Mathematical assumptions versus biological reality: myths in affected sib pair linkage analysis

Am J Hum Genet. 2005 Jan;76(1):152-6. doi: 10.1086/426872. Epub 2004 Nov 11.

Abstract

Affected sib pair (ASP) analysis has become common ever since it was shown that, under very specific assumptions, ASPs afford a powerful design for linkage analysis. In 2003, Vieland and Huang, on the basis of a "fundamental heterogeneity equation," proved that heterogeneity and epistasis are confounded in ASP linkage analysis. A much more serious limitation of ASP linkage analysis is the implicit assumption that randomly sampled sib pairs share half their alleles identical by descent at any locus, whereas a critical assumption underlying Vieland and Huang's proof is that of joint Hardy-Weinberg equilibrium proportions at two trait loci. These are considered as examples of mathematical assumptions that may not always reflect biological reality. More-robust sib-pair designs and appropriate methods for their analysis have long been available.

Publication types

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

MeSH terms

  • Chromosome Mapping / methods*
  • Epistasis, Genetic
  • Genetic Heterogeneity
  • Genetic Linkage*
  • Humans
  • Models, Statistical*
  • Siblings