Function-driven discovery of disease genes in zebrafish using an integrated genomics big data resource

Hongseok Shim, Ji Hyun Kim, Chan Yeong Kim, Sohyun Hwang, Hyojin Kim, Sunmo Yang, Ji Eun Lee, In suk Lee

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Whole exome sequencing (WES) accelerates disease gene discovery using rare genetic variants, but further statistical and functional evidence is required to avoid false-discovery. To complement variant-driven disease gene discovery, here we present function-driven disease gene discovery in zebrafish (Danio rerio), a promising human disease model owing to its high anatomical and genomic similarity to humans. To facilitate zebrafish-based function-driven disease gene discovery, we developed a genome-scale co-functional network of zebrafish genes, DanioNet (www.inetbio.org/danionet), which was constructed by Bayesian integration of genomics big data. Rigorous statistical assessment confirmed the high prediction capacity of DanioNet for a wide variety of human diseases. To demonstrate the feasibility of the function-driven disease gene discovery using DanioNet, we predicted genes for ciliopathies and performed experimental validation for eight candidate genes. We also validated the existence of heterozygous rare variants in the candidate genes of individuals with ciliopathies yet not in controls derived from the UK10K consortium, suggesting that these variants are potentially involved in enhancing the risk of ciliopathies. These results showed that an integrated genomics big data for a model animal of diseases can expand our opportunity for harnessing WES data in disease gene discovery.

Original languageEnglish
Pages (from-to)9611-9623
Number of pages13
JournalNucleic Acids Research
Volume44
Issue number20
DOIs
Publication statusPublished - 2016 Jan 1

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Genetic Association Studies
Zebrafish
Genomics
Exome
Genes
Animal Disease Models
Gene Regulatory Networks
Genome
Ciliopathies

All Science Journal Classification (ASJC) codes

  • Genetics

Cite this

Shim, Hongseok ; Kim, Ji Hyun ; Kim, Chan Yeong ; Hwang, Sohyun ; Kim, Hyojin ; Yang, Sunmo ; Lee, Ji Eun ; Lee, In suk. / Function-driven discovery of disease genes in zebrafish using an integrated genomics big data resource. In: Nucleic Acids Research. 2016 ; Vol. 44, No. 20. pp. 9611-9623.
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Function-driven discovery of disease genes in zebrafish using an integrated genomics big data resource. / Shim, Hongseok; Kim, Ji Hyun; Kim, Chan Yeong; Hwang, Sohyun; Kim, Hyojin; Yang, Sunmo; Lee, Ji Eun; Lee, In suk.

In: Nucleic Acids Research, Vol. 44, No. 20, 01.01.2016, p. 9611-9623.

Research output: Contribution to journalArticle

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