ATM mutations on distinct SNP and STR haplotypes in ataxia-telangiectasia patients of differing ethnicities reveal ancestral founder effects

Hum Mutat. 2003 Jan;21(1):80-5. doi: 10.1002/humu.10156.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Ataxia Telangiectasia / ethnology*
  • Ataxia Telangiectasia / genetics*
  • Ataxia Telangiectasia Mutated Proteins
  • Cell Cycle Proteins
  • DNA Mutational Analysis / methods
  • DNA-Binding Proteins
  • Founder Effect
  • Haplotypes
  • Humans
  • Molecular Sequence Data
  • Mutation
  • Polymorphism, Single Nucleotide*
  • Polymorphism, Single-Stranded Conformational
  • Protein Serine-Threonine Kinases / genetics*
  • Tandem Repeat Sequences*
  • Tumor Suppressor Proteins


  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Tumor Suppressor Proteins
  • ATM protein, human
  • Ataxia Telangiectasia Mutated Proteins
  • Protein Serine-Threonine Kinases

Associated data

  • GENBANK/U82828
  • OMIM/208900