calculated polygenic scores (PRS) for subsets of SNPs with different p-value cutoffs and for biological sub-entities. These scores were tested for an association of distinct biological pathways with migraine. The PRS for schizophrenia was inversely associated with migraine in our sample. This association was exclusively based on the genome-wide hits and on single nucleotide polymorphisms near or within genes encoding proteins involved in glutamatergic neurotransmission. This association could be attributed to a single intronic variant rs4523957 in SRR encoding serine-racemase. Additional expression quantitative trait loci analyses of functional variants in SRR and gene-by-gene interaction analyses further supported the validity of this finding. SRR represents the rate limiting enzyme for the synthesis of D-serine, an important co-agonist of the NMDA receptor. According to our results, a decreased versus increased activation of NMDA receptors may play a role in the etiology of schizophrenia, as well as in migraine.
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Affiliation(s)
- Sandra Van der Auwera
- Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Ellernholzstraße 1-2, 17475 Greifswald, Germany.
| | - Alexander Teumer
- Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany
| | - Johannes Hertel
- Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Ellernholzstraße 1-2, 17475 Greifswald, Germany
| | - Georg Homuth
- Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany
| | - Uwe Völker
- Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany
| | - Michael J Lucht
- Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Ellernholzstraße 1-2, 17475 Greifswald, Germany
| | - Franziska Degenhardt
- Institute of Human Genetics, University of Bonn, Bonn, Germany; Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany
| | - Thomas Schulze
- Department of Psychiatry and Psychotherapy, University Medical Center, Göttingen, Germany; Institute of Psychiatric Phenomics and Genomics (IPPG), Ludwig-Maximilians-University, Munich, Germany
| | - Marcella Rietschel
- Division of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Markus M Nöthen
- Institute of Human Genetics, University of Bonn, Bonn, Germany; Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany
| | - Ulrich John
- Institute of Social Medicine and Prevention, University Medicine Greifswald, Greifswald, Germany
| | - Matthias Nauck
- Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany
| | - Hans Jörgen Grabe
- Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Ellernholzstraße 1-2, 17475 Greifswald, Germany
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Zondervan KT, Rahmioglu N, Morris AP, Nyholt DR, Montgomery GW, Becker CM, Missmer SA. Beyond Endometriosis Genome-Wide Association Study: From Genomics to Phenomics to the Patient. Semin Reprod Med 2016; 34:242-54. [PMID: 27513026 PMCID: PMC5693320 DOI: 10.1055/s-0036-1585408] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Endometriosis is a heritable, complex chronic inflammatory disease, for which much of the causal pathogenic mechanism remains unknown. Genome-wide association studies (GWAS) to date have identified 12 single nucleotide polymorphisms at 10 independent genetic loci associated with endometriosis. Most of these were more strongly associated with revised American Fertility Society stage III/IV, rather than stage I/II. The loci are almost all located in intergenic regions that are known to play a role in the regulation of expression of target genes yet to be identified. To identify the target genes and pathways perturbed by the implicated variants, studies are required involving functional genomic annotation of the surrounding chromosomal regions, in terms of transcription factor binding, epigenetic modification (e.g., DNA methylation and histone modification) sites, as well as their correlation with RNA transcription. These studies need to be conducted in tissue types relevant to endometriosis-in particular, endometrium. In addition, to allow biologically and clinically relevant interpretation of molecular profiling data, they need to be combined and correlated with detailed, systematically collected phenotypic information (surgical and clinical). The WERF Endometriosis Phenome and Biobanking Harmonisation Project is a global standardization initiative that has produced consensus data and sample collection protocols for endometriosis research. These now pave the way for collaborative studies integrating phenomic with genomic data, to identify informative subtypes of endometriosis that will enhance understanding of the pathogenic mechanisms of the disease and discovery of novel, targeted treatments.
