Precise genetic mapping and haplotype analysis of the familial dysautonomia gene on human chromosome 9q31

Anat Blumenfeld, Susan A. Slaugenhaupt, Christopher B. Liebert, Violeta Temper, Channa Maayan, Sandra Gill, Diane E. Lucente, Maria Idelson, Kathy MacCrmack, Mary Anne Monahan, James Mull, Maire Leyne, Marc Mendillo, Taryn Schiripo, Esther Mishori, Xandra Breakefield, Felicia B. Axelrod, James F. Gusella*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

59 Scopus citations

Abstract

Familial dysautonomia (FD) is an autosomal recessive disorder characterized by developmental arrest in the sensory and autonomic nervous systems and by Ashkenazi Jewish ancestry. We previously had mapped the defective gene (DYS) to an 11-cM segment of chromosome 9q31-33, flanked by D9S53 and D9S105. By using 11 new polymorphic loci, we now have narrowed the location of DYS to <0.5 cM between the markers 43B1GAGT and 157A3. Two markers in this interval, 164D1 and D9S1677, show no recombination with the disease. Haplotype analysis confirmed this candidate region and revealed a major haplotype shared by 435 of 441 FD chromosomes, indicating a striking founder effect. Three other haplotypes, found on the remaining 6 FD chromosomes, might represent independent mutations. The frequency of the major FD haplotype in the Ashkenazim (5 in 324 control chromosomes) was consistent with the estimated DYS carrier frequency of 1 in 32, and none of the four haplotypes associated with FD was observed on 492 non-FD chromosomes from obligatory carriers. It is now possible to provide accurate genetic testing both for families with FD and for carriers, on the basis of close flanking markers and the capacity to identify >98% of FD chromosomes by their haplotype.

Original languageEnglish (US)
Pages (from-to)1110-1118
Number of pages9
JournalAmerican journal of human genetics
Volume64
Issue number4
DOIs
StatePublished - 1999

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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