scholarly journals Fur colour in the Arctic fox: genetic architecture and consequences for fitness

2021 ◽  
Vol 288 (1959) ◽  
Author(s):  
Lukas Tietgen ◽  
Ingerid J. Hagen ◽  
Oddmund Kleven ◽  
Cecilia Di Bernardi ◽  
Thomas Kvalnes ◽  
...  
Keyword(s):  
Prey Availability ◽  
Association Studies ◽  
Major Effect ◽  
Genomic Region ◽  
The Arctic ◽  
Arctic Fox ◽  
Genome Wide Association Studies ◽  
Whole Genome ◽  
Adaptive Traits ◽  
Individual Fitness

Genome-wide association studies provide good opportunities for studying the genetic basis of adaptive traits in wild populations. Yet, previous studies often failed to identify major effect genes. In this study, we used high-density single nucleotide polymorphism and individual fitness data from a wild non-model species. Using a whole-genome approach, we identified the MC1R gene as the sole causal gene underlying Arctic fox Vulpes lagopus fur colour. Further, we showed the adaptive importance of fur colour genotypes through measures of fitness that link ecological and evolutionary processes. We found a tendency for blue foxes that are heterozygous at the fur colour locus to have higher fitness than homozygous white foxes. The effect of genotype on fitness was independent of winter duration but varied with prey availability, with the strongest effect in years of increasing rodent populations. MC1R is located in a genomic region with high gene density, and we discuss the potential for indirect selection through linkage and pleiotropy. Our study shows that whole-genome analyses can be successfully applied to wild species and identify major effect genes underlying adaptive traits. Furthermore, we show how this approach can be used to identify knowledge gaps in our understanding of interactions between ecology and evolution.

scholarly journals Family-based gene-environment interaction using sequence kernel association test (FGE-SKAT) for complex quantitative traits

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Chao-Yu Guo ◽  
Reng-Hong Wang ◽  
Hsin-Chou Yang
Keyword(s):  
Complex Traits ◽  
Association Studies ◽  
Association Test ◽  
Whole Genome Sequence ◽  
Environment Interaction ◽  
Genome Wide Association Studies ◽  
Whole Genome ◽  
Sequence Kernel Association Test ◽  
Gene Environment ◽  
Family Based

AbstractAfter the genome-wide association studies (GWAS) era, whole-genome sequencing is highly engaged in identifying the association of complex traits with rare variations. A score-based variance-component test has been proposed to identify common and rare genetic variants associated with complex traits while quickly adjusting for covariates. Such kernel score statistic allows for familial dependencies and adjusts for random confounding effects. However, the etiology of complex traits may involve the effects of genetic and environmental factors and the complex interactions between genes and the environment. Therefore, in this research, a novel method is proposed to detect gene and gene-environment interactions in a complex family-based association study with various correlated structures. We also developed an R function for the Fast Gene-Environment Sequence Kernel Association Test (FGE-SKAT), which is freely available as supplementary material for easy GWAS implementation to unveil such family-based joint effects. Simulation studies confirmed the validity of the new strategy and the superior statistical power. The FGE-SKAT was applied to the whole genome sequence data provided by Genetic Analysis Workshop 18 (GAW18) and discovered concordant and discordant regions compared to the methods without considering gene by environment interactions.

scholarly journals Fine scale human genetic structure in three regions of Cameroon reveals episodic diversifying selection

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kevin K. Esoh ◽  
Tobias O. Apinjoh ◽  
Steven G. Nyanjom ◽  
Ambroise Wonkam ◽  
Emile R. Chimusa ◽  
...  
Keyword(s):  
Genetic Structure ◽  
Ethnic Groups ◽  
Genetic Association ◽  
Association Studies ◽  
Genetic Association Studies ◽  
Genomic Region ◽  
Sub Saharan Africa ◽  
Genome Wide Association Studies ◽  
Fine Scale ◽  
Sub Saharan

AbstractInferences from genetic association studies rely largely on the definition and description of the underlying populations that highlight their genetic similarities and differences. The clustering of human populations into subgroups (population structure) can significantly confound disease associations. This study investigated the fine-scale genetic structure within Cameroon that may underlie disparities observed with Cameroonian ethnicities in malaria genome-wide association studies in sub-Saharan Africa. Genotype data of 1073 individuals from three regions and three ethnic groups in Cameroon were analyzed using measures of genetic proximity to ascertain fine-scale genetic structure. Model-based clustering revealed distinct ancestral proportions among the Bantu, Semi-Bantu and Foulbe ethnic groups, while haplotype-based coancestry estimation revealed possible longstanding and ongoing sympatric differentiation among individuals of the Foulbe ethnic group, and their Bantu and Semi-Bantu counterparts. A genome scan found strong selection signatures in the HLA gene region, confirming longstanding knowledge of natural selection on this genomic region in African populations following immense disease pressure. Signatures of selection were also observed in the HBB gene cluster, a genomic region known to be under strong balancing selection in sub-Saharan Africa due to its co-evolution with malaria. This study further supports the role of evolution in shaping genomes of Cameroonian populations and reveals fine-scale hierarchical structure among and within Cameroonian ethnicities that may impact genetic association studies in the country.

