Genetic Haplotyping of Ataxia-telangiectasia Families Localizes the Major Gene to an ∼ 850 kb Region on Chromosome 11q23.1

Abstract

The genotyping data given localize the major A-T gene to an approximately 850 kb region. They also localize the group A A-T gene (ATA) to a region that contains the approximately 850 kb region. They are compatible with linking A-TFresno to 11q22-23. NBS-V2 does not link to this region. Four non-linking families contain only single affecteds, suggesting that these may be spontaneous mutations rather than evidence for an A-T gene outside the 11q22-23 region. Finally, two other non-linking families contain recombinant haplotypes that are compatible with a second A-T gene at 11q22-23, slightly distal to the approximately 850 kb region. However, convincing evidence for a second gene is still lacking.

Identical mutation in 55% of the ATM alleles in 11 Norwegian AT families: evidence for a founder effect

“…This is one of the six non-linked families in the 176 AT families used positionally to clone the ATM gene. 16,17 .…”

“…12 The ATM gene was cloned in 1995, 13,14 following a seven-year positional cloning study by an international consortium. [15][16][17] It spans approximately 150 kb genomic DNA and contains 66 exons including alternative splicing variants. The major ATM transcript is 12 kb and the protein is correspondingly large (approx.…”

Autosomal recessive cerebellar ataxias

“…However, linkage studies showed only one locus on chromosome 11q23 accounting for the disease in different populations [49,50]. Mutation analysis of the ATM gene has confirmed the genetic homogeneity of A-T.…”

High Frequency and Error-prone DNA Recombination in Ataxia Telangiectasia Cell Lines

“…Following localization of the A-T gene to 850 kb on the long arm of chromosome 11 (4,5), it now appears to have been cloned (6). The surprising result is that one gene is mutated in all the complementation groups, which makes the original observations of complementation groups difficult to rationalize.…”