Related papers: A complete classification of epistatic two-locus m…
There are 512 two-locus, two-allele, two-phenotype, fully-penetrant disease models. Using the permutation between two alleles, between two loci, and between being affected and unaffected, one model can be considered to be equivalent to…
Rapid research progress in genotyping techniques have allowed large genome-wide association studies. Existing methods often focus on determining associations between single loci and a specific phenotype. However, a particular phenotype is…
In statistical genetics an important task involves building predictive models for the genotype-phenotype relationships and thus attribute a proportion of the total phenotypic variance to the variation in genotypes. Numerous models have been…
Genome-wide epistasis analysis is a powerful tool to infer gene interactions, which can guide drug and vaccine development and lead to a deeper understanding of microbial pathogenesis. We have considered all complete SARS-CoV-2 genomes…
Recombinant Inbred Lines derived from divergent parental lines can display extensive segregation distortion and long-range linkage disequilibrium (LD) between distant loci. These genomic signatures are consistent with epistatic selection…
The evolutionary effect of recombination depends crucially on the epistatic interactions between linked loci. A paradigmatic case where recombination is known to be strongly disadvantageous is a two-locus fitness landscape dis- playing…
Epilepsy is one of the most common neurological disorders that can be diagnosed through electroencephalogram (EEG), in which the following epileptic events can be observed: pre-ictal, ictal, post-ictal, and interictal. In this paper, we…
2 Diabetes is a leading worldwide public health concern, and its increasing prevalence has significant health and economic importance in all nations. The condition is a multifactorial disorder with a complex aetiology. The genetic…
Genetic association studies, in particular the genome-wide association study design, have provided a wealth of novel insights into the aetiology of a wide range of human diseases and traits. The next challenge consists of understanding the…
We investigate a statistical model for multidimensional epistasis. The genotype is devided into subsequences, and within each subsequence mutations which occur in a prescribed order are beneficial. The bit-string model used to represent the…
The relationship between the shape of a fitness landscape and the underlying gene interactions, or epistasis, has been extensively studied in the two-locus case. Gene interactions among multiple loci are usually reduced to two-way…
We show that higher order epistasis has a substantial impact on evolutionary dynamics by analyzing peaks in the fitness landscapes. There are 193,270,310 fitness graphs, or cube orientations, for 4-locus systems, distributed on 511, 863…
To date, most genetic analyses of phenotypes have focused on analyzing single traits or, analyzing each phenotype independently. However, joint epistasis analysis of multiple complementary traits will increase statistical power, and hold…
Biochemical and regulatory interactions central to biological networks are expected to cause extensive genetic interactions or epistasis affecting the heritability of complex traits and the distribution of genotypes in populations. However,…
Epistasis is a phenomenon in which a phenotype outcome is determined by the interaction of genetic variation at two or more loci and it cannot be attributed to the additive combination of effects corresponding to the individual loci.…
We use Direct Coupling Analysis (DCA) to determine epistatic interactions between loci of variability of the SARS-CoV-2 virus, segmenting genomes by month of sampling. We use full-length, high-quality genomes from the GISAID repository up…
Genetic interactions can strongly influence the fitness effects of individual mutations, yet the impact of these epistatic interactions on evolutionary dynamics remains poorly understood. Here we investigate the evolutionary role of…
We introduce a data-driven epistatic model of protein evolution, capable of generating evolutionary trajectories spanning very different time scales reaching from individual mutations to diverged homologs. Our in silico evolution…
Dominance is usually considered a constant value that describes the relative difference in fitness or phenotype between heterozygotes and the average of homozygotes at a focal polymorphic locus. However, the observed dominance can vary with…
Although many phenotypic traits are determined by a large number of genetic variants, the behavior of allele frequencies in a polygenic trait is not completely understood. The problem is especially challenging when the quantitative trait of…