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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Clouston hidrotic ectodermal dysplasia ( HED): genetic homogeneity, presence of a founder effect in the French Canadian population and fine genetic mapping.

HED is an autosomal dominant skin disorder that is particularly common in the French Canadian population of south-west Quebec. We previously mapped the HED gene to the pericentromeric region of chromosome 13q using linkage analysis in eight French Canadian families. In this study, we extend our genetic analysis to include a multiethnic group of 29 families with 10 polymorphic markers spanning 5.1 cM in the candidate region. Two-point linkage analysis strongly suggests absence of genetic heterogeneity in HED in four families of French, Spanish, African and Malaysian origins. Multipoint linkage analysis in all 29 families generated a peak lod score of 53.5 at D13S1835 with a 1 lod unit support interval spanning 1.8 cM. Recombination mapping placed the HED gene in a 2.4 cM region flanked by D13S1828 proximally and D13S1830 distally. We next show evidence for a strong founder effect in families of French Canadian origin thereby representing the first example of a founder disease in the south-west part of the province of Quebec. Significant association was found between HED in these families and all markers analysed (Fisher's exact test, P < 0.001). Complete allelic association was detected at D13S1828, D13S1827, D13S1835, D13S141 and D13S175 (P(excess) = 1) spanning 1.3 cM. A major haplotype including all 10 associated alleles was present on 65% of affected chromosomes. This haplotype most likely represents the founder haplotype that introduced the HED mutation into the French Canadian population. Luria-Delbrück equations and multipoint likelihood linkage disequilibrium analysis positioned the gene at the D13S1828 locus (likely range estimate: 1.75 cM) and 0.58 cM telomeric to this marker (support interval: 3.27 cM) respectively.[1]


  1. Clouston hidrotic ectodermal dysplasia (HED): genetic homogeneity, presence of a founder effect in the French Canadian population and fine genetic mapping. Kibar, Z., Dubé, M.P., Powell, J., McCuaïg, C., Hayflick, S.J., Zonana, J., Hovnanian, A., Radhakrishna, U., Antonarakis, S.E., Benohanian, A., Sheeran, A.D., Stephan, M.L., Gosselin, R., Kelsell, D.P., Christianson, A.L., Fraser, F.C., Der Kaloustian, V.M., Rouleau, G.A. Eur. J. Hum. Genet. (2000) [Pubmed]
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