scholarly journals A continent-wide high genetic load in African buffalo revealed by clines in the frequency of deleterious alleles, genetic hitchhiking and linkage disequilibrium

PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0259685
Author(s):  
Pim van Hooft ◽  
Wayne M. Getz ◽  
Barend J. Greyling ◽  
Bas Zwaan ◽  
Armanda D. S. Bastos
Keyword(s):  
Linkage Disequilibrium ◽  
Genetic Load ◽  
Male Body ◽  
African Buffalo ◽  
Latitude Range ◽  
Deleterious Alleles ◽  
Genome Wide ◽  
High Fraction ◽  
Frequency Occurrence ◽  
Microsatellite Alleles

A high genetic load can negatively affect population viability and increase susceptibility to diseases and other environmental stressors. Prior microsatellite studies of two African buffalo (Syncerus caffer) populations in South Africa indicated substantial genome-wide genetic load due to high-frequency occurrence of deleterious alleles. The occurrence of these alleles, which negatively affect male body condition and bovine tuberculosis resistance, throughout most of the buffalo’s range were evaluated in this study. Using available microsatellite data (2–17 microsatellite loci) for 1676 animals from 34 localities (from 25°S to 5°N), we uncovered continent-wide frequency clines of microsatellite alleles associated with the aforementioned male traits. Frequencies decreased over a south-to-north latitude range (average per-locus Pearson r = -0.22). The frequency clines coincided with a multilocus-heterozygosity cline (adjusted R2 = 0.84), showing up to a 16% decrease in southern Africa compared to East Africa. Furthermore, continent-wide linkage disequilibrium (LD) at five linked locus pairs was detected, characterized by a high fraction of positive interlocus associations (0.66, 95% CI: 0.53, 0.77) between male-deleterious-trait-associated alleles. Our findings suggest continent-wide and genome-wide selection of male-deleterious alleles driven by an earlier observed sex-chromosomal meiotic drive system, resulting in frequency clines, reduced heterozygosity due to hitchhiking effects and extensive LD due to male-deleterious alleles co-occurring in haplotypes. The selection pressures involved must be high to prevent destruction of allele-frequency clines and haplotypes by LD decay. Since most buffalo populations are stable, these results indicate that natural mammal populations, depending on their genetic background, can withstand a high genetic load.

scholarly journals When is selection effective?

2014 ◽  
Author(s):  
Simon Gravel
Keyword(s):  
Genetic Load ◽  
Human Populations ◽  
Deleterious Alleles ◽  
Genome Wide ◽  
Biological Insight ◽  
Specific Allele ◽  
Mutational Damage ◽  
Modelling Assumptions ◽  
Random Fluctuations ◽  
Quantitative Explanation

AbstractDeleterious alleles can reach high frequency in small populations because of random fluctuations in allele frequency. This may lead, over time, to reduced average fitness. In that sense, selection is more ‘effective’ in larger populations. Recent studies have considered whether the different demographic histories across human populations have resulted in differences in the number, distribution, and severity of deleterious variants, leading to an animated debate. This article first seeks to clarify some terms of the debate by identifying differences in definitions and assumptions used in recent studies. We argue that variants of Morton, Crow and Muller’s ‘total mutational damage’ provide the soundest and most practical basis for such comparisons. Using simulations, analytical calculations, and 1000 Genomes data, we provide an intuitive and quantitative explanation for the observed similarity in genetic load across populations. We show that recent demography has likely modulated the effect of selection, and still affects it, but the net result of the accumulated differences is small. Direct observation of differential efficacy of selection for specific allele classes is nevertheless possible with contemporary datasets. By contrast, identifying average genome-wide differences in the efficacy of selection across populations will require many modelling assumptions, and is unlikely to provide much biological insight about human populations.

scholarly journals Negative linkage disequilibrium between amino acid changing variants reveals interference among deleterious mutations in the human genome

2020 ◽  
Author(s):  
Jesse A. Garcia ◽  
Kirk E. Lohmueller
Keyword(s):  
Linkage Disequilibrium ◽  
Human Genome ◽  
Natural Populations ◽  
Physical Distance ◽  
Deleterious Mutations ◽  
High Coverage ◽  
Recessive Mutations ◽  
Deleterious Alleles ◽  
Genome Wide ◽  
Negative Epistasis

AbstractWhile there has been extensive work on patterns of linkage disequilibrium (LD) for neutral loci, the extent to which negative selection impacts LD is less clear. Forces like Hill-Robertson interference and negative epistasis are expected to lead to deleterious mutations being found on distinct haplotypes. However, the extent to which these forces depend on the selection and dominance coefficients of deleterious mutations and shape genome-wide patterns of LD in natural populations with complex demographic histories has not been tested. In this study, we first used forward-in-time simulations to generate predictions as to how selection impacts LD. Under models where deleterious mutations have additive effects on fitness, deleterious variants less than 10 kb apart tend to be carried on different haplotypes, generating an excess of negative LD relative to pairs of synonymous SNPs. In contrast, for recessive mutations, there is no consistent ordering of how selection coefficients affect r2 decay. We then examined empirical data of modern humans from the 1000 Genomes Project. LD between derived nonsynonymous SNPs is more negative compared to pairs of derived synonymous variants. This result holds when matching SNPs for frequency in the sample (allele count), physical distance, magnitude of background selection, and genetic distance between pairs of variants, suggesting that this result is not due to these potential confounding factors. Lastly, we introduce a new statistic HR(j) which allows us to detect interference using unphased genotypes. Application of this approach to high-coverage human genome sequences confirms our finding that deleterious alleles tend to be located on different haplotypes more often than are neutral alleles. Our findings suggest that either interference or negative epistasis plays a pervasive role in shaping patterns of LD between deleterious variants in the human genome, and consequently influencing genome-wide patterns of LD.

