KCNQ4: a gene for age-related hearing impairment?
| Autor: | Vedat Topsakal, W. Laureys, Nele Lemkens, G. Van Camp, Erik Fransen, N. Nelissen, P. Van de Heyning, Thomas F. Wienker, E. Van Eyken, Ann Vandevelde, L. Van Laer |
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| Rok vydání: | 2006 |
| Předmět: |
Adult
Male Linkage disequilibrium Genotype Population DNA Mutational Analysis Quantitative Trait Loci Presbycusis Single-nucleotide polymorphism Quantitative trait locus Biology Polymorphism Single Nucleotide Linkage Disequilibrium Gene Frequency Genetics medicine SNP Humans Genetic Predisposition to Disease education Hearing Loss Gene Genetics (clinical) Aged 80 and over education.field_of_study Analysis of Variance KCNQ Potassium Channels Models Genetic Age Factors Middle Aged medicine.disease Haplotypes Female KCNQ4 |
| Zdroj: | Human mutation |
| ISSN: | 1098-1004 1059-7794 |
| Popis: | Age-related hearing impairment (ARHI) is the most common sensory impairment among the elderly. It is a complex disorder influenced by genetic as well as environmental factors. SNPs in a candidate susceptibility gene, KCNQ4, were examined in two independent Caucasian populations. Two quantitative trait locus (QTL) values were investigated: Zhigh and Zlow, a measure of high and respectively low frequency hearing loss. In the first population, the statistical analysis of 23 genotyped SNPs spread across KCNQ4 resulted in significant p-values for two SNPs for Zhigh—SNP9 (NT_004511:g.11244177A>T) and SNP15 (NT_004511:g.11257005C>T; NP_004691:p.Ala259Ala), and one SNP for Zlow—SNP12 (NT_004511:g.11249550A>T). The linkage disequilibrium (LD) structure of KCNQ4 was subsequently determined in a 34-kb region surrounding the significant SNPs, resulting in three LD-blocks. LD-block 1 contains SNP9 and covers an area of 5 kb, LD-block 2 measures 5 kb and surrounds SNP13 (NT_004511:g.11253513A>G) to SNP18 (NT_004511:g.11257509G>A; NP_004691:p.Thr293Thr), and LD-block 3 spans 7 kb. Five tag-SNPs of block 1 and 2, and 2 extra SNPs were subsequently genotyped in the second population. Again, several SNPs were positively associated with ARHI: one SNP (SNP18) for the high frequencies and three SNPs (SNP9, SNP12, and SNP18) for the low frequencies, although only a single SNP (SNP12) resulted in significant p-values in both populations. Nevertheless, the associated SNPs of both populations were all located in the same 13-kb region in the middle of the KCNQ4 gene. Hum Mutat 27(10), 1007–1016, 2006. © 2006 Wiley-Liss, Inc. |
| Databáze: | OpenAIRE |
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