Exome sequencing identified FGF12 as a novel candidate gene for Kashin-Beck disease

详细信息    查看全文

• 作者：Feng Zhang ; Lanlan Dai ; Weimin Lin ; Wenyu Wang…
• 关键词：Kashin ; Beck disease ; Exome sequencing ; Genome ; wide association study ; Fibroblast growth factor
• 刊名：Functional & Integrative Genomics
• 出版年：2016
• 出版时间：January 2016
• 年：2016
• 卷：16
• 期：1
• 页码：13-17
• 全文大小：365 KB
• 参考文献：Chen Z, Zheng G, Ghosh K, Li Z (2005) Linkage disequilibrium mapping of quantitative-trait loci by selective genotyping. Am J Hum Genet 77:661–669PubMedCentral CrossRef PubMed
  Cohn MJ, Izpisua-Belmonte JC, Abud H, Heath JK, Tickle C (1995) Fibroblast growth factors induce additional limb development from the flank of chick embryos. Cell 80:739–746CrossRef PubMed
  Du XH, Dai XX, Xia Song R, Zou XZ, Yan Sun W, Mo XY, Lu Bai G, Xiong YM (2012) SNP and mRNA expression for glutathione peroxidase 4 in Kashin-Beck disease. Br J Nutr 107:164–169CrossRef PubMed
  Du XA, Wang HM, Dai XX, Kou Y, Wu RP, Chen Q, Cao JL, Mo XY, Xiong YM (2015) Role of selenoprotein S (SEPS1) -105G>A polymorphisms and PI3K/Akt signaling pathway in Kashin-Beck disease. Osteoarthr Cartil 23:210–216CrossRef PubMed
  Duan C, Guo X, Zhang XD, Yu HJ, Yan H, Gao Y, Ma WJ, Gao ZQ, Xu P, Lammi M (2010) Comparative analysis of gene expression profiles between primary knee osteoarthritis and an osteoarthritis endemic to Northwestern China, Kashin-Beck disease. Arthritis Rheum 62:771–780CrossRef PubMed
  Guo X, Zuo H, Cao CX, Zhang Y, Geng D, Zhang ZT, Zhang YG, von der Mark K, von der Mark H (2006) Abnormal expression of Col X, PTHrP, TGF-beta, bFGF, and VEGF in cartilage with Kashin-Beck disease. J Bone Miner Metab 24:319–328CrossRef PubMed
  Huang L, Shi Y, Lu F, Zheng H, Liu X, Gong B, Yang J, Lin Y, Cheng J, Ma S, Lin H, Yang Z (2013) Association study of polymorphisms in selenoprotein genes and Kashin-Beck disease and serum selenium/iodine concentration in a Tibetan population. PLoS One 8, e71411PubMedCentral CrossRef PubMed
  Lu AL, Guo X, Aisha MM, Shi XW, Zhang YZ, Zhang YY (2011) Kashin-Beck disease and Sayiwak disease in China: prevalence and a comparison of the clinical manifestations, familial aggregation, and heritability. Bone 48:347–353CrossRef PubMed
  Mariani FV, Ahn CP, Martin GR (2008) Genetic evidence that FGFs have an instructive role in limb proximal-distal patterning. Nature 453:401–405PubMedCentral CrossRef PubMed
  Price AL, Patterson NJ, Plenge RM, Weinblatt ME, Shadick NA, Reich D (2006) Principal components analysis corrects for stratification in genome-wide association studies. Nat Genet 38:904–909CrossRef PubMed
  Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender D, Maller J, Sklar P, de Bakker PI, Daly MJ, Sham PC (2007) PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet 81:559–575PubMedCentral CrossRef PubMed
  Qi H, Jin M, Duan Y, Du X, Zhang Y, Ren F, Wang Y, Tian Q, Wang X, Wang Q, Zhu Y, Xie Y, Liu C, Cao X, Mishina Y, Chen D, Deng CX, Chang Z, Chen L (2014) FGFR3 induces degradation of BMP type I receptor to regulate skeletal development. Biochim Biophys Acta 1843:1237–1247PubMedCentral CrossRef PubMed
  Shi Y, Lu F, Liu X, Wang Y, Huang L, Long W, Lv B, Zhang K, Ma S, Lin H, Cheng J, Zhou B, Hu M, Deng J, Zhu J, Hao P, Yang X, Zeng M, Wang X, Shen S, Yang Z (2011) Genetic variants in the HLA-DRB1 gene are associated with Kashin-Beck disease in the Tibetan population. Arthritis Rheum 63:3408–3416CrossRef PubMed
  Shi X, Zhang F, Lv A, Wen Y, Guo X (2015) COL9A1 gene polymorphism is associated with Kashin-Beck disease in a northwest Chinese Han population. PLoS One 10, e0120365PubMedCentral CrossRef PubMed
  Stone R (2009) Diseases. A medical mystery in middle China. Science 324:1378–1381CrossRef PubMed
  Thompson ER, Doyle MA, Ryland GL, Rowley SM, Choong DY, Tothill RW, Thorne H, Barnes DR, Li J, Ellul J, Philip GK, Antill YC, James PA, Trainer AH, Mitchell G, Campbell IG (2012) Exome sequencing identifies rare deleterious mutations in DNA repair genes FANCC and BLM as potential breast cancer susceptibility alleles. PLoS Genet 8, e1002894PubMedCentral CrossRef PubMed
