2022/01/09 by Diego Ortega‐Del Vecchyo, Kirk E. Lohmueller, John Novembre · 1 voice
Biochemistry, Genetics and Molecular Biology · #Evolution and Genetic Dynamics #Genetic Associations and Epidemiology #Genetic Mapping and Diversity in Plants and Animals
paper · pdf · doi:10.1093/genetics/iyac002
openalex publication_date 2022/01/09 · openalex created_date 2022/05/05 · openalex updated_date 2026/06/24
Recent genome sequencing studies with large sample sizes in humans have discovered a vast quantity of low-frequency variants, providing an important source of information to analyze how selection is acting on human genetic variation. In order to estimate the strength of natural selection acting on low-frequency variants, we have developed a likelihood-based method that uses the lengths of pairwise identity-by-state between haplotypes carrying low-frequency variants. We show that in some nonequilibrium populations (such as those that have had recent population expansions) it is possible to distinguish between positive or negative selection acting on a set of variants. With our new framework, one can infer a fixed selection intensity acting on a set of variants at a particular frequency, or a distribution of selection coefficients for standing variants and new mutations. We show an application of our method to the UK10K phased haplotype dataset of individuals.