scholarly journals Large-Scale Whole Genome Sequencing Study Reveals Genetic Architecture and Key Variants for Breast Muscle Weight in Native Chickens

Genes ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 3
Author(s):  
Xiaodong Tan ◽  
Lu Liu ◽  
Xiaojing Liu ◽  
Huanxian Cui ◽  
Ranran Liu ◽  
...  
Keyword(s):  
Genetic Architecture ◽  
Large Scale ◽  
Genome Wide Association Study ◽  
Fatty Acid Biosynthesis ◽  
Breast Muscle ◽  
Receptor Interaction ◽  
Selection Line ◽  
Economic Traits ◽  
Muscle Weight ◽  
Major Haplotype

Breast muscle weight (BrW) is one of the most important economic traits in chicken, and directional breeding for that results in both phenotypic and genetic changes. The Jingxing yellow chicken, including an original (without human-driven selection) line and a selected line (based on selection for increased intramuscular fat content), were used to dissect the genetic architecture and key variants associated with BrW. We detected 1069 high-impact single nucleotide polymorphisms (SNPs) with high conserved score and significant frequency difference between two lines. Based on the annotation result, the ECM-receptor interaction and fatty acid biosynthesis were enriched, and muscle-related genes, including MYOD1, were detected. By performing genome-wide association study for the BrW trait, we defined a major haplotype and two conserved SNPs that affected BrW. By integrated genomic and transcriptomic analysis, IGF2BP1 was identified as the crucial gene associated with BrW. In conclusion, these results offer a new insight into chicken directional selection and provide target genetic markers by which to improve chicken BrW.

scholarly journals Large-scale GWAS reveals insights into the genetic architecture of same-sex sexual behavior

Science ◽  
2019 ◽  
Vol 365 (6456) ◽  
pp. eaat7693 ◽  
Author(s):  
Andrea Ganna ◽  
Karin J. H. Verweij ◽  
Michel G. Nivard ◽  
Robert Maier ◽  
Robbee Wedow ◽  
...  
Keyword(s):  
Sexual Behavior ◽  
Genetic Architecture ◽  
Large Scale ◽  
Genome Wide Association Study ◽  
Same Sex ◽  
Genome Wide ◽  
A Genome ◽  
Number Of Sexual Partners ◽  
Opposite Sex ◽  
Males And Females

Twin and family studies have shown that same-sex sexual behavior is partly genetically influenced, but previous searches for specific genes involved have been underpowered. We performed a genome-wide association study (GWAS) on 477,522 individuals, revealing five loci significantly associated with same-sex sexual behavior. In aggregate, all tested genetic variants accounted for 8 to 25% of variation in same-sex sexual behavior, only partially overlapped between males and females, and do not allow meaningful prediction of an individual’s sexual behavior. Comparing these GWAS results with those for the proportion of same-sex to total number of sexual partners among nonheterosexuals suggests that there is no single continuum from opposite-sex to same-sex sexual behavior. Overall, our findings provide insights into the genetics underlying same-sex sexual behavior and underscore the complexity of sexuality.

scholarly journals Large-scale GWAS in sorghum reveals common genetic control of grain size among cereals

2019 ◽  
Author(s):  
Yongfu Tao ◽  
Xianrong Zhao ◽  
Xuemin Wang ◽  
Adrian Hathorn ◽  
Colleen Hunt ◽  
...  
Keyword(s):  
Grain Size ◽  
Genetic Control ◽  
Genetic Architecture ◽  
Large Scale ◽  
Molecular Mechanisms ◽  
Genome Wide Association Study ◽  
Yield Component ◽  
Cereal Crops ◽  
List Type ◽  
Genetic Potential

SummaryGrain size is a key yield component of cereal crops and a major quality attribute. It is determined by a genotype’s genetic potential and its capacity to fill the grains.This study aims to dissect the genetic architecture of grain size in sorghum via an integrated genome wide association study (GWAS) using a diversity panel of 837 individuals and a BC-NAM population of 1,421 individuals.In order to isolate genetic effects associated with grain size, rather than the genotype’s capacity to fill grain, a field treatment of removing half of the panicle during flowering was imposed. Extensive variation in grain size with high heritability was observed in both populations across 5 field trials. Subsequent GWAS analyses uncovered 92 grain size QTL, which were significantly enriched for orthologues of known grain size genes in rice and maize. Significant overlap between the 92 QTL and grain size QTL in rice and maize was also found, supporting common genetic control of this trait among cereals. Further analysis found grain size genes with opposite effect on grain number were less likely to overlap with the grain size QTL from this study, indicating the treatment facilitated identification of genetic regions related to the genetic potential of grain size rather than the capacity to fill the grain.These results enhance understanding of the genetic architecture of grain size in cereal, and pave the way for exploration of underlying molecular mechanisms in cereal crops and manipulation of this trait in breeding practices.

