Calculation of IBD probabilities with dense SNP or sequence data

被引:4
作者
Keith, Jonathan M. [1 ]
McRae, Allan [2 ]
Duffy, David [2 ]
Mengersen, Kerrie [1 ]
Visscher, Peter M. [2 ]
机构
[1] Queensland Univ Technol, Sch Math Sci, Brisbane, Qld 4001, Australia
[2] Royal Brisbane Hosp, Queensland Inst Med Res, Brisbane, Qld 4006, Australia
关键词
identity by descent; linkage disequilibrium; single nucleotide polymorphism;
D O I
10.1002/gepi.20324
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
The probabilities that two individuals share 0, 1, or 2 alleles identical by descent (IBD) at a given genotyped marker locus are quantities of fundamental importance for disease gene and quantitative trait mapping and in family-based tests of association. Until recently, genotyped markers were sufficiently sparse that founder haplotypes could be modelled as having been drawn from a population in linkage equilibrium for the purpose of estimating IBD probabilities. However, with the advent of high-throughput single nucleotide polymorphism genotyping assays, this is no longer a reasonable assumption. Indeed, the imminent arrival of individual sequencing will enable high-density single nucleotide polymorphism genotyping on a scale for which current algorithms are not equipped. In this paper, we present a simple new model in which founder haplotypes are modelled as a Markov chain. Another important innovation is that genotyping errors are explicitly incorporated into the model. We compare results obtained using the new model to those obtained using the popular genetic linkage analysis package Merlin, with and without using the cluster model of linkage disequilibrium that is incorporated into that program. We find that the new model results in accuracy approaching that of Merlin with haplotype blocks, but achieves this with orders of magnitude faster run times. Moreover, the new algorithm scales linearly with number of markers, irrespective of density, whereas Merlin scales supralinearly. We also confirm a previous finding that ignoring linkage disequilibrium in founder haplotypes can cause errors in the calculation of IBD probabilities.
引用
收藏
页码:513 / 519
页数:7
相关论文
共 27 条
[1]   Handling marker-marker linkage disequilibrium: Pedigree analysis with clustered markers [J].
Abecasis, GR ;
Wigginton, JE .
AMERICAN JOURNAL OF HUMAN GENETICS, 2005, 77 (05) :754-767
[2]   A general test of association for quantitative traits in nuclear families [J].
Abecasis, GR ;
Cardon, LR ;
Cookson, WOC .
AMERICAN JOURNAL OF HUMAN GENETICS, 2000, 66 (01) :279-292
[3]   Merlin-rapid analysis of dense genetic maps using sparse gene flow trees [J].
Abecasis, GR ;
Cherny, SS ;
Cookson, WO ;
Cardon, LR .
NATURE GENETICS, 2002, 30 (01) :97-101
[4]   Pedigree tests of transmission disequilibrium (Reprinted from European Journal of Human Genetics, Vol 8, pg 545-551,2000) [J].
Abecasis, Goncalo R. ;
Cookson, William O. C. ;
Cardon, Lon R. .
EUROPEAN JOURNAL OF HUMAN GENETICS, 2017, 25 :S40-S44
[5]   A haplotype map of the human genome [J].
Altshuler, D ;
Brooks, LD ;
Chakravarti, A ;
Collins, FS ;
Daly, MJ ;
Donnelly, P ;
Gibbs, RA ;
Belmont, JW ;
Boudreau, A ;
Leal, SM ;
Hardenbol, P ;
Pasternak, S ;
Wheeler, DA ;
Willis, TD ;
Yu, FL ;
Yang, HM ;
Zeng, CQ ;
Gao, Y ;
Hu, HR ;
Hu, WT ;
Li, CH ;
Lin, W ;
Liu, SQ ;
Pan, H ;
Tang, XL ;
Wang, J ;
Wang, W ;
Yu, J ;
Zhang, B ;
Zhang, QR ;
Zhao, HB ;
Zhao, H ;
Zhou, J ;
Gabriel, SB ;
Barry, R ;
Blumenstiel, B ;
Camargo, A ;
Defelice, M ;
Faggart, M ;
Goyette, M ;
Gupta, S ;
Moore, J ;
Nguyen, H ;
Onofrio, RC ;
Parkin, M ;
Roy, J ;
Stahl, E ;
Winchester, E ;
Ziaugra, L ;
Shen, Y .
NATURE, 2005, 437 (7063) :1299-1320
[6]   EVIDENCE FOR HL-A-LINKED GENES IN JUVENILE DIABETES-MELLITUS [J].
CUDWORTH, AG ;
WOODROW, JC .
BRITISH MEDICAL JOURNAL, 1975, 3 (5976) :133-135
[7]   GENERAL MODEL FOR GENETIC ANALYSIS OF PEDIGREE DATA [J].
ELSTON, RC ;
STEWART, J .
HUMAN HEREDITY, 1971, 21 (06) :523-&
[8]   International genome project launched [J].
Hayden, Erika Check .
NATURE, 2008, 451 (7177) :378-379
[9]   Markov chain Monte Carlo segregation and linkage analysis for oligogenic models [J].
Heath, SC .
AMERICAN JOURNAL OF HUMAN GENETICS, 1997, 61 (03) :748-760
[10]   Generating samples under a Wright-Fisher neutral model of genetic variation [J].
Hudson, RR .
BIOINFORMATICS, 2002, 18 (02) :337-338