Bloom syndrome: An analysis of consanguineous families assigns the locus mutated to chromosome band 15q26.1

James German, Anne Marie Roe, Mark F. Leppert, Nathan A. Ellis

Research output: Contribution to journalArticle

66 Scopus citations

Abstract

By the principle of identity by descent, parental consanguinity in individuals with rare recessively transmitted disorders dictates homozygosity not just at the mutated disease-associated locus but also at sequences that flank that locus closely. In 25 of 26 individuals with Bloom syndrome examined whose parents were related, a polymorphic tetranucleotide repeat in an intron of the protooncogene FES was homozygous, far more often than expected (P < 0.0001 by χ2). Therefore, BLM, the gene that when mutated gives rise to Bloom syndrome, is tightly linked to FES, a gene whose chromosome position is known to be 15q26.1. This successful approach to the assignment of the Bloom syndrome locus to one short segment of the human genome simultaneously (i) demonstrates the power of homozygosity mapping and (ii) becomes the first step in a 'reverse' genetics definition of the primary defect in Bloom syndrome.

Original languageEnglish (US)
Pages (from-to)6669-6673
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume91
Issue number14
DOIs
StatePublished - Jul 5 1994
Externally publishedYes

Keywords

  • chromosome- breakage syndrome
  • genomic instability
  • homozygosity mapping
  • linkage analysis

ASJC Scopus subject areas

  • General

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