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Affiliation(s)
- Krina T. Zondervan
- Endometriosis CaRe Centre, Nuffield Dept of Obstetrics & Gynaecology, University of Oxford, John Radcliffe Hospital, Oxford, UK
- Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford, UK
| | - Nilufer Rahmioglu
- Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford, UK
| | - Andrew P. Morris
- Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford, UK
- Dept of Biostatistics, Department of Biostatistics, Faculty of Health & Life Sciences, University of Liverpool, 1st floor Duncan Building, Daulby Street, Liverpool, UK
| | - Dale R. Nyholt
- Institute of Health and Biomedical Innovation (IHBI), Queensland University of Technology, Brisbane, Australia
| | - Grant W. Montgomery
- QIMR Berghofer Medical Research Institute, 300 Herston Rd, Brisbane, Australia
| | - Christian M. Becker
- Endometriosis CaRe Centre, Nuffield Dept of Obstetrics & Gynaecology, University of Oxford, John Radcliffe Hospital, Oxford, UK
| | - Stacey A. Missmer
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USA
- Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USA
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Kovas Y, Plomin R. Learning Abilities and Disabilities: Generalist Genes, Specialist Environments. CURRENT DIRECTIONS IN PSYCHOLOGICAL SCIENCE 2016; 16:284-288. [PMID: 20351764 PMCID: PMC2841819 DOI: 10.1111/j.1467-8721.2007.00521.x] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
Twin studies comparing identical and fraternal twins consistently show substantial genetic influence on individual differences in learning abilities such as reading and mathematics, as well as in other cognitive abilities such as spatial ability and memory. Multivariate genetic research has shown that the same set of genes is largely responsible for genetic influence on these diverse cognitive areas. We call these "generalist genes." What differentiates these abilities is largely the environment, especially nonshared environments that make children growing up in the same family different from one another. These multivariate genetic findings of generalist genes and specialist environments have far-reaching implications for diagnosis and treatment of learning disabilities and for understanding the brain mechanisms that mediate these effects.
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Affiliation(s)
- Yulia Kovas
- Social, Genetic, and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London London, England
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Malovini A, Bellazzi R, Napolitano C, Guffanti G. Multivariate Methods for Genetic Variants Selection and Risk Prediction in Cardiovascular Diseases. Front Cardiovasc Med 2016; 3:17. [PMID: 27376073 PMCID: PMC4896915 DOI: 10.3389/fcvm.2016.00017] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2016] [Accepted: 05/23/2016] [Indexed: 01/06/2023] Open
Abstract
Over the last decade, high-throughput genotyping and sequencing technologies have contributed to major advancements in genetics research, as these technologies now facilitate affordable mapping of the entire genome for large sets of individuals. Given this, genome-wide association studies are proving to be powerful tools in identifying genetic variants that have the capacity to modify the probability of developing a disease or trait of interest. However, when the study’s goal is to evaluate the effect of the presence of genetic variants mapping to specific chromosomes regions on a specific phenotype, the candidate loci approach is still preferred. Regardless of which approach is taken, such a large data set calls for the establishment and development of appropriate analytical methods in order to translate such knowledge into biological or clinical findings. Standard univariate tests often fail to identify informative genetic variants, especially when dealing with complex traits, which are more likely to result from a combination of rare and common variants and non-genetic determinants. These limitations can partially be overcome by multivariate methods, which allow for the identification of informative combinations of genetic variants and non-genetic features. Furthermore, such methods can help to generate additive genetic scores and risk stratification algorithms that, once extensively validated in independent cohorts, could serve as useful tools to assist clinicians in decision-making. This review aims to provide readers with an overview of the main multivariate methods for genetic data analysis that could be applied to the analysis of cardiovascular traits.
