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Genome-wide association study identifies COL2A1 locus involved in the hand development failure of Kashin-Beck disease.

ABSTRACT: Kashin-Beck disease (KBD) is a chronic osteochondropathy. The pathogenesis of growth and development failure of hand of KBD remains elusive now. In this study, we conducted a two-stage genome-wide association study (GWAS) of palmar length-width ratio (LWR) of KBD, totally including 493 study subjects. Affymetrix Genome Wide Human SNP Array 6.0 was applied for genome-wide SNP genotyping of 90?KBD patients. Association analysis was conducted by PLINK. Imputation analysis was performed by IMPUTE against the reference panel of the 1000 genome project. Two SNPs were selected for replication in an independent validation sample of 403?KBD patients. In the discovery GWAS, significant association was observed between palmar LWR and rs2071358 of COL2A1 gene (P value?=?4.68?×?10-8). In addition, GWAS detected suggestive association signal at rs4760608 of COL2A1 gene (P value?=?1.76?×?10-4). Imputation analysis of COL2A1 further identified 2 SNPs with association evidence for palmar LWR. Replication study observed significant association signals at both rs2071358 (P value?=?0.017) and rs4760608 (P value?=?0.002) of COL2A1 gene. Based on previous and our study results, we suggest that COL2A1 was a likely susceptibility gene involved in the hand development failure of KBD.

SUBMITTER: Hao J

PROVIDER: S-EPMC5216336 | biostudies-other | 2017 Jan

REPOSITORIES: biostudies-other

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Genome-wide association study identifies COL2A1 locus involved in the hand development failure of Kashin-Beck disease.

Hao Jingcan J Wang Wenyu W Wen Yan Y Xiao Xiao X He Awen A Wu Cuiyan C Wang Sen S Guo Xiong X Zhang Feng F

Scientific reports 20170106

Kashin-Beck disease (KBD) is a chronic osteochondropathy. The pathogenesis of growth and development failure of hand of KBD remains elusive now. In this study, we conducted a two-stage genome-wide association study (GWAS) of palmar length-width ratio (LWR) of KBD, totally including 493 study subjects. Affymetrix Genome Wide Human SNP Array 6.0 was applied for genome-wide SNP genotyping of 90 KBD patients. Association analysis was conducted by PLINK. Imputation analysis was performed by IMPUTE ag ...[more]

PMID: 28059113

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Project description:Understanding how genomes encode complex cellular and organismal behaviors has become the outstanding challenge of modern genetics. Unlike classical screening methods, analysis of genetic variation that occurs naturally in wild populations can enable rapid, genome-scale mapping of genotype to phenotype with a medium-throughput experimental design. Here we describe the results of the first genome-wide association study (GWAS) used to identify novel loci underlying trait variation in a microbial eukaryote, harnessing wild isolates of the filamentous fungus Neurospora crassa. We genotyped each of a population of wild Louisiana strains at 1 million genetic loci genome-wide, and we used these genotypes to map genetic determinants of microbial communication. In N. crassa, germinated asexual spores (germlings) sense the presence of other germlings, grow toward them in a coordinated fashion, and fuse. We evaluated germlings of each strain for their ability to chemically sense, chemotropically seek, and undergo cell fusion, and we subjected these trait measurements to GWAS. This analysis identified one gene, NCU04379 (cse-1, encoding a homolog of a neuronal calcium sensor), at which inheritance was strongly associated with the efficiency of germling communication. Deletion of cse-1 significantly impaired germling communication and fusion, and two genes encoding predicted interaction partners of CSE1 were also required for the communication trait. Additionally, mining our association results for signaling and secretion genes with a potential role in germling communication, we validated six more previously unknown molecular players, including a secreted protease and two other genes whose deletion conferred a novel phenotype of increased communication and multi-germling fusion. Our results establish protein secretion as a linchpin of germling communication in N. crassa and shed light on the regulation of communication molecules in this fungus. Our study demonstrates the power of population-genetic analyses for the rapid identification of genes contributing to complex traits in microbial species.

Dataset Information

Genome-wide association study identifies COL2A1 locus involved in the hand development failure of Kashin-Beck disease.

Publications

Genome-wide association study identifies COL2A1 locus involved in the hand development failure of Kashin-Beck disease.

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