scholarly journals The genetic architecture of language functional connectivity

2021 ◽  
Author(s):  
Yasmina N Mekki ◽  
Vincent Guillemot ◽  
Herve Lemaitre ◽  
Amaia Carrion-Castillo ◽  
Stephanie J Forkel ◽  
...  
Keyword(s):  
Gene Expression ◽  
Functional Connectivity ◽  
Language Processing ◽  
Resting State ◽  
Genetic Architecture ◽  
Large Scale ◽  
Genome Wide Association Study ◽  
Uk Biobank ◽  
Case Control Studies ◽  
Resting State Functional Connectivity

Language is a unique trait of the human species, of which the genetic architecture remains largely unknown. Through language disorders studies, many candidate genes were identified. However, such complex and multifactorial trait is unlikely to be driven by only few genes and case-control studies, suffering from a lack of power, struggle to uncover significant variants. In parallel, neuroimaging has significantly contributed to the understanding of structural and functional aspects of language in the human brain and the recent availability of large scale cohorts like UK Biobank have made possible to study language via image-derived endophenotypes in the general population. Because of its strong relationship with task-based fMRI activations and its easiness of acquisition, resting-state functional MRI have been more popularised, making it a good surrogate of functional neuronal processes. Taking advantage of such a synergistic system by aggregating effects across spatially distributed traits, we performed a multivariate genome-wide association study (mvGWAS) between genetic variations and resting-state functional connectivity (FC) of classical brain language areas in the inferior frontal (pars opercularis, triangularis and orbitalis), temporal and inferior parietal lobes (angular and supramarginal gyri), in 32,186 participants from UK Biobank. Twenty genomic loci were found associated with language FCs, out of which three were replicated in an independent replication sample. A locus in 3p11.1, regulating EPHA3 gene expression, is found associated with FCs of the semantic component of the language network, while a locus in 15q14, regulating THBS1 gene expression is found associated with FCs of the perceptual motor language processing, bringing novel insights into the neurobiology of language.

scholarly journals Accelerated deciphering of the genetic architecture of agricultural economic traits in pigs using a low-coverage whole-genome sequencing strategy

GigaScience ◽  
2021 ◽  
Vol 10 (7) ◽  
Author(s):  
Ruifei Yang ◽  
Xiaoli Guo ◽  
Di Zhu ◽  
Cheng Tan ◽  
Cheng Bian ◽  
...  
Keyword(s):  
Genetic Architecture ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Whole Genome ◽  
Nucleotide Polymorphisms ◽  
Economic Traits ◽  
Single Nucleotide ◽  
Genome Wide ◽  
Sequencing Method ◽  
Low Coverage

Abstract Background Uncovering the genetic architecture of economic traits in pigs is important for agricultural breeding. However, high-density haplotype reference panels are unavailable in most agricultural species, limiting accurate genotype imputation in large populations. Moreover, the infinitesimal model of quantitative traits implies that weak association signals tend to be spread across most of the genome, further complicating the genetic analysis. Hence, there is a need to develop new methods for sequencing large cohorts without large reference panels. Results We describe a Tn5-based highly accurate, cost- and time-efficient, low-coverage sequencing method to obtain 11.3 million whole-genome single-nucleotide polymorphisms in 2,869 Duroc boars at a mean depth of 0.73×. On the basis of these single-nucleotide polymorphisms, a genome-wide association study was performed, resulting in 14 quantitative trait loci (QTLs) for 7 of 21 important agricultural traits in pigs. These QTLs harbour genes, such as ABCD4 for total teat number and HMGA1 for back fat thickness, and provided a starting point for further investigation. The inheritance models of the different traits varied greatly. Most follow the minor-polygene model, but this can be attributed to different reasons, such as the shaping of genetic architecture by artificial selection for this population and sufficiently interconnected minor gene regulatory networks. Conclusions Genome-wide association study results for 21 important agricultural traits identified 14 QTLs/genes and showed their genetic architectures, providing guidance for genetic improvement harnessing genomic features. The Tn5-based low-coverage sequencing method can be applied to large-scale genome studies for any species without a good reference panel and can be used for agricultural breeding.

scholarly journals Investigating the shared genetic architecture between multiple sclerosis and inflammatory bowel diseases

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yuanhao Yang ◽  
Hannah Musco ◽  
Steve Simpson-Yap ◽  
Zhihong Zhu ◽  
Ying Wang ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
Genetic Architecture ◽  
Large Scale ◽  
Genome Wide Association Study ◽  
Causal Effect ◽  
Cytotoxic T Cells ◽  
Genetic Relationships ◽  
Inflammatory Bowel ◽  
Shared Genetic

