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Long-read structural variant discovery and targeted short read genotyping enables population scale characterization of structural variation in rhesus macaques

Title: Long-read structural variant discovery and targeted short read genotyping enables population scale characterization of structural variation in rhesus macaques
Authors: Karina Ray; Christina Mulch; Samuel M. Peterson; Sebastian Benjamin; Nathan Gullicksrud; Adam J. Ericsen; Eric J. Vallender; Betsy M. Ferguson; Jeffrey D. Wall; Benjamin N. Bimber
Source: Genome Biology, Vol 26, Iss 1, Pp 1-19 (2025)
Publisher Information: BMC, 2025.
Publication Year: 2025
Collection: LCC:Biology (General); LCC:Genetics
Subject Terms: Biology (General); QH301-705.5; Genetics; QH426-470
Description: Abstract Background Due to their close evolutionary relationship with humans, rhesus macaques are an important pre-clinical model. While genetic diversity driven by short nucleotide variation has long been studied in rhesus macaques, there is comparatively little known about structural variation, with most published studies focused on cross-species comparative analyses. Understanding the degree and implications of intraspecies structural variation is essential to all biomedical research using rhesus macaques as a model. Results Here we present long-read sequencing of 59 rhesus macaques, identifying a catalog of 339,334 structural variants (SVs), which we subsequently genotype in a cohort of 2,645 individuals with short read whole genome sequencing data to create the largest public dataset of rhesus macaque SVs. These data reveal population structure within rhesus macaque SVs based on both geographic ancestry and to a lesser degree, breeding center. While there is evidence of strong purifying selection against SVs within exons, 0.7% of SVs overlap exons, with an average of 16.9 rare SVs per subject predicted to have a high impact on protein coding sequences. Notably, rhesus macaque SVs are dominated by Alu retrotransposition events, which comprise 55.7% of SVs and suggest significantly different modes of SV formation relative to humans and great apes. Conclusions This dataset represents the largest study of structural variation in rhesus macaques to date and demonstrates use of both long and short-read datasets to generate SV genotype data. These data enable the consideration of structural variation impact in rhesus macaque-based research and will also aid the development of primate pangenomes.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 1474-760X
Relation: https://doaj.org/toc/1474-760X
DOI: 10.1186/s13059-025-03873-3
Access URL: https://doaj.org/article/8ff7b50f4eef49959cc4cd947005e1c4
Accession Number: edsdoj.8ff7b50f4eef49959cc4cd947005e1c4
Database: Directory of Open Access Journals