  Varela I, Tarpey P, Raine K, Huang D, Ong CK, Stephens P, Davies H, Jones D, Lin ML, Teague J, Bignell G, Butler A, Cho J, Dalgliesh GL, Galappaththige D, Greenman C, Hardy C, Jia M, Latimer C, Lau KW, Marshall J, McLaren S, Menzies A, Mudie L, Stebbings L, Largaespada DA, Wessels LF, Richard S, Kahnoski RJ, Anema J, Tuveson DA, Perez-Mancera PA, Mustonen V, Fischer A, Adams DJ, Rust A, Chan-on W, Subimerb C, Dykema K, Furge K, Campbell PJ, Teh BT, Stratton MR, Futreal PA (2011) Exome sequencing identifies frequent mutation of the SWI/SNF complex gene PBRM1 in renal carcinoma. Nature 469:539–542PubMedCentral CrossRef PubMed
  Wang W, Guo X, Chen J, Xu P, Lammi MJ (2008) Morphology and phenotype expression of types I, II, III, and X collagen and MMP-13 of chondrocytes cultured from articular cartilage of Kashin-Beck disease. J Rheumatol 35:696–702PubMed
  Wang K, Zhang H, Ma D, Bucan M, Glessner JT, Abrahams BS, Salyakina D, Imielinski M, Bradfield JP, Sleiman PM, Kim CE, Hou C, Frackelton E, Chiavacci R, Takahashi N, Sakurai T, Rappaport E, Lajonchere CM, Munson J, Estes A, Korvatska O, Piven J, Sonnenblick LI, Alvarez Retuerto AI, Herman EI, Dong H, Hutman T, Sigman M, Ozonoff S, Klin A, Owley T, Sweeney JA, Brune CW, Cantor RM, Bernier R, Gilbert JR, Cuccaro ML, McMahon WM, Miller J, State MW, Wassink TH, Coon H, Levy SE, Schultz RT, Nurnberger JI, Haines JL, Sutcliffe JS, Cook EH, Minshew NJ, Buxbaum JD, Dawson G, Grant SF, Geschwind DH, Pericak-Vance MA, Schellenberg GD, Hakonarson H (2009) Common genetic variants on 5p14.1 associate with autism spectrum disorders. Nature 459:528–533PubMedCentral CrossRef PubMed
  Wang JL, Yang X, Xia K, Hu ZM, Weng L, Jin X, Jiang H, Zhang P, Shen L, Guo JF, Li N, Li YR, Lei LF, Zhou J, Du J, Zhou YF, Pan Q, Wang J, Li RQ, Tang BS (2010) TGM6 identified as a novel causative gene of spinocerebellar ataxias using exome sequencing. Brain 133:3510–3518CrossRef PubMed
  Wu CH, Fallini C, Ticozzi N, Keagle PJ, Sapp PC, Piotrowska K, Lowe P, Koppers M, McKenna-Yasek D, Baron DM, Kost JE, Gonzalez-Perez P, Fox AD, Adams J, Taroni F, Tiloca C, Leclerc AL, Chafe SC, Mangroo D, Moore MJ, Zitzewitz JA, Xu ZS, van den Berg LH, Glass JD, Siciliano G, Cirulli ET, Goldstein DB, Salachas F, Meininger V, Rossoll W, Ratti A, Gellera C, Bosco DA, Bassell GJ, Silani V, Drory VE, Brown RH Jr, Landers JE (2012) Mutations in the profilin 1 gene cause familial amyotrophic lateral sclerosis. Nature 488:499–503PubMedCentral CrossRef PubMed
  Xiong YM, Mo XY, Zou XZ, Song RX, Sun WY, Lu W, Chen Q, Yu YX, Zang WJ (2010) Association study between polymorphisms in selenoprotein genes and susceptibility to Kashin-Beck disease. Osteoarthr Cartil 18:817–824CrossRef PubMed
  Yang Z, Xu Y, Luo H, Ma X, Wang Q, Wang Y, Deng W, Jiang T, Sun G, He T, Hu J, Li Y, Wang J, Li T, Hu X (2014) Whole-exome sequencing for the identification of susceptibility genes of Kashin-Beck disease. PLoS One 9, e92298PubMedCentral CrossRef PubMed
  Zhang SQ, Jiang T, Li M, Zhang X, Ren YQ, Wei SC, Sun LD, Cheng H, Li Y, Yin XY, Hu ZM, Wang ZY, Liu Y, Guo BR, Tang HY, Tang XF, Ding YT, Wang JB, Li P, Wu BY, Wang W, Yuan XF, Hou JS, Ha WW, Wang WJ, Zhai YJ, Wang J, Qian FF, Zhou FS, Chen G, Zuo XB, Zheng XD, Sheng YJ, Gao JP, Liang B, Zhu J, Xiao FL, Wang PG, Cui Y, Li H, Liu SX, Gao M, Fan X, Shen SK, Zeng M, Sun GQ, Xu Y, Hu JC, He TT, Li YR, Yang HM, Yu ZY, Zhang HF, Hu X, Yang K, Zhao SX, Zhou YW, Liu JJ, Du WD, Zhang L, Xia K, Yang S, Zhang XJ (2012) Exome sequencing identifies MVK mutations in disseminated superficial actinic porokeratosis. Nat Genet 44:1156–1160CrossRef PubMed
  Zhang F, Guo X, Zhang Y, Wen Y, Wang W, Wang S, Yang T, Shen H, Chen X, Tian Q, Tan L, Deng HW (2014) Genome-wide copy number variation study and gene expression analysis identify ABI3BP as a susceptibility gene for Kashin-Beck disease. Hum Genet 133:793–799CrossRef PubMed
  Zhang F, Wen Y, Guo X, Zhang Y, Wang X, Yang T, Shen H, Chen X, Tian Q, Deng HW (2015) Genome-wide association study identifies ITPR2 as a susceptibility gene for Kashin-Beck disease in Han Chinese. Arthritis Rheumatol 67:176–181CrossRef PubMed
  Zhao QM, Guo X, Lai JH, Tan WH, Wang WZ, Dang XQ (2012) Association of TNF-alpha and Fas gene promoter polymorphism with the risk of Kashin-Beck disease in Northwest Chinese population. Clin Rheumatol 31:1051–1057CrossRef PubMed
  
