scholarly journals 026.Endometriosis — linkage, positional cloning and genome wide association

2004 ◽  
Vol 16 (9) ◽  
pp. 26
Author(s):  
G. W. Montgomery ◽  
J. Wicks ◽  
Z. Z. Zhao ◽  
D. R. Nyholt ◽  
N. G. Martin ◽  
...  
Keyword(s):  
High Throughput ◽  
Positional Cloning ◽  
Complex Disease ◽  
Association Studies ◽  
Snp Markers ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Single Experiment ◽  
Priority List ◽  
Genome Wide

Endometriosis is a complex disease which affects up to 10% of women in their reproductive years. Common symptoms include severe dysmenorrhea and pelvic pain. The disease is associated with subfertility and some malignancies. Genetic and environmental factors both influence endometriosis. The aim of our studies is to identify genetic variation contributing to endometriosis and define pathways leading to disease. We recruited a large cohort of affected sister pair (ASP) families where two sisters have had surgically confirmed disease and conducted a 10�cM genome scan. The results of the linkage analysis identified one chromosomal region with significant linkage and one region of suggestive linkage. The regions implicated by these studies are generally of the order of 20–30�cM and include several hundred genes. Locating the gene or genes contributing to disease within the region is a challenging task. The best approach to the problem is association studies using a high density of SNP markers. The recent development of human SNP maps and high throughput SNP genotyping platforms makes this task easier. We have developed high throughput SNP typing at QIMR using the Sequenom MassARRAY platform. The method allows multiple SNP assays to be genotyped on the same sample in a single experiment. Throughput and genotyping costs depend critically on this level of multiplexing and we routinely genotype 6–8 SNPs in a single assay. We are using bioinformatics and functional approaches to develop a priority list of genes to screen early in the project. SNP markers in these genes are being genotyped using the MassARRAY platform to search for genes contributing to endometriosis. In the future, genome wide association studies with our families may locate additional genes contributing to endometriosis.

scholarly journals Genome wide association analyses to understand genetic basis of flowering and plant height under three levels of nitrogen application in Brassica juncea (L.) Czern & Coss

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Javed Akhatar ◽  
Anna Goyal ◽  
Navneet Kaur ◽  
Chhaya Atri ◽  
Meenakshi Mittal ◽  
...  
Keyword(s):  
Plant Height ◽  
Indian Subcontinent ◽  
Association Studies ◽  
Snp Markers ◽  
Genome Wide Association ◽  
Strong Interactions ◽  
N Availability ◽  
Oilseed Crop ◽  
Genome Wide Association Studies ◽  
Genome Wide

AbstractTimely transition to flowering, maturity and plant height are important for agronomic adaptation and productivity of Indian mustard (B. juncea), which is a major edible oilseed crop of low input ecologies in Indian subcontinent. Breeding manipulation for these traits is difficult because of the involvement of multiple interacting genetic and environmental factors. Here, we report a genetic analysis of these traits using a population comprising 92 diverse genotypes of mustard. These genotypes were evaluated under deficient (N75), normal (N100) or excess (N125) conditions of nitrogen (N) application. Lower N availability induced early flowering and maturity in most genotypes, while high N conditions delayed both. A genotyping-by-sequencing approach helped to identify 406,888 SNP markers and undertake genome wide association studies (GWAS). 282 significant marker-trait associations (MTA's) were identified. We detected strong interactions between GWAS loci and nitrogen levels. Though some trait associated SNPs were detected repeatedly across fertility gradients, majority were identified under deficient or normal levels of N applications. Annotation of the genomic region (s) within ± 50 kb of the peak SNPs facilitated prediction of 30 candidate genes belonging to light perception, circadian, floral meristem identity, flowering regulation, gibberellic acid pathways and plant development. These included over one copy each of AGL24, AP1, FVE, FRI, GID1A and GNC. FLC and CO were predicted on chromosomes A02 and B08 respectively. CDF1, CO, FLC, AGL24, GNC and FAF2 appeared to influence the variation for plant height. Our findings may help in improving phenotypic plasticity of mustard across fertility gradients through marker-assisted breeding strategies.

scholarly journals Genome-wide association study reveals candidate genes for flowering time in cowpea (Vigna unguiculata [L.] Walp)

2021 ◽  
Author(s):  
Dev Paudel ◽  
Rocheteau Dareus ◽  
Julia Rosenwald ◽  
Maria Munoz-Amatriain ◽  
Esteban Rios
Keyword(s):  
Flowering Time ◽  
Candidate Genes ◽  
Vigna Unguiculata ◽  
Association Studies ◽  
Snp Markers ◽  
Genome Wide Association ◽  
Human Consumption ◽  
Phenotypic Variance ◽  
Genome Wide Association Studies ◽  
Genome Wide

Cowpea (Vigna unguiculata [L.] Walp., diploid, 2n = 22) is a major crop used as a protein source for human consumption as well as a quality feed for livestock. It is drought and heat tolerant and has been bred to develop varieties that are resilient to changing climates. Plant adaptation to new climates and their yield are strongly affected by flowering time. Therefore, understanding the genetic basis of flowering time is critical to advance cowpea breeding. The aim of this study was to perform genome-wide association studies (GWAS) to identify marker trait associations for flowering time in cowpea using single nucleotide polymorphism (SNP) markers. A total of 367 accessions from a cowpea mini-core collection were evaluated in Ft. Collins, CO in 2019 and 2020, and 292 accessions were evaluated in Citra, FL in 2018. These accessions were genotyped using the Cowpea iSelect Consortium Array that contained 51,128 SNPs. GWAS revealed seven reliable SNPs for flowering time that explained 8-12% of the phenotypic variance. Candidate genes including FT, GI, CRY2, LSH3, UGT87A2, LIF2, and HTA9 that are associated with flowering time were identified for the significant SNP markers. Further efforts to validate these loci will help to understand their role in flowering time in cowpea, and it could facilitate the transfer of some of this knowledge to other closely related legume species.

