{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T02:03:29Z","timestamp":1772503409002,"version":"3.50.1"},"reference-count":46,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2024,11,5]],"date-time":"2024-11-05T00:00:00Z","timestamp":1730764800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Canada Research Chair in Genetics and Genealogy"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>In response to the current challenge in genetic studies to make new associations, we advocate for a shift toward leveraging population fine-scale structure. Our exploration brings to light distinct fine-structure within populations having undergone a founder effect such as the Ashkenazi Jews and the population of the Quebec\u2019 province. We leverage the fine-scale population structure to explore its impact on the frequency of rare variants. Notably, we observed an 8-fold increase in frequency for a variant associated with the Usher syndrome in one Quebec subpopulation. Our study underscores that smaller cohorts with greater genetic similarity demonstrate an important increase in rare variant frequencies, offering a promising avenue for new genetic variants\u2019 discovery.<\/jats:p>","DOI":"10.1371\/journal.pone.0313133","type":"journal-article","created":{"date-parts":[[2024,11,5]],"date-time":"2024-11-05T13:27:44Z","timestamp":1730813264000},"page":"e0313133","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":6,"title":["Fine-scale genetic structure and rare variant frequencies"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-9920-997X","authenticated-orcid":true,"given":"Laurence","family":"Gagnon","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia","family":"Moreau","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5526-9945","authenticated-orcid":true,"given":"Catherine","family":"Laprise","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4089-2280","authenticated-orcid":true,"given":"Simon L.","family":"Girard","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2024,11,5]]},"reference":[{"issue":"12","key":"pone.0313133.ref001","doi-asserted-by":"crossref","first-page":"961","DOI":"10.21037\/atm-21-1635","article-title":"Rare variants: data types and analysis strategies.","volume":"9","author":"C Goswami","year":"2021","journal-title":"Ann Transl Med."},{"key":"pone.0313133.ref002","article-title":"Recent advances and challenges of rare variant association analysis in the biobank sequencing era.","volume":"13","author":"W Chen","year":"2022","journal-title":"Front Genet."},{"issue":"9","key":"pone.0313133.ref003","doi-asserted-by":"crossref","first-page":"e1003815","DOI":"10.1371\/journal.pgen.1003815","article-title":"Whole-exome sequencing reveals a rapid change in the frequency of rare functional variants in a founding population of humans.","volume":"9","author":"F Casals","year":"2013","journal-title":"PLoS Genet"},{"issue":"9","key":"pone.0313133.ref004","doi-asserted-by":"crossref","first-page":"1465","DOI":"10.1016\/j.neuron.2021.03.004","article-title":"Novel ultra-rare exonic variants identified in a founder population implicate cadherins in schizophrenia","volume":"109","author":"T Lencz","year":"2021","journal-title":"Neuron"},{"issue":"1","key":"pone.0313133.ref005","doi-asserted-by":"crossref","first-page":"15606","DOI":"10.1038\/ncomms15606","article-title":"Whole genome sequencing and imputation in isolated populations identify genetic associations with medically-relevant complex traits","volume":"8","author":"L Southam","year":"2017","journal-title":"Nat Commun"},{"key":"pone.0313133.ref006","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1146\/annurev.genom.2.1.69","article-title":"Human Genetics: Lessons from Quebec Populations.","volume":"2","author":"CR Scriver","year":"2001","journal-title":"Annual Review of Genomics and Human Genetics"},{"issue":"1","key":"pone.0313133.ref007","doi-asserted-by":"crossref","first-page":"R2","DOI":"10.1186\/gb-2012-13-1-r2","article-title":"Implications for health and disease in the genetic signature of the Ashkenazi Jewish population","volume":"13","author":"S Guha","year":"2012","journal-title":"Genome Biology"},{"issue":"1","key":"pone.0313133.ref008","doi-asserted-by":"crossref","first-page":"4835","DOI":"10.1038\/ncomms5835","article-title":"Sequencing an Ashkenazi reference panel supports population-targeted personal genomics and illuminates Jewish and European origins","volume":"5","author":"S Carmi","year":"2014","journal-title":"Nat Commun"},{"issue":"3","key":"pone.0313133.ref009","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1086\/519795","article-title":"PLINK: A Tool Set for Whole-Genome Association and Population-Based Linkage Analyses","volume":"81","author":"S Purcell","year":"2007","journal-title":"Am J Hum Genet"},{"issue":"1","key":"pone.0313133.ref010","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1111\/1755-0998.12708","article-title":"Effects of sampling close relatives on some elementary population genetics analyses","volume":"18","author":"J. 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