Journal article
Genomic structures of SCN2A and SCN3A – candidate genes for deafness at the DFNA16 locus
Gene, Vol.264(1), pp.113-122
2001
DOI: 10.1016/S0378-1119(00)00594-1
PMID: 11245985
Abstract
DFNA16 is a form of autosomal dominant non-syndromic hearing loss (ADNSHL) characterized by fluctuating progressive hearing impairment. Earlier, we mapped the deafness-causing gene to chromosome 2q23-24.3. In this paper, we describe fine mapping results using additional markers tightly linked to the
DFNA16 candidate region. Critical recombinants at markers D2S354 and D2S124 define a 3.5-cM interval that contains the
DFNA16 gene. Positional candidate genes include two members of the voltage-gated sodium channel family, the type 2 α subunit (
SCN2A) and the type 3 α subunit (
SCN3A). After showing that
SCN2A is expressed in human fetal cochlea, we determined its genomic structure to facilitate mutation screening in our
DFNA16 kindred. We also determined the genomic structure of
SCN3A. These two genes are oriented head-to-head, with their 5′ ends separated by approximately 40 kb; their homology is 82% at the nucleotide level, and 85% for identities and 90% for positives at the amino acid level. They share similar genomic structures and have alternative splice isoforms that are developmentally regulated and highly conserved between species. Although no
DFNA16-causing mutations were found in either gene, haplotype analysis with polymorphic markers in
SCN2A introns further narrowed the candidate gene interval to the region flanked by D2S354 and STS SHGC-82894.
Details
- Title: Subtitle
- Genomic structures of SCN2A and SCN3A – candidate genes for deafness at the DFNA16 locus
- Creators
- Norio Kasai - Department of Otolaryngology, Okayama University Medical School, Okayama, 700-8558, JapanKunihiro Fukushima - Department of Otolaryngology, Okayama University Medical School, Okayama, 700-8558, JapanYasuyoshi Ueki - Molecular Biology and Biochemistry, Okayama University Medical School, Okayama, 700-8558, JapanSai Prasad - Department of Otolaryngology, University of Iowa, Iowa City, IA 52242, USAJennifer Nosakowski - Department of Otolaryngology, University of Iowa, Iowa City, IA 52242, USAKen-ichi Sugata - Department of Otolaryngology, Okayama University Medical School, Okayama, 700-8558, JapanAkemi Sugata - Department of Otolaryngology, Okayama University Medical School, Okayama, 700-8558, JapanKazunori Nishizaki - Department of Otolaryngology, Okayama University Medical School, Okayama, 700-8558, JapanNicole C Meyer - Department of Otolaryngology, University of Iowa, Iowa City, IA 52242, USARichard J.H Smith - Department of Otolaryngology, University of Iowa, Iowa City, IA 52242, USA
- Resource Type
- Journal article
- Publication Details
- Gene, Vol.264(1), pp.113-122
- DOI
- 10.1016/S0378-1119(00)00594-1
- PMID
- 11245985
- NLM abbreviation
- Gene
- ISSN
- 0378-1119
- eISSN
- 1879-0038
- Publisher
- Elsevier B.V
- Grant note
- DOI: 10.13039/501100003478, name: Ministry of Health, Labour and Welfare; DOI: 10.13039/501100003606, name: Korea Foundation, award: RO1-DC03544; DOI: 10.13039/501100001700, name: Ministry of Education, Culture, Sports, Science and Technology
- Language
- English
- Date published
- 2001
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Molecular Physiology and Biophysics; Anatomy and Cell Biology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Otolaryngology; Internal Medicine
- Record Identifier
- 9984007197302771
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