scholarly journals Genomic basis of striking fin shapes and colours in the fighting fish

2021 ◽  
Author(s):  
Le Wang ◽  
Fei Sun ◽  
Zi Yi Wan ◽  
Baoqing Ye ◽  
Yanfei Wen ◽  
...  
Keyword(s):  
Evolutionary Biology ◽  
Association Studies ◽  
Regulatory Element ◽  
Regulatory Elements ◽  
Major Effect ◽  
Betta Splendens ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
Phenotypic Variations ◽  
Genomic Basis

Abstract Resolving the genomic basis underlying phenotypic variations is a question of great importance in evolutionary biology. However, understanding how genotypes determine the phenotypes is still challenging. Centuries of artificial selective breeding for beauty and aggression resulted in a plethora of colors, long fin varieties, and hyper-aggressive behavior in the air-breathing Siamese fighting fish (Betta splendens), supplying an excellent system for studying the genomic basis of phenotypic variations. Combining whole genome sequencing, QTL mapping, genome-wide association studies and genome editing, we investigated the genomic basis of huge morphological variation in fins and striking differences in coloration in the fighting fish. Results revealed that the double tail, elephant ear, albino and fin spot mutants each were determined by single major-effect loci. The elephant ear phenotype was likely related to differential expression of a potassium ion channel gene, kcnh8. The albinotic phenotype was likely linked to a cis-regulatory element acting on the mitfa gene and the double tail mutant was suggested to be caused by a deletion in a zic1/zic4 co-enhancer. Our data highlight that major loci and cis-regulatory elements play important roles in bringing about phenotypic innovations and establish Bettas as new powerful model to study the genomic basis of evolved changes.

scholarly journals Integration of genome wide association studies and whole genome sequencing provides novel insights into fat deposition in chicken

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Gabriel Costa Monteiro Moreira ◽  
Clarissa Boschiero ◽  
Aline Silva Mello Cesar ◽  
James M. Reecy ◽  
Thaís Fernanda Godoy ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Association Studies ◽  
Fat Deposition ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Whole Genome ◽  
Genome Wide

scholarly journals High Resolution Ancestry Deconvolution for Next Generation Genomic Data

2021 ◽  
Author(s):  
Helgi Hilmarsson ◽  
Arvind S. Kumar ◽  
Richa Rastogi ◽  
Carlos D. Bustamante ◽  
Daniel Mas Montserrat ◽  
...  
Keyword(s):  
High Resolution ◽  
Prediction Models ◽  
Association Studies ◽  
Training Data ◽  
Genome Wide Association Studies ◽  
Whole Genome ◽  
Next Generation ◽  
Genome Data ◽  
Computational Performance ◽  
Genetic Risk Prediction

ABSTRACTAs genome-wide association studies and genetic risk prediction models are extended to globally diverse and admixed cohorts, ancestry deconvolution has become an increasingly important tool. Also known as local ancestry inference (LAI), this technique identifies the ancestry of each region of an individual’s genome, thus permitting downstream analyses to account for genetic effects that vary between ancestries. Since existing LAI methods were developed before the rise of massive, whole genome biobanks, they are computationally burdened by these large next generation datasets. Current LAI algorithms also fail to harness the potential of whole genome sequences, falling well short of the accuracy that such high variant densities can enable. Here we introduce Gnomix, a set of algorithms that address each of these points, achieving higher accuracy and swifter computational performance than any existing LAI method, while also enabling portable models that are particularly useful when training data are not shareable due to privacy or other restrictions. We demonstrate Gnomix (and its swift phase correction counterpart Gnofix) on worldwide whole-genome data from both humans and canids and utilize its high resolution accuracy to identify the location of ancient New World haplotypes in the Xoloitzcuintle, dating back over 100 generations. Code is available at https://github.com/AI-sandbox/gnomix.

scholarly journals Scalability and cost-effectiveness analysis of whole genome-wide association studies on Google Cloud Platform and Amazon Web Services

2020 ◽  
Vol 27 (9) ◽  
pp. 1425-1430
Author(s):  
Inès Krissaane ◽  
Carlos De Niz ◽  
Alba Gutiérrez-Sacristán ◽  
Gabor Korodi ◽  
Nneka Ede ◽  
...  
Keyword(s):  
Web Services ◽  
Association Studies ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Whole Genome ◽  
Cloud Platform ◽  
Human Genomics ◽  
Genome Wide ◽  
Innovative Methodology ◽  
Amazon Web Services