scholarly journals High-throughput analysis of epistasis in genome-wide association studies with BiForce

2012 ◽  
Vol 28 (15) ◽  
pp. 1957-1964 ◽  
Author(s):  
Attila Gyenesei ◽  
Jonathan Moody ◽  
Colin A.M. Semple ◽  
Chris S. Haley ◽  
Wen-Hua Wei
Keyword(s):  
High Throughput ◽  
Association Studies ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
High Throughput Analysis ◽  
Throughput Analysis ◽  
Genome Wide

scholarly journals 301 Methods of genome-wide association studies and their applications in dairy cattle

2020 ◽  
Vol 98 (Supplement_4) ◽  
pp. 31-31
Author(s):  
Li Ma
Keyword(s):  
Dairy Cattle ◽  
Complex Traits ◽  
Mixed Model ◽  
Association Studies ◽  
Snp Markers ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Genetics Research ◽  
Genome Wide ◽  
Dairy Cattle Breeding

Abstract Genome-wide association studies (GWAS) has been widely used to map quantitative trait loci (QTL) of complex traits and diseases since 2007. To date, the human GWAS catalog has accumulated 4,410 publications and 172,351 associations, and the animal QTLdb has curated 983 publications and 130,407 QTLs for cattle, largest in livestock species. During the past 13 years of development, GWAS methods has evolved from simple linear regression, using principal components to address sample relatedness, mixed models, to Bayesian full model approaches. These methods have their advantages and limitations, so it is important to choose an appropriate method, especially for studies in livestock where sample size is often limited. Note that the most popular GWAS approach, the mixed model method, originated from animal breeding and genetics research. Leveraging the national cattle genomic database at the Council on Dairy Cattle Breeding (CDCB), we have conducted GWAS analyses of various dairy traits to identify QTLs and SNP markers of importance. Combining with sequence and functional annotation data, we seek to understand the genetic basis of complex traits and to reveal useful knowledge that can be incorporated into more accurate genomic predictions in the future.

scholarly journals ALLELES ASSOCIATED TO DISEASE SEVERITY INDEX OF MAL DE RÍO CUARTO DISEASE IN MAIZE EXOTIC GERMPLASM

2020 ◽  
Vol 31 (Issue 2) ◽  
pp. 45-53
Author(s):  
E.A. Rossi ◽  
M. Ruiz ◽  
N.C. Bonamico ◽  
M.G. Balzarini
Keyword(s):  
Disease Severity ◽  
Genome Wide Association Study ◽  
Association Studies ◽  
Severity Index ◽  
Snp Markers ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Exotic Germplasm ◽  
Disease Severity Index ◽  
Genome Wide

Mal de Río Cuarto (MRC) is one of the most important viral diseases of maize in Argentina. The disease severity index (DSI) allows to combine the incidence and severity of a disease in a single metric. The genotypic reaction to MRC has been extensively studied in biparental populations. However, this complex trait has not been analyzed by genome-wide association studies (GWAS). The aim of this work is to identify new resistance alleles associated with DSI of MRC in an exotic germplasm from the International Maize and Wheat Improvement Center (CIMMYT). A population of maize lines from CIMMYT was phenotypically evaluated in environments in the area where the disease is endemic. The predictors of genetic effects (BLUP, best linear unbiased predictor) and 78,376 SNP markers (Single Nucleotide Polymorphism) were used to perform the GWAS in 186 maize lines. The values of variance components and mean-basis heritability suggest a wide genotypic variability in the population. The GWAS allowed to identify 11 putative QTL of resistance to MRC. The incorporation of exotic germplasm into local maize breeding programs could contribute favorably to the creation of hybrids with a higher level of resistance to MRC. The predictive ability of associated markers with MRC resistance indicates that marker-assisted selection is an advisable tool for selecting MRC resistant genotypes. Key words: Disease severity index; genome-wide association study; QTL; SNP

scholarly journals The druggable genome and support for target identification and validation in drug development

2016 ◽  
Author(s):  
Chris Finan ◽  
Anna Gaulton ◽  
Felix Kruger ◽  
Tom Lumbers ◽  
Tina Shah ◽  
...  
Keyword(s):  
Drug Development ◽  
Drug Target ◽  
Complex Disease ◽  
Target Identification ◽  
Association Studies ◽  
Target Selection ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
Druggable Genome

Target identification (identifying the correct drug targets for each disease) and target validation (demonstrating the effect of target perturbation on disease biomarkers and disease end-points) are essential steps in drug development. We showed previously that biomarker and disease endpoint associations of single nucleotide polymorphisms (SNPs) in a gene encoding a drug target accurately depict the effect of modifying the same target with a pharmacological agent; others have shown that genomic support for a target is associated with a higher rate of drug development success. To delineate drug development (including repurposing) opportunities arising from this paradigm, we connected complex disease- and biomarker-associated loci from genome wide association studies (GWAS) to an updated set of genes encoding druggable human proteins, to compounds with bioactivity against these targets and, where these were licensed drugs, to clinical indications. We used this set of genes to inform the design of a new genotyping array, to enable druggable genome-wide association studies for drug target selection and validation in human disease.

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