Linkage analysis of affected sib pairs allowing for parent-of-origin effects.
Parent-of-origin effects, also known as genomic imprinting, exist for many mammalian genes. For imprinted genes the expression of an allele depends upon the sex of the transmitting parent. Here we have developed a method based on alleles that are shared identical by descent by affected sib pairs, that allows for parent-of-origin effects. Our method allows for sex-specific recombination rates, an important consideration in studying imprinted genes. We have also derived a tetrahedron for the true identical-by-descent frequencies accounting for parent-of-origin effects. Using this tetrahedron, we propose a robust generalized minmax test for linkage and discuss its properties in the presence of genomic imprinting. We have also performed power comparisons of various allele sharing tests and provide regions of the tetrahedron in which the different tests are optimal. We also provide useful strategies to determine the optimal tests to use while performing a genome scan.
Wu
Chih-Chieh
CC
Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 189, Houston, TX 77030, USA. ccwu@mdanderson.org
Shete
Sanjay
S
Amos
Christopher I
CI
D000483:Alleles; D002874:Chromosome Mapping / Q000379:methods*; D005260:Female; D008040:Genetic Linkage; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease; D018392:Genomic Imprinting / Q000235:genetics*; D006801:Humans; D008126:Lod Score; D008297:Male; D008957:Models, Genetic; D010290:Parents; D019655:Quantitative Trait, Heritable; D035781:Siblings
D005819:Genetic Markers