Abstract
The objective of this study was to identify novel causal genes involved in the pathogenesis of Kashin-Beck disease (KBD). A representative grade III KBD sib pair with serious skeletal growth and development failure was subjected to exome sequencing using the Illumina Hiseq2000 platform. The detected gene mutations were then filtered against the data of 1000 Genome Project, dbSNP database, and BGI inhouse database, and replicated by a genome-wide association study (GWAS) of KBD. Ninety grade II or III KBD patients with extreme KBD phenotypes and 1627 healthy controls were enrolled in the GWAS. Affymetrix Genome-Wide Human SNP Array 6.0 was applied for genotyping. PLINK software was used for association analysis. We identified a novel 106T>C at the 3′UTR of the FGF12 gene, which has not been reported by now. Sequence alignment observed high conversation at the mutated 3′UTR+106T>C locus across various vertebrates. In the GWAS of KBD, we detected nine SNPs of the FGF12 gene showing association evidence (P value < 0.05) with KBD. The most significant association signal was observed at rs1847340 (P value = 1.90 × 10−5). This study suggests that FGF12 was a susceptibility gene of KBD. Our results provide novel clues for revealing the pathogenesis of KBD and the biological function of FGF12.
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Acknowledgments
The study was supported by National Natural Scientific Fund of China (81472925), the National High Technology Research and Development Program of China-863 Program (no. 2012AA02A201), Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry, Shenzhen Municipal Science and Technology Innovation Council (CXZZ20140904154910774), and The Science and Technology Research and Development Program of Shaanxi Province of China (2013KJXX-51).
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The authors declare that they have no competing interests.
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Feng Zhang and Lanlan Dai contributed equally to this work.
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Zhang, F., Dai, L., Lin, W. et al. Exome sequencing identified FGF12 as a novel candidate gene for Kashin-Beck disease. Funct Integr Genomics 16, 13–17 (2016). https://doi.org/10.1007/s10142-015-0462-z
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DOI: https://doi.org/10.1007/s10142-015-0462-z