Testing for genetic linkage in families by a variance-components approach in the presence of genomic imprinting

Am J Hum Genet. 2002 Mar;70(3):751-7. doi: 10.1086/338931. Epub 2002 Feb 8.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alleles
  • Chromosome Mapping / methods*
  • Chromosome Mapping / statistics & numerical data
  • Female
  • Genome, Human
  • Genomic Imprinting / genetics*
  • Genotype
  • Humans
  • Lod Score
  • Male
  • Polymorphism, Genetic / genetics
  • Probability
  • Quantitative Trait, Heritable
  • Recombination, Genetic / genetics
  • Sample Size