Details

Autor(en) / Beteiligte

• Chadwick, B P
• Leyne, M
• Gill, S
• Liebert, C B
• Mull, J
• Mezey, E
• Robbins, C M
• Pinkett, H W
• Makalowska, I
• Maayan, C
• Blumenfeld, A
• Axelrod, F B
• Brownstein, M
• Gusella, J F
• Slaugenhaupt, S A

Titel

Cloning, mapping, and expression of a novel brain-specific transcript in the familial dysautonomia candidate region on chromosome 9q31

Ist Teil von

• Mammalian genome, 2000-01, Vol.11 (1), p.81-83

Ort / Verlag

United States: Springer Nature B.V

Erscheinungsjahr

2000

Link zum Volltext

Quelle

SpringerLINK Contemporary (Konsortium Baden-Württemberg)

Beschreibungen/Notizen

• Familial Dysautonomia (FD) or Hereditary Sensory and Autonomic Neuropathy Type-III (HSANIII) is an autosomal recessive disorder affecting the development and survival of sensory, sympathetic, and some parasympathetic neurons with progressive neuronal degeneration thoughout life (Riley et al. 1949; Axelrod et al. 1974). The developmental loss of neuronal populations results in numerous clinical problems and a reduced quality of life for patients, ultimately leading to a premature death. One diagnostic feature of the disorder is an almost exclusive restriction to persons of Ashkenazi Jewish descent (Brunt and McKusick 1970). With a carrier frequency of 1 in 30 and a presentation of 1 in 3600 live births, FD is a common genetic disorder within this ethnic group with a frequency that is comparable to that of the more widely recognized recessive disorders cystic fibrosis and Tay-Sachs disease (Maayan et al. 1987). A genome-wide scan performed in our laboratory demonstrated linkage of FD to an 11-cM region of human Chromosome (Chr) 9q31-33 between the genetic markers D9S53 and D9S105 with a maximum lod score of 21.1 (Blumenfeld et al. 1993). Analysis of linked markers within the candidate region showed strong linkage disequilibrium demonstrating a founder effect. Recently haplotype analysis has narrowed the candidate region to less than 0.5 cM (Blumenfeld et al. 1999) and suggests that greater than 99% of all FD chromosomes carry the same mutation. Here we describe the cloning, mapping, and expression of a novel, brain-specific transcript CG-6 (C9ORF4), from the FD candidate region. Because of the lack of a cellular phenotype, a positional cloning approach was adopted to identify the FD gene. We have constructed a complete physical map of the candidate region that consists of BACs and cosmids (Slaugenhaupt et al., unpublished data), and have used cDNA selection and exon trapping to identify transcribed sequences.