Refinement of the DFNA41 locus and candidate genes analysis

Denise Yan, Xiao Mei Ouyang, Xiaofeng Zhu, Li Lin Du, Zheng Yi Chen, Xue Z Liu

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

We previously mapped the 41 rst gene locus (DFNA41) for autosomal dominant hearing loss on chromosome 12q24-qter in a large multi-generational Chinese family. We determined that DFNA41 is located in a 15 cM region, proximal to the marker D12S1609. A maximum two point LOD score of 6.56 at θ=0.0 was obtained with marker D12S343. In the current study, screening of eight candidate genes within the DFNA41 interval did not reveal the mutation causing deafness in this family. Eight highly informative single nucleotide polymorphisms (SNPs) in the region of D12S343 were selected for linkage and association study. Because the pedigree studied here is a large family with many founders, we applied the transmission/disequilibrium (TDT) test. To account for the dependence of small families and the relatively small sample size, simulations were performed to obtain P-values. For three nearby SNPs spanning a 7 kb interval, we found significant evidence of linkage and association. The highest Z score of linkage and association of 3.6 (P < 0.0001) was obtained for SNP rs1566667. Haplotype analysis revealed that affected individuals were heterozygous for one core SNP (rs1027560-rs1027557- rs1566667-rs1463865-rs2078105) CAGTC haplotype, confirming location and autosomal dominant inheritance of the DFNA41 locus. Examination of pairwise LD calculation identified a major haplotype block defined by the four most centromeric SNPs. This study represents a significant refinement of the DFNA41 locus and should facilitate positional cloning of the disease gene.

Original languageEnglish
Pages (from-to)516-522
Number of pages7
JournalJournal of Human Genetics
Volume50
Issue number10
DOIs
StatePublished - Oct 1 2005

Fingerprint

Genetic Association Studies
Single Nucleotide Polymorphism
Haplotypes
Genes
Deafness
Pedigree
Hearing Loss
Sample Size
Organism Cloning
Chromosomes
Autosomal Dominant 41 Deafness
Mutation

Keywords

  • Autosomal dominant
  • Linkage and association analysis
  • Non-syndromic hearing loss
  • Single nucleotide polymorphism

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Refinement of the DFNA41 locus and candidate genes analysis. / Yan, Denise; Ouyang, Xiao Mei; Zhu, Xiaofeng; Du, Li Lin; Chen, Zheng Yi; Liu, Xue Z.

In: Journal of Human Genetics, Vol. 50, No. 10, 01.10.2005, p. 516-522.

Research output: Contribution to journalArticle

Yan, Denise ; Ouyang, Xiao Mei ; Zhu, Xiaofeng ; Du, Li Lin ; Chen, Zheng Yi ; Liu, Xue Z. / Refinement of the DFNA41 locus and candidate genes analysis. In: Journal of Human Genetics. 2005 ; Vol. 50, No. 10. pp. 516-522.
@article{4d88cf568cdf4a778c385fb2595d2544,
title = "Refinement of the DFNA41 locus and candidate genes analysis",
abstract = "We previously mapped the 41 rst gene locus (DFNA41) for autosomal dominant hearing loss on chromosome 12q24-qter in a large multi-generational Chinese family. We determined that DFNA41 is located in a 15 cM region, proximal to the marker D12S1609. A maximum two point LOD score of 6.56 at θ=0.0 was obtained with marker D12S343. In the current study, screening of eight candidate genes within the DFNA41 interval did not reveal the mutation causing deafness in this family. Eight highly informative single nucleotide polymorphisms (SNPs) in the region of D12S343 were selected for linkage and association study. Because the pedigree studied here is a large family with many founders, we applied the transmission/disequilibrium (TDT) test. To account for the dependence of small families and the relatively small sample size, simulations were performed to obtain P-values. For three nearby SNPs spanning a 7 kb interval, we found significant evidence of linkage and association. The highest Z score of linkage and association of 3.6 (P < 0.0001) was obtained for SNP rs1566667. Haplotype analysis revealed that affected individuals were heterozygous for one core SNP (rs1027560-rs1027557- rs1566667-rs1463865-rs2078105) CAGTC haplotype, confirming location and autosomal dominant inheritance of the DFNA41 locus. Examination of pairwise LD calculation identified a major haplotype block defined by the four most centromeric SNPs. This study represents a significant refinement of the DFNA41 locus and should facilitate positional cloning of the disease gene.",
keywords = "Autosomal dominant, Linkage and association analysis, Non-syndromic hearing loss, Single nucleotide polymorphism",
author = "Denise Yan and Ouyang, {Xiao Mei} and Xiaofeng Zhu and Du, {Li Lin} and Chen, {Zheng Yi} and Liu, {Xue Z}",
year = "2005",
month = "10",
day = "1",
doi = "10.1007/s10038-005-0286-0",
language = "English",
volume = "50",
pages = "516--522",
journal = "Journal of Human Genetics",
issn = "1434-5161",
publisher = "Nature Publishing Group",
number = "10",

