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Mapping quantitative effects of oligogenes by allelic association

Published online by Cambridge University Press:  31 July 2002

W. ZHANG
Affiliation:
Human Genetics Division, Duthie Building (MP 808), Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK
A. COLLINS
Affiliation:
Human Genetics Division, Duthie Building (MP 808), Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK
G. R. ABECASIS
Affiliation:
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK
L. R. CARDON
Affiliation:
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK
N. E. MORTON
Affiliation:
Human Genetics Division, Duthie Building (MP 808), Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK
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Abstract

Regression analysis of a quantitative trait as a function of a single diallelic polymorphism has been extended to allelic association by composite likelihood under the Malecot model for multiple markers. We applied the method to 10 single nucleotide polymorphisms (SNPs) spanning 27 kb of the angiotensin-I converting enzyme (ACE) gene in British families, localising a causal SNP between G2530A and 4656(CT)3/2 in the 3′ region, at a distance of 21.6±0.9 kb from the most proximal SNP T-5491C. Neither they nor the I/D polymorphism is causal. To clarify genetic parameters we applied combined segregation, linkage and association analysis. Stronger evidence for the 3′ region was obtained, with significant evidence of a lesser 5′ effect as reported in French and Nigerian families. However, rigorous confirmation requires that the causal SNPs be identified. Both Malecot and parametric analysis appear to have high power by comparison with alternative methods for localizing oligogenes and their causal polymorphisms.

Type
Research Article
Copyright
University College London 2002

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