{"doi":"10.1101/2022.03.02.482700","title":"A novel quantitative trait locus implicates <i>Msh3</i> in the propensity for genome-wide short tandem repeat expansions in mice","abstract":"Abstract Short tandem repeats (STRs) are a class of rapidly mutating genetic elements characterized by repeated units of 1 or more nucleotides. We leveraged whole genome sequencing data for 152 recombinant inbred (RI) strains from the BXD family derived from C57BL/6J and DBA/2J mice to study the effects of genetic background on genome-wide patterns of new mutations at STRs. We defined quantitative phenotypes describing the numbers and types of germline STR mutations in each strain and identified a locus on chromosome 13 associated with the propensity of STRs to expand. Several dozen genes lie in the QTL region, including Msh3 , a known modifier of STR stability at pathogenic repeat expansions in mice and humans. Detailed analysis of the locus revealed a cluster of variants near the 5’ end of Msh3 , including multiple protein-coding variants within the DNA mismatch recognition domain of MSH3, and a retrotransposon insertion overlapping an annotated exon. Additionally, gene expression analysis demonstrates co-localization of this QTL with expression QTLs for multiple nearby genes, including Msh3 . Our results suggest a novel role for Msh3 in regulating genome-wide patterns of germline STR mutations and demonstrate that inherited genetic variation can contribute to variability in accumulation of new mutations across individuals.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":299882,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9494,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":348388,"name":"David G. Ashbrook","orcid":"0000-0002-7397-8910","position":1,"is_corresponding":false},{"id":24559,"name":"Flavia Villani","orcid":"0000-0003-3633-0610","position":2,"is_corresponding":false},{"id":469971,"name":"Vincenza Colonna","orcid":"0000-0002-3966-0474","position":3,"is_corresponding":false},{"id":24592,"name":"Nima Mousavi","orcid":"0000-0003-1926-8982","position":4,"is_corresponding":false},{"id":622778,"name":"Nichole Ma","orcid":"0000-0003-4343-8689","position":5,"is_corresponding":false},{"id":230002,"name":"Abraham A. Palmer","orcid":"0000-0003-3634-0747","position":6,"is_corresponding":false},{"id":314350,"name":"Melissa Gymrek","orcid":"0000-0002-6086-3903","position":7,"is_corresponding":false},{"id":856133,"name":"Mikhail O. Maksimov","orcid":"0000-0001-9428-3424","position":0,"is_corresponding":true}],"reference_count":49,"raw_metadata":null,"created_at":"2026-07-19T00:31:49.412501Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}