AbstractAn epidemiological association between multiple sclerosis (MS) and inflammatory bowel disease (IBD) is well established, but whether this reflects a shared genetic aetiology, and whether consistent genetic relationships exist between MS and the two predominant IBD subtypes, ulcerative colitis (UC) and Crohn’s disease (CD), remains unclear. Here, we use large-scale genome-wide association study summary data to investigate the shared genetic architecture between MS and IBD overall and UC and CD independently. We find a significantly greater genetic correlation between MS and UC than between MS and CD, and identify three SNPs shared between MS and IBD (rs13428812), UC (rs116555563) and CD (rs13428812, rs9977672) in cross-trait meta-analyses. We find suggestive evidence for a causal effect of MS on UC and IBD using Mendelian randomization, but no or weak and inconsistent evidence for a causal effect of IBD or UC on MS. We observe largely consistent patterns of tissue-specific heritability enrichment for MS and IBDs in lung, spleen, whole blood and small intestine, and identify cell-type-specific enrichment for MS and IBDs in CD4+ T cells in lung and CD8+ cytotoxic T cells in lung and spleen. Our study sheds light on the biological basis of comorbidity between MS and IBD.

How Computational Experiments Can Improve Our Understanding of the Genetic Architecture of Common Human Diseases

2020 ◽  
Vol 26 (1) ◽  
pp. 23-37 ◽  
Author(s):  
Jason H. Moore ◽  
Randal S. Olson ◽  
Peter Schmitt ◽  
Yong Chen ◽  
Elisabetta Manduchi
Keyword(s):  
Risk Factors ◽  
Genetic Risk ◽  
Genetic Architecture ◽  
Large Scale ◽  
Genome Wide Association Study ◽  
Real Data ◽  
Genetic Risk Factors ◽  
Human Diseases ◽  
Nucleotide Polymorphisms ◽  
A Genome

Susceptibility to common human diseases such as cancer is influenced by many genetic and environmental factors that work together in a complex manner. The state of the art is to perform a genome-wide association study (GWAS) that measures millions of single-nucleotide polymorphisms (SNPs) throughout the genome followed by a one-SNP-at-a-time statistical analysis to detect univariate associations. This approach has identified thousands of genetic risk factors for hundreds of diseases. However, the genetic risk factors detected have very small effect sizes and collectively explain very little of the overall heritability of the disease. Nonetheless, it is assumed that the genetic component of risk is due to many independent risk factors that contribute additively. The fact that many genetic risk factors with small effects can be detected is taken as evidence to support this notion. It is our working hypothesis that the genetic architecture of common diseases is partly driven by non-additive interactions. To test this hypothesis, we developed a heuristic simulation-based method for conducting experiments about the complexity of genetic architecture. We show that a genetic architecture driven by complex interactions is highly consistent with the magnitude and distribution of univariate effects seen in real data. We compare our results with measures of univariate and interaction effects from two large-scale GWASs of sporadic breast cancer and find evidence to support our hypothesis that is consistent with the results of our computational experiment.

scholarly journals Large-Scale Adaptive Hitchhiking Upon High Recombination inDrosophila simulans

Genetics ◽  
2003 ◽  
Vol 165 (2) ◽  
pp. 895-900 ◽  
Author(s):  
Humberto Quesada ◽  
Ursula E M Ramírez ◽  
Julio Rozas ◽  
Montserrat Aguadé
Keyword(s):  
Genetic Linkage ◽  
Large Scale ◽  
Intermediate Frequency ◽  
Core Region ◽  
Adaptive Mutation ◽  
Nucleotide Variation ◽  
Extended Haplotype ◽  
Major Haplotype ◽  
Pattern Of Variation

AbstractNatural selection is expected to leave a characteristic footprint on neighboring nucleotide variation through the effects of genetic linkage. The size of the region affected is proportional to the strength of selection and greatly reduced with the recombinational distance from the selected site. Thus, the genomic footprint of selection is generally believed to be restricted to a small DNA stretch in normal and highly recombining regions. Here, we study the effect of selection on linked polymorphism (hitchhiking effect) by surveying nucleotide variation across a highly recombining ∼88-kb genomic fragment in an African population of Drosophila simulans. We find a core region of up to 38 kb with a major haplotype at intermediate frequency. The extended haplotype structure that gradually vanishes until disappearing is unusual for a highly recombining region. Both the presence in the structured genomic domain of a single major haplotype depleted of variability and the detected spatial pattern of variation along the ∼88-kb fragment are incompatible with neutral predictions in a panmictic population. A major role of demographic effects could also be discarded. The observed pattern of variation clearly provides evidence that directional selection has acted recently on this region, sweeping out variation around a strongly adaptive mutation. Our findings suggest a major role of positive selection in shaping DNA variability even in highly recombining regions.

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