Genetic mapping of the gene for Usher syndrome: linkage analysis in a large Samaritan kindred.
Usher syndrome is a group of autosomal recessive disorders associated with congenital sensorineural deafness and progressive visual loss due to retinitis pigmentosa. Sixteen members of the small inbred Samaritan isolate with autosomal recessive deafness were studied in 10 related sibships. DNA samples from 59 individuals including parents and affected and nonaffected sibs were typed for markers on chromosomes 1q and 11q for which linkage has recently been established for Usher syndrome types II and I. Statistically significant linkage was observed with four markers on 11q (D11S533, D11S527, OMP, and INT2) with a maximum six-point location score of 11.61 at the D11S533 locus. Analysis of haplotypes supports the notion that the mutation arose only once in an ancestral chromosome carrying a specific haplotype. The availability of markers closely linked to the disease locus allows indirect genotype analysis and identifies all carriers of the gene within the community. Furthermore, the detection of complete linkage disequilibrium between the D11S533 marker and the Usher gene suggests that these loci are either identical or adjacent and narrows the critical region to which physical mapping efforts are currently directed.
Bonné-Tamir
B
B
Department of Human Genetics, Sackler Faculty of Medicine, Ramat-Aviv, Israel.
Korostishevsky
M
M
Kalinsky
H
H
Seroussi
E
E
Beker
R
R
Weiss
S
S
Godel
V
V
D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1; D002880:Chromosomes, Human, Pair 11; D003241:Consanguinity; D005006:Ethnicity / Q000235:genetics; D005260:Female; D005808:Genes, Recessive; D008040:Genetic Linkage; D005819:Genetic Markers; D006239:Haplotypes; D006319:Hearing Loss, Sensorineural / Q000150:complications / Q000151:congenital / Q000235:genetics*; D006801:Humans; D007557:Israel; D008297:Male; D010375:Pedigree; D012174:Retinitis Pigmentosa / Q000150:complications / Q000235:genetics*; D013577:Syndrome
D005819:Genetic Markers