Abstract Objective Advancements in human genomics have generated a surge of available data, fueling the growth and accessibility of databases for more comprehensive, in-depth genetic studies. Methods We provide a straightforward and innovative methodology to optimize cloud configuration in order to conduct genome-wide association studies. We utilized Spark clusters on both Google Cloud Platform and Amazon Web Services, as well as Hail (http://doi.org/10.5281/zenodo.2646680) for analysis and exploration of genomic variants dataset. Results Comparative evaluation of numerous cloud-based cluster configurations demonstrate a successful and unprecedented compromise between speed and cost for performing genome-wide association studies on 4 distinct whole-genome sequencing datasets. Results are consistent across the 2 cloud providers and could be highly useful for accelerating research in genetics. Conclusions We present a timely piece for one of the most frequently asked questions when moving to the cloud: what is the trade-off between speed and cost?

scholarly journals Frameshift Variant in Novel Adenosine-A1-Receptor Homolog Associated With Bovine Spastic Syndrome/Late-Onset Bovine Spastic Paresis in Holstein Sires

2020 ◽  
Vol 11 ◽  
Author(s):  
Frederik Krull ◽  
Marc Hirschfeld ◽  
Wilhelm Ewald Wemheuer ◽  
Bertram Brenig
Keyword(s):  
Late Onset ◽  
Association Studies ◽  
Adenosine A1 Receptor ◽  
Genome Wide Association Studies ◽  
Whole Genome ◽  
Genome Resequencing ◽  
Adenosine A1 ◽  
Spastic Paresis ◽  
A1 Receptor ◽  
Whole Genome Resequencing

Since their first description almost 100 years ago, bovine spastic paresis (BSP) and bovine spastic syndrome (BSS) are assumed to be inherited neuronal-progressive diseases in cattle. Affected animals are characterized by (frequent) spasms primarily located in the hind limbs, accompanied by severe pain symptoms and reduced vigor, thus initiating premature slaughter or euthanasia. Due to the late onset of BSP and BSS and the massively decreased lifespan of modern cattle, the importance of these diseases is underestimated. In the present study, BSP/BSS-affected German Holstein breeding sires from artificial insemination centers were collected and pedigree analysis, genome-wide association studies, whole genome resequencing, protein–protein interaction network analysis, and protein-homology modeling were performed to elucidate the genetic background. The analysis of 46 affected and 213 control cattle revealed four significantly associated positions on chromosome 15 (BTA15), i.e., AC_000172.1:g.83465449A>G (–log10P = 19.17), AC_000172.1:g.81871849C>T (–log10P = 8.31), AC_000172.1:g.81872621A>T (–log10P = 6.81), and AC_000172.1:g.81872661G>C (–log10P = 6.42). Two additional loci were significantly associated located on BTA8 and BTA19, i.e., AC_000165.1:g.71177788T>C and AC_000176.1:g.30140977T>G, respectively. Whole genome resequencing of five affected individuals and six unaffected relatives (two fathers, two mothers, a half sibling, and a full sibling) belonging to three different not directly related families was performed. After filtering, a homozygous loss of function variant was identified in the affected cattle, causing a frameshift in the so far unknown gene locus LOC100848076 encoding an adenosine-A1-receptor homolog. An allele frequency of the variant of 0.74 was determined in 3,093 samples of the 1000 Bull Genomes Project.

scholarly journals Novel genetic determinants of telomere length from a trans-ethnic analysis of 109,122 whole genome sequences in TOPMed

2019 ◽  
Author(s):  
Margaret A Taub ◽  
Matthew P Conomos ◽  
Rebecca Keener ◽  
Kruthika R Iyer ◽  
Joshua S Weinstock ◽  
...  
Keyword(s):  
Telomere Length ◽  
Association Studies ◽  
P Value ◽  
Genome Wide Association Studies ◽  
Whole Genome ◽  
Genetic Determinants ◽  
Age Related ◽  
Genome Wide ◽  
Variant Genotype ◽  
Effect Heterogeneity

ABSTRACTTelomeres shorten in replicating somatic cells, and telomere length (TL) is associated with age-related diseases 1,2. To date, 17 genome-wide association studies (GWAS) have identified 25 loci for leukocyte TL 3–19, but were limited to European and Asian ancestry individuals and relied on laboratory assays of TL. In this study from the NHLBI Trans-Omics for Precision Medicine (TOPMed) program, we used whole genome sequencing (WGS) of whole blood for variant genotype calling and the bioinformatic estimation of TL in n=109,122 trans-ethnic (European, African, Asian and Hispanic/Latino) individuals. We identified 59 sentinel variants (p-value <5×10−9) from 36 loci (20 novel, 13 replicated in external datasets). There was little evidence of effect heterogeneity across populations, and 10 loci had >1 independent signal. Fine-mapping at OBFC1 indicated the independent signals colocalized with cell-type specific eQTLs for OBFC1 (STN1). We further identified two novel genes, DCLRE1B (SNM1B) and PARN, using a multi-variant gene-based approach.

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