Pedigree reconstruction and distant pairwise relatedness estimation from genome sequence data: A demonstration in a population of rhesus macaques (Macaca mulatta)

Abstract

A primary challenge in the analysis of free‐ranging animal populations is the accurate estimation of relatedness among individuals. Many aspects of population analysis rely on knowledge of relatedness patterns, including socioecology, demography, heritability and gene mapping analyses, wildlife conservation and the management of breeding colonies. Methods for determining relatedness using genome‐wide data have improved our ability to determine kinship and reconstruct pedigrees in humans. However, methods for reconstructing complex pedigree structures and estimating distant relatedness (beyond third‐degree) have not been widely applied to other species. We sequenced the genomes of 150 male rhesus macaques from the Tulane National Primate Research Center colony to estimate pairwise relatedness, reconstruct closely related pedigrees, estimate more distant relationships and augment colony records. Methods for determining relatedness developed for human genetic data were applied and evaluated in the analysis of nonhuman primates, including identity‐by‐descent‐based methods for pedigree reconstruction and shared segment‐based inference of more distant relatedness. We compared the genotype‐based pedigrees and estimated relationships to available colony pedigree records and found high concordance (95.5% agreement) between expected and identified relationships for close relatives. In addition, we detected distant relationships not captured in colony records, including some as distant as twelfth‐degree. Furthermore, while deep sequence coverage is preferable, we show that this approach can also provide valuable information when only low‐coverage (5×) sequence data is available. Our findings demonstrate the value of these methods for determination of relatedness in various animal populations, with diverse applications to conservation biology, evolutionary and ecological research and biomedical studies.

Genomic resources for rhesus macaques (Macaca mulatta)

“…There are multiple different applications for information regarding genetic variation in rhesus populations, including studies of population genetics (Hernandez et al 2007 ; Liu et al 2018 ), analyses of the genetic causes of macaque pathology relevant to human disease (Bimber et al 2017 ; Dray et al 2018 ; Moshiri et al 2019 ; Peterson et al 2019 ; Rogers et al 2013 ), applications of genetic markers to assist in the genetic management of captive breeding colonies (Kanthaswamy et al 2014 , 2006 ; Petty et al 2021 ; Smith 1980 , 1982 ), or studies of functional variation influencing normal (non-pathogenic) phenotypic diversity (Warren et al 2020 ). Furthermore, while SNVs are the most common type of polymorphism in the macaque genome, gene copy number variants, structural variation, and other types of insertion/deletion polymorphisms may account for a larger number of affected base pairs.…”

Editorial 2022

“…Top resources published in Molecular Ecology Resources in 2021 include key contributions across multiple subject areas, with the following articles selected by editors of the journal. Amongst the top Computer Programs and R packages published by the journal are “DILS: Demographic inferences with linked selection” (Fraïsse et al, 2021), which provides an easy to use interface and powerful machine learning methods to select the most appropriate demographic model to understand speciation from population genomic data; “SambaR: An R package for fast, easy and reproducible population‐genetic analyses of biallelic SNP data sets” (de Jong et al, 2021), a user‐friendly R package which allows for fast population genetic analyses on biallelic SNP data and provides a useful platform for SNP data storage, and “Pedigree reconstruction and distant pairwise relatedness estimation from genome sequence data: A demonstration in a population of rhesus macaques ( Macaca mulatta )”, (Petty et al, 2021), which presents a method to infer both pedigree relationships and distant pairwise relatedness estimates from non‐human whole genome data.…”

Taking identity-by-descent analysis into the wild: Estimating realized relatedness in free-ranging macaques

“…The total fraction of the genome IBD between two individuals is, in principle, the most precise method to estimate kinship [36][37][38] , as it corresponds to the exact fraction of shared DNA (i.e., realized relatedness) 10,[39][40][41][42][43] . Because distant relatives share fewer and shorter IBD segments than close relatives (as more recombination separates them from their common ancestors) [44][45][46][47] , the number and size distribution of IBD segments also provides additional information about pedigree relationships beyond that contained in mean IBD alone. This information can be very fine-grained: for example, in cases where recombination rates differ in female versus male germline cells, the number of shared segments is also expected to differ between maternal and paternal kin of the same degree 48,49 .…”

“…While these initial successful applications are encouraging, they underscore the necessity for systematic testing on a population possessing a known pedigree to solidify this method as a reliable approach for estimating realized relatedness in nonhuman animals. They also relied on highly accurate genotype calls from moderate to high-coverage sequencing or other genome-wide genotyping platforms 47,62,63 . These approaches remain infeasible for many natural populations, where recent efforts to generate comprehensive genotyping data sets have focused instead on low-coverage resequencing 32,33 .…”

“…For example, IBD-based methods enable precise detection of relatedness structure, migration, and mating patterns even in previously unstudied populations 57,58 . However, IBD-based methods have rarely been applied outside of humans (but see for dairy cows 59 , maize 60 , captive rhesus macaques 47 , Plasmodium 61 ). In natural populations, studies to date have typically either summarized IBD genome-wide or focused only on IBD within individuals (i.e., to identify runs of homozygosity indicative of inbreeding) 34,[62][63][64][65] .…”