}

TY - JOUR

T1 - Refinement of the DFNA41 locus and candidate genes analysis

AU - Yan, Denise

AU - Ouyang, Xiao Mei

AU - Zhu, Xiaofeng

AU - Du, Li Lin

AU - Chen, Zheng Yi

AU - Liu, Xue Z

PY - 2005/10/1

Y1 - 2005/10/1

N2 - We previously mapped the 41 rst gene locus (DFNA41) for autosomal dominant hearing loss on chromosome 12q24-qter in a large multi-generational Chinese family. We determined that DFNA41 is located in a 15 cM region, proximal to the marker D12S1609. A maximum two point LOD score of 6.56 at θ=0.0 was obtained with marker D12S343. In the current study, screening of eight candidate genes within the DFNA41 interval did not reveal the mutation causing deafness in this family. Eight highly informative single nucleotide polymorphisms (SNPs) in the region of D12S343 were selected for linkage and association study. Because the pedigree studied here is a large family with many founders, we applied the transmission/disequilibrium (TDT) test. To account for the dependence of small families and the relatively small sample size, simulations were performed to obtain P-values. For three nearby SNPs spanning a 7 kb interval, we found significant evidence of linkage and association. The highest Z score of linkage and association of 3.6 (P < 0.0001) was obtained for SNP rs1566667. Haplotype analysis revealed that affected individuals were heterozygous for one core SNP (rs1027560-rs1027557- rs1566667-rs1463865-rs2078105) CAGTC haplotype, confirming location and autosomal dominant inheritance of the DFNA41 locus. Examination of pairwise LD calculation identified a major haplotype block defined by the four most centromeric SNPs. This study represents a significant refinement of the DFNA41 locus and should facilitate positional cloning of the disease gene.

AB - We previously mapped the 41 rst gene locus (DFNA41) for autosomal dominant hearing loss on chromosome 12q24-qter in a large multi-generational Chinese family. We determined that DFNA41 is located in a 15 cM region, proximal to the marker D12S1609. A maximum two point LOD score of 6.56 at θ=0.0 was obtained with marker D12S343. In the current study, screening of eight candidate genes within the DFNA41 interval did not reveal the mutation causing deafness in this family. Eight highly informative single nucleotide polymorphisms (SNPs) in the region of D12S343 were selected for linkage and association study. Because the pedigree studied here is a large family with many founders, we applied the transmission/disequilibrium (TDT) test. To account for the dependence of small families and the relatively small sample size, simulations were performed to obtain P-values. For three nearby SNPs spanning a 7 kb interval, we found significant evidence of linkage and association. The highest Z score of linkage and association of 3.6 (P < 0.0001) was obtained for SNP rs1566667. Haplotype analysis revealed that affected individuals were heterozygous for one core SNP (rs1027560-rs1027557- rs1566667-rs1463865-rs2078105) CAGTC haplotype, confirming location and autosomal dominant inheritance of the DFNA41 locus. Examination of pairwise LD calculation identified a major haplotype block defined by the four most centromeric SNPs. This study represents a significant refinement of the DFNA41 locus and should facilitate positional cloning of the disease gene.

KW - Autosomal dominant

KW - Linkage and association analysis

KW - Non-syndromic hearing loss

KW - Single nucleotide polymorphism

UR - http://www.scopus.com/inward/record.url?scp=27644518633&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=27644518633&partnerID=8YFLogxK

U2 - 10.1007/s10038-005-0286-0

DO - 10.1007/s10038-005-0286-0

M3 - Article

VL - 50

SP - 516

EP - 522

JO - Journal of Human Genetics

JF - Journal of Human Genetics

SN - 1434-5161

IS - 10

ER -