Whole-exome sequencing to decipher the genetic heterogeneity of hearing loss in a Chinese family with deaf by deaf mating

Jie Qing, Denise Yan, Yuan Zhou, Qiong Liu, Weijing Wu, Zian Xiao, Yuyuan Liu, Jia Liu, Lilin Du, Dinghua Xie, Xue Z Liu

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Inherited deafness has been shown to have high genetic heterogeneity. For many decades, linkage analysis and candidate gene approaches have been the main tools to elucidate the genetics of hearing loss. However, this associated study design is costly, time-consuming, and unsuitable for small families. This is mainly due to the inadequate numbers of available affected individuals, locus heterogeneity, and assortative mating. Exome sequencing has now become technically feasible and a cost-effective method for detection of disease variants underlying Mendelian disorders due to the recent advances in next-generation sequencing (NGS) technologies. In the present study, we have combined both the Deafness Gene Mutation Detection Array and exome sequencing to identify deafness causative variants in a large Chinese composite family with deaf by deaf mating. The simultaneous screening of the 9 common deafness mutations using the allele-specific PCR based universal array, resulted in the identification of the 1555A≥G in the mitochondrial DNA (mtDNA) 12S rRNA in affected individuals in one branch of the family. We then subjected the mutation-negative cases to exome sequencing and identified novel causative variants in the MYH14 and WFS1 genes. This report confirms the effective use of a NGS technique to detect pathogenic mutations in affected individuals who were not candidates for classical genetic studies.

Original languageEnglish
Article numbere109178
JournalPLoS One
Volume9
Issue number10
DOIs
StatePublished - Oct 7 2014

Fingerprint

Exome
deafness
Genetic Heterogeneity
Audition
hearing
Deafness
Hearing Loss
Genes
mutation
Mutation
Mitochondrial DNA
disease detection
genes
assortative mating
Screening
Genetic Association Studies
linkage (genetics)
mitochondrial DNA
experimental design
Alleles

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Whole-exome sequencing to decipher the genetic heterogeneity of hearing loss in a Chinese family with deaf by deaf mating. / Qing, Jie; Yan, Denise; Zhou, Yuan; Liu, Qiong; Wu, Weijing; Xiao, Zian; Liu, Yuyuan; Liu, Jia; Du, Lilin; Xie, Dinghua; Liu, Xue Z.

In: PLoS One, Vol. 9, No. 10, e109178, 07.10.2014.

Research output: Contribution to journalArticle

Qing, Jie ; Yan, Denise ; Zhou, Yuan ; Liu, Qiong ; Wu, Weijing ; Xiao, Zian ; Liu, Yuyuan ; Liu, Jia ; Du, Lilin ; Xie, Dinghua ; Liu, Xue Z. / Whole-exome sequencing to decipher the genetic heterogeneity of hearing loss in a Chinese family with deaf by deaf mating. In: PLoS One. 2014 ; Vol. 9, No. 10.
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