Connexin 26 35delG does not represent a mutational hotspot.

Hum Genet

Department of Microbiology and Molecular Genetics, Michigan State University, 5163 Biomedical and Physical Sciences Building, East Lansing, Michigan 48824-4320, USA.

Published: July 2003

AI Article Synopsis

  • Non-syndromic hearing impairment (NSHI) is primarily caused by mutations in the GJB2 gene, particularly the 35delG mutation, which is especially common among individuals of Mediterranean European descent.
  • Evidence suggests that the 35delG mutation is an old occurrence in a highly recombined chromosomal region, as it shows weak linkage with certain microsatellite markers, indicating substantial genetic recombination has occurred since its origin.
  • Analysis of single-nucleotide polymorphisms (SNPs) linked to the GJB2 gene revealed a similar rare polymorphism across diverse populations, supporting the idea that 35delG likely originated from a single mutational event affecting multiple regions.

Article Abstract

Non-syndromic hearing impairment (NSHI) is the most common form of deafness and presents with no other symptoms or sensory defects. Mutations in the gap junction gene GJB2 account for a high proportion of recessive NSHI. The GJB2 gene encodes connexin 26, which forms plasma membrane channels between cochlear cells. In Caucasian populations a single mutation, 35delG, accounts for most cases of NSHI. This mutation appears to be most prevalent in individuals of Mediterranean European descent, with carrier frequencies estimated as being as high as one in thirty. The 35delG region may be a mutational hotspot. The mutation arises from the deletion of a guanine from a six-guanine stretch and nearby microsatellite markers show little evidence for linkage disequilibrium. We believe that 35delG is an old mutation in a chromosomal region of high recombination. The genetic context of the 35delG mutation was examined to distinguish between an old or a recurring mutation. We identified two single-nucleotide polymorphisms (SNPs) immediately upstream of the first exon of GJB2. Polymerase chain reaction/restriction fragment length polymorphism analysis determined the SNP genotype of 35delG containing chromosomes from various populations, including Italy, Brazil, and North America. We found the same, relatively rare, polymorphism associated with the 35delG mutation in all populations studied. We have also examined microsatellite markers D13S175, which is 80 kb telomeric to GJB2, and D13S1316, which is 80 kb centromeric to GJB2. D13S175 appears to be in weak linkage disequilibrium with 35delG, while D13S1316 is less so. SNPs located between the 35delG mutation and the microsatellite markers show strong evidence of linkage disequilibrium. Taken together, these results indicate there has been substantial recombination near the 35delG mutation; however, we present evidence that the 35delG mutation arose in European and Middle Eastern populations from a single mutational event on a founder chromosome.

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00439-003-0944-2DOI Listing

Publication Analysis

Top Keywords

35delg mutation
24
microsatellite markers
12
linkage disequilibrium
12
mutation
10
35delg
10
mutational hotspot
8
populations single
8
evidence linkage
8
disequilibrium 35delg
8
gjb2
5

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!