The gene for severe combined immunodeficiency disease in Athabascan-speaking Native Americans is located on chromosome 10p.
Severe combined immunodeficiency disease (SCID) consists of a group of heterogeneous genetic disorders. The most severe phenotype, T-B- SCID, is inherited as an autosomal recessive trait and is characterized by a profound deficiency of both T cell and B cell immunity. There is a uniquely high frequency of T-B- SCID among Athabascan-speaking Native Americans (A-SCID). To localize the A-SCID gene, we conducted a genomewide search, using linkage analysis of approximately 300 microsatellite markers in 14 affected Athabascan-speaking Native American families. We obtained conclusive evidence for linkage of the A-SCID locus to markers on chromosome 10p. The maximum pairwise LOD scores 4.53 and 4.60 were obtained from two adjacent markers, D10S191 and D10S1653, respectively, at a recombination fraction of straight theta=.00. Recombination events placed the gene in an interval of approximately 6.5 cM flanked by D10S1664 and D10S674. Multipoint analysis positioned the gene for the A-SCID phenotype between D10S191 and D10S1653, with a peak LOD score of 5.10 at D10S191. Strong linkage disequilibrium was found in five linked markers spanning approximately 6.5 cM in the candidate region, suggesting a founder effect with an ancestral mutation that occurred sometime before 1300 A.D.
Li
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Department of Pediatrics, Bone Marrow Transplant Division, University of California, San Francisco, CA 94143-1278, USA.
Drayna
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D
Hu
D
D
Hayward
A
A
Gahagan
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S
Pabst
H
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Cowan
M J
MJ
D000483:Alleles; D002874:Chromosome Mapping; D002879:Chromosomes, Human, Pair 10; D005260:Female; D008040:Genetic Linkage; D005838:Genotype; D006801:Humans; D007198:Indians, North American / Q000235:genetics*; D008297:Male; D018895:Microsatellite Repeats; D010375:Pedigree; D010641:Phenotype; D016511:Severe Combined Immunodeficiency / Q000208:ethnology* / Q000235:genetics*