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SNPs and snails and puppy dogs' tails: analysis of SNP haplotype data using the gamete competition model

Published online by Cambridge University Press:  09 January 2002

J. S. SINSHEIMER
Affiliation:
Departments of Human Genetics and Biomathematics, The University of California, Los Angeles, USA
C. A. MCKENZIE
Affiliation:
Tropical Metabolism Research Unit, University of the West Indies, Kingston, Jamaica
B. KEAVNEY
Affiliation:
School of Clinical Medical Sciences, The Medical School, University of Newcastle, Newcastle, UK
K. LANGE
Affiliation:
Departments of Human Genetics and Biomathematics, The University of California, Los Angeles, USA
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Abstract

The gamete competition model is a likelihood version of the transmission disequilibrium test (TDT) that is inspired by conditional logistic regression and the Bradley–Terry ranking procedure. In family-based association studies, both the TDT and the gamete competition model apply directly to data on a single nucleotide polymorphism (SNP). Because any given SNP has limited polymorphism, it is tempting to collect several SNPs within a gene into a single super marker whose alleles are haplotypes. Unfortunately, this tactic wreaks havoc with the traditional TDT, which requires codominant markers (Spielman et al. 1993; Terwilliger & Ott, 1992). Eliminating phase ambiguities by assigning haplotypes to individuals before conducting the TDT may give misleading results because only the most probable haplotypes are then considered. Because pedigree implementations of the gamete competition model can accommodate dominant as well as codominant markers, they circumvent the phase problem by including all possible phases weighted by their estimated frequencies.

Type
Review Article
Copyright
University College London 2001

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