Severe combined immunodeficiency disease (SCID) consists of a group of heterogeneous genetic disorders. The most severe phenotype, T2B2 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 T2B2 SCID among Athabascan-speaking Native Americans (A-SCID). To
localize the A-SCID gene, we conducted a genomewide search, using linkage analysis of ?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 chromosome10p. 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 v 5 .00. Recombination events placed the gene in an interval of ?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 ?6.5 cM in the candidate region, suggesting a founder
effect with an ancestral mutation that occurred
sometime before 1300 A.D.