Abstract
Simulations of close relatives and identical by descent (IBD) segments are common in genetic studies, yet most past efforts have utilized sex averaged genetic maps and ignored crossover interference, thus omitting features known to affect the breakpoints of IBD segments. We developed Ped-sim, a method for simulating relatives that can utilize either sex-specific or sex averaged genetic maps and also either a model of crossover interference or the traditional Poisson model for inter-crossover distances. To characterize the impact of previously ignored mechanisms, we simulated data for all four combinations of these factors. We found that modeling crossover interference decreases the standard deviation of pairwise IBD proportions by 10.4% on average in full siblings through second cousins. By contrast, sex-specific maps increase this standard deviation by 4.2% on average, and also impact the number of segments relatives share. Most notably, using sex-specific maps, the number of segments half-siblings share is bimodal; and when combined with interference modeling, the probability that sixth cousins have non-zero IBD sharing ranges from 9.0 to 13.1%, depending on the sexes of the individuals through which they are related. We present new analytical results for the distributions of IBD segments under these models and show they match results from simulations. Finally, we compared IBD sharing rates between simulated and real relatives and find that the combination of sex-specific maps and interference modeling most accurately captures IBD rates in real data. Ped-sim is open source and available from https://github.com/williamslab/ ped-sim.
| Original language | American English |
|---|---|
| Article number | e1007979 |
| Journal | PLoS Genetics |
| Volume | 15 |
| Issue number | 12 |
| DOIs | |
| State | Published - 2019 |
Bibliographical note
Funding Information:Support for this work was provided by National Institutes of Health grant R35 GM133805 (ALW); an Alfred P. Sloan Research Fellowship (ALW); a seed grant from Nancy and Peter Meinig (ALW); United States–Israel Binational Science Foundation grant 2017024 (SC); Israel Science Foundation grant 407/17 (SC); R01 HL0113323, P01 HL045222, R01 DK047482, and R01 DK053889 (TDD, DML, JEC, RD, and JB). MC and DNS were partially supported by National Institutes of Health grants T32 GM007617-37 and T32 GM083937, respectively. Funding for the Wellcome Trust Case-Control Consortium was provided by the Wellcome Trust under award 076113, 085475 and 090355. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Publisher Copyright:
© 2019 Caballero et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
