Testing for genetic linkage in families by a variance-components approach in the presence of genomic imprinting.
Some genes that affect development and behavior in mammals are known to be imprinted; and > or = 1% of all mammalian genes are imprinted. Hence, incorporating an imprinting parameter into linkage analysis may increase the power to detect linkage for these traits. Here we propose theoretical justifications for a recently developed model for testing of linkage, in the presence of genetic imprinting, between a quantitative-trait locus and a polymorphic marker; this is achieved in the variance-components framework. We also incorporate sex-specific recombination fractions into this model. We discuss the effects that imprinting and nonimprinting have on the power of the usual variance-components method and on the variance-components method that incorporates an imprinting parameter. We provide noncentrality parameters that can be used to determine the sample size necessary to attain a specified power for a given significance level, which is useful in the planning of a linkage study. Optimal strategies for a genome scan of potentially imprinted traits are discussed.
Shete
Sanjay
S
Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA. sshete@mdanderson.org
Amos
Christopher I
CI
D000483:Alleles; D002874:Chromosome Mapping / Q000379:methods* / Q000706:statistics & numerical data; D005260:Female; D015894:Genome, Human; D018392:Genomic Imprinting / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008126:Lod Score; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics; D011336:Probability; D019655:Quantitative Trait, Heritable; D011995:Recombination, Genetic / Q000235:genetics; D018401:Sample Size