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ATM mutations on distinct SNP and STR haplotypes in ataxia‐telangiectasia patients of differing ethnicities reveal ancestral founder effects
Author(s) -
Campbell Catarina,
Mitui Midori,
Eng Laura,
Coutinho Gabriela,
Thorstenson Yvonne,
Gatti Richard A.
Publication year - 2003
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.10156
Subject(s) - haplotype , genetics , biology , snp , ataxia telangiectasia , mutation , founder effect , single nucleotide polymorphism , gene , genotype , dna , dna damage
Due to the large size (150 kb) of the ataxia‐telangiectasia mutated (ATM) gene and the existence of over 400 mutations, identifying mutations in patients with ataxia‐telangiectasia (A‐T) is labor intensive. We compared the SNP and STR haplotypes of A‐T patients from varying ethnicities who were carrying common ATM mutations. We used SSCP to determine SNP haplotypes. To our surprise, all of the most common ATM mutations in our large multiethnic cohort were associated with specific SNP haplotypes, whereas the STR haplotypes varied, suggesting that ATM mutations predated STR haplotypes but not SNP haplotypes. We conclude that these frequently observed ATM mutations are not hot spots, but have occurred only once and spread with time to different ethnic populations. More generally, a combination of SNP and STR haplotyping could be used as a screening strategy for identifying mutations in other large genes by first determining the ancestral SNP and STR haplotypes in order to identify specific founder mutations. We estimate this approach will identify approximately 30% of mutations in A‐T patients across all ethnic groups. Hum Mutat 21:80–85, 2002. © 2002 Wiley‐Liss, Inc.