• 作者单位：Feng Zhang (1)
  Lanlan Dai (2)
  Weimin Lin (3)
  Wenyu Wang (1)
  Xuanzhu Liu (2)
  Jianguo Zhang (2)
  Tielin Yang (4)
  Xiaogang Liu (4)
  Hui Shen (5) (6)
  Xiangding Chen (7)
  Lijun Tan (7)
  Qing Tian (5) (6)
  Hong-Wen Deng (5) (6)
  Xun Xu (2)
  Xiong Guo (1)
  
  1. Key Laboratory of Trace Elements and Endemic Diseases of Ministry of Health, School of Public Health, Health Science Center, Xi’an Jiaotong University, Xi’an, People’s Republic of China
  2. BGI-Shenzhen, Shenzhen, 518083, China
  3. Department of Nephrology and Traditional Chinese Medicine, The People’s Liberating Army 451 Hospital, Xi’an, People’s Republic of China
  4. Key Laboratory of Biomedical Information Engineering of Ministry of Education, and Institute of Molecular Genetics, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an, People’s Republic of China
  5. Department of Biostatistics and Bioinformatics, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, USA
  6. Center for Bioinformatics and Genomics, Tulane University, New Orleans, LA, USA
  7. Laboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal University, Changsha, People’s Republic of China
  
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Life Sciences
  Cell Biology
  Plant Genetics and Genomics
  Microbial Genetics and Genomics
  Biochemistry
  Bioinformatics
  Animal Genetics and Genomics
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：1438-7948

文摘

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. Keywords Kashin-Beck disease Exome sequencing Genome-wide association study Fibroblast growth factor