Fine-scale mapping using Hardy-Weinberg disequilibrium.
Ann Hum Genet
; 65(Pt 2): 207-19, 2001 Mar.
Article
en En
| MEDLINE
| ID: mdl-11427179
ABSTRACT
Hardy-Weinberg disequilibrium (HWD) among affected individuals has recently been proposed for fine-scale mapping of disease susceptibility genes. We investigate the statistical properties of several available HWD measures and develop a new HWD measure J for fine-scale mapping. It is shown both theoretically and through simulations that the available HWD measures depend not only on the genetic distance between the marker locus of interest and the disease susceptibility locus, but also on the allele frequencies at the marker locus. On the contrary, the new measure is not affected by the allele frequencies at the marker locus under the following assumptions (a) there is initial complete linkage disequilibrium between the marker and the disease loci, (b) there are no new mutations at the marker and the disease loci, and (c) the population under study is large. We develop a novel method to estimate the location of the disease susceptibility gene based on the HWD measure J. The estimator is robust to low mutation rates at the marker and the disease loci. We compare the standard error of the estimated disease gene loci using P excess for case-control studies with the standard error using J for case-only studies under various disease models. The newly developed method is successfully applied to a data set on hereditary haemochromatosis (HH).
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Desequilibrio de Ligamiento
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Mapeo Cromosómico
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Predisposición Genética a la Enfermedad
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Hemocromatosis
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Modelos Genéticos
Tipo de estudio:
Observational_studies
Límite:
Humans
Idioma:
En
Revista:
Ann Hum Genet
Año:
2001
Tipo del documento:
Article
Pais de publicación:
ENGLAND
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ESCOCIA
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GB
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GREAT BRITAIN
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INGLATERRA
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REINO UNIDO
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SCOTLAND
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UK
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UNITED KINGDOM