Molecular genetics of Bloom's syndrome

Nathan Ellis, James German

Research output: Contribution to journalArticle

135 Citations (Scopus)

Abstract

Mutation of the Bloom's syndrome (BS) gene, BLM, results in genomic instability. As the first step toward positional cloning of the gene, tight linkage of BLM and FES at 15q26.1 was detected by genotyping affected in families in which the parents are cousins, so-called homozygosity mapping. Linkage disequilibrium between BLM and FES was detected in Ashkenazi Jews with BS, confirming the linkage results and supporting the hypothesis that the increased frequency of the BS mutation in the Ashkenazim is due to founder effect. The mutated BLM gene is inherited identical by descent in BS persons whose parents are cousins or Ashkenazi Jewish; in persons whose parents do not share a common ancestor, BLM can be mutant at different positions within the gene. In such persons, crossing-over within BLM can occur to form a functionally wild-type gene capable of correcting the mutant phenotype of BS cells. In half the cases in which such somatic intragenic recombination had occurred, reduction to homozygosity was detectable distal to BLM but not proximal to it. We localized the cross-over points in corrected cells to a 250 kb genomic segment and isolated therefrom a 4437 bp cDNA that encodes a 1417 amino acid protein homologous to the RecQ subfamily of DExH box-containing DNA and RNA helicases. The identification of BLM as a putative DNA helicase provides a new and powerful tool to investigate the primary defect in BS and the function of the BLM gene product in maintaining the integrity of the genome.

Original languageEnglish (US)
Pages (from-to)1457-1463
Number of pages7
JournalHuman Molecular Genetics
Volume5
Issue numberREVIEW
StatePublished - 1996
Externally publishedYes

Fingerprint

Bloom Syndrome
Molecular Biology
DNA Helicases
Genes
Parents
RNA Helicases
Founder Effect
Jews
Mutation
Gene Order
Genomic Instability
Linkage Disequilibrium
Genetic Recombination
Organism Cloning
Complementary DNA
Genome
Phenotype
Amino Acids

ASJC Scopus subject areas

  • Genetics

Cite this

Ellis, N., & German, J. (1996). Molecular genetics of Bloom's syndrome. Human Molecular Genetics, 5(REVIEW), 1457-1463.

Molecular genetics of Bloom's syndrome. / Ellis, Nathan; German, James.

In: Human Molecular Genetics, Vol. 5, No. REVIEW, 1996, p. 1457-1463.

Research output: Contribution to journalArticle

Ellis, N & German, J 1996, 'Molecular genetics of Bloom's syndrome', Human Molecular Genetics, vol. 5, no. REVIEW, pp. 1457-1463.
Ellis, Nathan ; German, James. / Molecular genetics of Bloom's syndrome. In: Human Molecular Genetics. 1996 ; Vol. 5, No. REVIEW. pp. 1457-1463.
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