Evidence for linkage between Wilson disease and esterase D in three kindreds: detection of linkage for an autosomal recessive disorder by the family study method.
Wilson disease (WD) is an inherited disorder of copper metabolism that affects the brain, liver, and other organs. Our group recently reported close linkage between the locus for WD and a polymorphic red cell enzyme, esterase D (EsD), in a large inbred Israeli-Arab lineage. We have subsequently studied two unrelated Druze kindreds in order to confirm this linkage and more precisely define the distance between the two loci. The maximum likelihood estimate of recombination was determined to be zero with lod scores of 1.48 and 1.06 in each Druze family, respectively. The combined maximum lod score based on pooled results from the Israeli-Arab and Druze kindreds is 5.49 at theta = 0.03. WD is one of a few autosomal recessive disorders that has been mapped by classical family study methods. In this paper, the merits for using large, inbred families in linkage studies of rare recessive disorders are discussed. Major considerations for pedigree selection are size and number of constituent nuclear families, number and distribution of affected individuals, and pedigree structure that may provide information for determination of phase between the disease and marker loci.
Bonné-Tamir
B
B
Farrer
L A
LA
Frydman
M
M
Kanaaneh
H
H
D000328:Adult; D043182:Carboxylesterase; D002265:Carboxylic Ester Hydrolases / Q000235:genetics*; D002648:Child; D002874:Chromosome Mapping; D002901:Chromosomes, Human, 13-15; D003241:Consanguinity; D005006:Ethnicity; D005260:Female; D005808:Genes, Recessive; D008040:Genetic Linkage; D005819:Genetic Markers; D006527:Hepatolenticular Degeneration / Q000235:genetics*; D006801:Humans; D007557:Israel; D008126:Lod Score; D008297:Male; D010375:Pedigree; D011110:Polymorphism, Genetic; D011995:Recombination, Genetic
D005819:Genetic Markers; D002265:Carboxylic Ester Hydrolases; D043182:Carboxylesterase; C020118:ESD protein, human