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Affiliation(s)
- Alberto Malovini
- Laboratory of Informatics and Systems Engineering for Clinical Research, IRCCS Fondazione Salvatore Maugeri , Pavia , Italy
| | - Riccardo Bellazzi
- Laboratory of Informatics and Systems Engineering for Clinical Research, IRCCS Fondazione Salvatore Maugeri, Pavia, Italy; Department of Electrical, Computer and Biomedical Engineering, University of Pavia, Pavia, Italy
| | - Carlo Napolitano
- Molecular Cardiology Laboratories, IRCCS Fondazione Salvatore Maugeri , Pavia , Italy
| | - Guia Guffanti
- Department of Psychiatry, McLean Hospital, Harvard Medical School , Belmont, MA , USA
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Olsen R, Foster DJ, Upton RN, Olesen AE, Ross JR, Droney J, Sato H, Drewes AM, Kreilgaard M. Modelling the PKPD of oxycodone in experimental pain — Impact of opioid receptor polymorphisms. Eur J Pharm Sci 2016; 86:41-9. [DOI: 10.1016/j.ejps.2016.02.021] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2015] [Revised: 01/08/2016] [Accepted: 02/29/2016] [Indexed: 11/26/2022]
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50
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Sun X, Sui W, Wang X, Hou X, Ou M, Dai Y, Xiang Y. Whole-genome re-sequencing for the identification of high contribution susceptibility gene variants in patients with type 2 diabetes. Mol Med Rep 2016; 13:3735-46. [PMID: 27035118 PMCID: PMC4838165 DOI: 10.3892/mmr.2016.5014] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2015] [Accepted: 01/21/2016] [Indexed: 12/20/2022] Open
Abstract
There is increasing evidence that several genes are associated with an increased risk of type 2 diabetes (T2D); genome-wide association investigations and whole-genome re-sequencing investigations offer a useful approach for the identification of genes involved in common human diseases. To further investigate which polymorphisms confer susceptibility to T2D, the present study screened for high-contribution susceptibility gene variants Chinese patients with T2D using whole-genome re-sequencing with DNA pooling. In total, 100 Chinese individuals with T2D and 100 healthy Chinese individuals were analyzed using whole-genome re-sequencing using DNA pooling. To minimize the likelihood of systematic bias in sampling, paired-end libraries with an insert size of 500 bp were prepared for in T2D in all samples, which were then subjected to whole-genome sequencing. Each library contained four lanes. The average sequencing depth was 35.70. In the present study, 1.36 GB of clean sequence data were generated, and the resulting calculated T2D genome consensus sequence covered 99.88% of the hg19 sequence. A total of 3,974,307 single nucleotide polymorphisms were identified, of which 99.88% were in the dbSNP database. The present study also found 642,189 insertions and deletions, 5,590 structure variants (SVs), 4,713 copy number variants (CNVs) and 13,049 single nucleotide variants. A total of 1,884 somatic CNVs and 74 somatic SVs were significantly different between the cases and controls. Therefore, the present study provided validation of whole-genome re-sequencing using the DNA pooling approach. It also generated a whole-genome re-sequencing genotype database for future investigations of T2D.
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Affiliation(s)
- Xiaojuan Sun
- Department of Social Medicine and Health Service Management, College of Military Preventive Medicine, Third Military Medical University, Chongqing 400038, P.R. China
| | - Weiguo Sui
- Nephrology Department, 181st Hospital and Guangxi Key Laboratory of Metabolic Diseases Research, Guilin, Guangxi 541002, P.R. China
| | - Xiaobing Wang
- Department of Health Management Center, 181st Hospital, Guilin, Guangxi 541002, P.R. China
| | - Xianliang Hou
- Nephrology Department, 181st Hospital and Guangxi Key Laboratory of Metabolic Diseases Research, Guilin, Guangxi 541002, P.R. China
| | - Minglin Ou
- Nephrology Department, 181st Hospital and Guangxi Key Laboratory of Metabolic Diseases Research, Guilin, Guangxi 541002, P.R. China
| | - Yong Dai
- Department of Clinical Medical Research Center, The Second Clinical Medical College of Jinan University, Shenzhen People's Hospital, Shenzhen, Guangdong 518020, P.R. China
| | - Yueying Xiang
- Department of Health Management Center, 181st Hospital, Guilin, Guangxi 541002, P.R. China
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