An extension of the admixture test for the study of genetic heterogeneity in hereditary multiple exostoses |
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Authors: | Laurence Legeai-Mallet Patricia Margaritte-Jeannin Mohamed Lemdani M Le Merrer Henry Plauchu Pierre Maroteaux A Munnich Françoise Clerget-Darpoux |
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Institution: | Département de Génétique et Unité de Recherches sur les Handicaps Génétiques de l’Enfant, INSERM U-393, H?pital des Enfants-Malades, 149 Rue de Sèvres, F-75743 Paris Cedex 15, France, FR Unité de Recherches de Génétique Epidémiologique INSERM U-155, Chateau de Longchamp, F-75016 Paris, France, FR Laboratoire de Biomathématiques, Faculté de Pharmacie, B.P. 83, F-59006 Lille, France, FR H?pital Edouard Herriot, 5 Place d’Arsonval, F-69437 Lyon Cedex 03, France, FR
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Abstract: | Hereditary multiple exostoses (EXT) is an autosomal dominant disorder characterized by the presence of multiple cartilage-capped
exostoses in the juxta-epiphyseal regions of the long bones. EXT is heterogeneous with at least three different locations
currently having been identified on chromosomes 8, 11 and 19. We have tested a series of 29 EXT families for possible linkage
to the three disease loci and estimated the probability of linkage of the disease to each locus in our series, by using an
extension of the admixture test, which makes modelling of heterogeneous monogenic disease feasible. The maximum likelihood
was obtained for proportions of 44%, 28% and 28% of families being linked to chromosome 8, 11 and 19, respectively. The a
posteriori probability of linkage of the disease to EXT1, EXT2 and EXT3 was greater than 80% for 8/29, 5/29 and 3/29 families,
respectively, and did not give evidence of a fourth locus for the disease. The present approach can be generalized to the
investigation of genetic heterogeneity in other monogenic diseases, as it simultaneously estimates the location of each disease
gene and the proportion of families linked to each locus.
Received: 28 May 1996 / Revised: 7 October 1996 |
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