Correspondence Between Genomic- and Genealogical/Coalescent-Based Inference of Homozygosity by Descent in Large French-Canadian Genealogies

Author:

Burkett Kelly M.,Rakesh Mohan,Morris Patricia,Vézina Hélène,Laprise Catherine,Freeman Ellen E.,Roy-Gagnon Marie-Hélène

Abstract

Research on the genetics of complex traits overwhelmingly focuses on the additive effects of genes. Yet, animal studies have shown that non-additive effects, in particular homozygosity effects, can shape complex traits. Recent investigations in human studies found some significant homozygosity effects. However, most human populations display restricted ranges of homozygosity by descent (HBD), making the identification of homozygosity effects challenging. Founder populations give rise to higher HBD levels. When deep genealogical data are available in a founder population, it is possible to gain information on the time to the most recent common ancestor (MRCA) from whom a chromosomal segment has been transmitted to both parents of an individual and in turn to that individual. This information on the time to MRCA can be combined with the time to MRCA inferred from coalescent models of gene genealogies. HBD can also be estimated from genomic data. The extent to which the genomic HBD measures correspond to the genealogical/coalescent measures has not been documented in founder populations with extensive genealogical data. In this study, we used simulations to relate genomic and genealogical/coalescent HBD measures. We based our simulations on genealogical data from two ongoing studies from the French-Canadian founder population displaying different levels of inbreeding. We simulated single-nucleotide polymorphisms (SNPs) in a 1-Mb genomic segment from a coalescent model in conjunction with the observed genealogical data. We compared genealogical/coalescent HBD to two genomic methods of HBD estimation based on hidden Markov models (HMMs). We found that genomic estimates of HBD correlated well with genealogical/coalescent HBD measures in both study genealogies. We described generation time to coalescence in terms of genomic HBD estimates and found a large variability in generation time captured by genomic HBD when considering each SNP. However, SNPs in longer segments were more likely to capture recent time to coalescence, as expected. Our study suggests that estimating the coalescent gene genealogy from the genomic data to use in conjunction with observed genealogical data could provide valuable information on HBD.

Publisher

Frontiers Media SA

Subject

Genetics (clinical),Genetics,Molecular Medicine

Reference45 articles.

1. Homogénéité ou diversité? L'histoire de la population du Québec revue à travers ses gènes;Bouchard;Histoire Soc.,1990

2. Markov Chain Monte Carlo Sampling of Gene Genealogies Conditional on Unphased SNP Genotype Data;Burkett;Stat. Appl. Genet. Mol. Biol.,2013

3. Sampletrees and Rsampletrees: Sampling Gene Genealogies Conditional on SNP Genotype Data;Burkett;Bioinformatics,2016

4. Runs of Homozygosity: Windows into Population History and Trait Architecture;Ceballos;Nat. Rev. Genet.,2018

5. Second-Generation PLINK: Rising to the Challenge of Larger and Richer Datasets;Chang;GigaSci,2015

Cited by 4 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3