Genome-wide linkage disequilibrium in two Japanese beef cattle breeds

2006 ◽  
Vol 37 (2) ◽  
pp. 139-144 ◽  
Author(s):  
M. Odani ◽  
A. Narita ◽  
T. Watanabe ◽  
K. Yokouchi ◽  
Y. Sugimoto ◽  
...  
Keyword(s):  
Linkage Disequilibrium ◽  
Beef Cattle ◽  
Cattle Breeds ◽  
Genome Wide ◽  
Beef Cattle Breeds ◽  
Genome Wide Linkage Disequilibrium

scholarly journals Genome-wide evaluation of genetic diversity and linkage disequilibrium in winter and spring triticale (x Triticosecale Wittmack)

BMC Genomics ◽  
2012 ◽  
Vol 13 (1) ◽  
pp. 235 ◽  
Author(s):  
Katharina V Alheit ◽  
Hans Maurer ◽  
Jochen C Reif ◽  
Matthew R Tucker ◽  
Volker Hahn ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Linkage Disequilibrium ◽  
X Triticosecale ◽  
Genome Wide ◽  
Spring Triticale ◽  
Triticosecale Wittmack ◽  
X Triticosecale Wittmack

scholarly journals Challenges of Adjusting Single-Nucleotide Polymorphism Effect Sizes for Linkage Disequilibrium

2021 ◽  
pp. 1-11
Author(s):  
Valentina Escott-Price ◽  
Karl Michael Schmidt
Keyword(s):  
Linkage Disequilibrium ◽  
Association Studies ◽  
Statistical Significance ◽  
Ordinary Least Squares ◽  
Effect Sizes ◽  
Risk Scores ◽  
Genome Wide Association Studies ◽  
Single Nucleotide ◽  
Genome Wide ◽  
Tikhonov Regularisation

<b><i>Background:</i></b> Genome-wide association studies (GWAS) were successful in identifying SNPs showing association with disease, but their individual effect sizes are small and require large sample sizes to achieve statistical significance. Methods of post-GWAS analysis, including gene-based, gene-set and polygenic risk scores, combine the SNP effect sizes in an attempt to boost the power of the analyses. To avoid giving undue weight to SNPs in linkage disequilibrium (LD), the LD needs to be taken into account in these analyses. <b><i>Objectives:</i></b> We review methods that attempt to adjust the effect sizes (β<i>-</i>coefficients) of summary statistics, instead of simple LD pruning. <b><i>Methods:</i></b> We subject LD adjustment approaches to a mathematical analysis, recognising Tikhonov regularisation as a framework for comparison. <b><i>Results:</i></b> Observing the similarity of the processes involved with the more straightforward Tikhonov-regularised ordinary least squares estimate for multivariate regression coefficients, we note that current methods based on a Bayesian model for the effect sizes effectively provide an implicit choice of the regularisation parameter, which is convenient, but at the price of reduced transparency and, especially in smaller LD blocks, a risk of incomplete LD correction. <b><i>Conclusions:</i></b> There is no simple answer to the question which method is best, but where interpretability of the LD adjustment is essential, as in research aiming at identifying the genomic aetiology of disorders, our study suggests that a more direct choice of mild regularisation in the correction of effect sizes may be preferable.

scholarly journals GWAS revealed effect of genotype × environment interactions for grain yield of Nebraska winter wheat

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Shamseldeen Eltaher ◽  
P. Stephen Baenziger ◽  
Vikas Belamkar ◽  
Hamdy A. Emara ◽  
Ahmed A. Nower ◽  
...  
Keyword(s):  
Linkage Disequilibrium ◽  
Winter Wheat ◽  
Grain Yield ◽  
Genome Wide Association Study ◽  
Phenotypic Selection ◽  
Wheat Breeding ◽  
Wheat Genotypes ◽  
Genome Wide ◽  
Genomic Regions ◽  
Significant Linkage

Abstract Background Improving grain yield in cereals especially in wheat is a main objective for plant breeders. One of the main constrains for improving this trait is the G × E interaction (GEI) which affects the performance of wheat genotypes in different environments. Selecting high yielding genotypes that can be used for a target set of environments is needed. Phenotypic selection can be misleading due to the environmental conditions. Incorporating information from phenotypic and genomic analyses can be useful in selecting the higher yielding genotypes for a group of environments. Results A set of 270 F3:6 wheat genotypes in the Nebraska winter wheat breeding program was tested for grain yield in nine environments. High genetic variation for grain yield was found among the genotypes. G × E interaction was also highly significant. The highest yielding genotype differed in each environment. The correlation for grain yield among the nine environments was low (0 to 0.43). Genome-wide association study revealed 70 marker traits association (MTAs) associated with increased grain yield. The analysis of linkage disequilibrium revealed 16 genomic regions with a highly significant linkage disequilibrium (LD). The candidate parents’ genotypes for improving grain yield in a group of environments were selected based on three criteria; number of alleles associated with increased grain yield in each selected genotype, genetic distance among the selected genotypes, and number of different alleles between each two selected parents. Conclusion Although G × E interaction was present, the advances in DNA technology provided very useful tools and analyzes. Such features helped to genetically select the highest yielding genotypes that can be used to cross grain production in a group of environments.

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