caa a22 4500 397574509 CHVBK 20180308164851.0 cr unu---uuuuu 161202e199609 xx s 000 0 eng 10.1093/hmg/5.Supplement_1.1457 doi (NATIONALLICENCE)oxford-10.1093/hmg/5.Supplement_1.1457 Molecular genetics of Bloom's syndrome [Elektronische Daten] [Nathan A. Ellis, James German] 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. © 1996 Oxford University Press Ellis Nathan A. Laboratory of Human Genetics, New York Blood Center, 310 East 67th Street, New York, NY 10021, USA aut German James Laboratory of Human Genetics, New York Blood Center, 310 East 67th Street, New York, NY 10021, USA aut Human Molecular Genetics Oxford University Press 5/Supplement_1(1996-09), 1457-1463 0964-6906 5:Supplement_1<1457 1996 5 hmg https://doi.org/10.1093/hmg/5.Supplement_1.1457 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1093/hmg/5.Supplement_1.1457 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Ellis Nathan A. Laboratory of Human Genetics, New York Blood Center, 310 East 67th Street, New York, NY 10021, USA aut NATIONALLICENCE 700 1- German James Laboratory of Human Genetics, New York Blood Center, 310 East 67th Street, New York, NY 10021, USA aut NATIONALLICENCE 773 0- Human Molecular Genetics Oxford University Press 5/Supplement_1(1996-09), 1457-1463 0964-6906 5:Supplement_1<1457 1996 5 hmg Metadata rights reserved CC BY-NC-4.0 http://creativecommons.org/licenses/by-nc/4.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-oxford