A rare variant in the osteoarthritis-associated locus GDF5 is functional and reveals a site that can be manipulated to modulate GDF5 expression

European Journal of Human Genetics

Volumn 21, Issue 5, 2013, Pages 517-521

  Dodd, Andrew W ^a   Syddall, Catherine M ^a   Loughlin, John ^a  

^a NEWCASTLE UNIVERSITY   (United Kingdom)

Author keywords

Association; EMSA; Expression; GDF5; Osteoarthritis; YY1

Indexed keywords

GROWTH DIFFERENTIATION FACTOR 5; TRANS ACTING FACTOR; TRANSCRIPTION FACTOR YY1;

ALLELE; ARTICLE; CONTROLLED STUDY; FUNCTIONAL ASSESSMENT; GEL MOBILITY SHIFT ASSAY; GENE CONSTRUCT; GENE EXPRESSION; GENE LOCUS; GENE SEQUENCE; GENE SILENCING; GENETIC ASSOCIATION; GENETIC VARIABILITY; HUMAN; HUMAN CELL; OSTEOARTHRITIS; PRIORITY JOURNAL; PROMOTER REGION; PROTEIN EXPRESSION; REPORTER GENE; TRANSCRIPTION INITIATION SITE;

CELL LINE, TUMOR; CHONDROCYTES; DNA PRIMERS; ELECTROPHORETIC MOBILITY SHIFT ASSAY; GENE EXPRESSION REGULATION; GENE KNOCKDOWN TECHNIQUES; GROWTH DIFFERENTIATION FACTOR 5; HIGH-THROUGHPUT NUCLEOTIDE SEQUENCING; HUMANS; LUCIFERASES; OSTEOARTHRITIS; PLASMIDS; POLYMORPHISM, SINGLE NUCLEOTIDE; PROMOTER REGIONS, GENETIC; YY1 TRANSCRIPTION FACTOR;

EID: 84876688803     PISSN: 10184813     EISSN: 14765438     Source Type: Journal    
DOI: 10.1038/ejhg.2012.197     Document Type: Article

References (20)

1. Mikic B: Multiple effects of GDF-5 deficiency on skeletal tissues: implications for therapeutic bioengineering. Ann Biomed Eng 2004; 32: 466-476.
2. Thomas JT, Lin K, Nandedkar M, Camargo M, Cervenka J, Luyten FP: A human chondrodysplasia due to a mutation in a TGF-b superfamily member. Nat Genet 1996; 12: 315-317.
3. Thomas JT, Kilpatrick MW, Lin K et al: Disruption of human limb morphogenesis by a dominant negative mutation in CDMP1. Nat Genet 1997; 17: 58-64. (Pubitemid 27377532)
4. Polinkovsky A, Robin NH, Thomas JT et al: Mutations in CDMP1 cause autosomal dominant brachydactyly type C. Nat Genet 1997; 17: 18-19.
5. Settle SH, Rountree RB, Sinha A, Thacker A, Higgins K, Kingsley DM: Multiple joint and skeletal patterning defects caused by single and double mutations in the Gdf6 and Gdf5 genes. Dev Biol 2003; 254: 116-130. (Pubitemid 36259876)
6. Daans M, Luyten FP, Lories RJ: GDF5 deficiency in mice is associated with instabilitydriven joint damage, gait and subchondral bone changes. Ann Rheum Dis 2011; 70: 208-213.
7. Miyamoto Y, Mabuchi A, Shi D et al: A functional polymorphism in the 50 UTR of GDF5 is associated with susceptibility to osteoarthritis. Nat Genet 2007; 39: 529-533. (Pubitemid 46514783)
8. Brandt KD, Dieppe P, Radin E: Etiopathogenesis of osteoarthritis. Rheum Dis Clin North Am 2008; 34: 531-559.
9. Chapman K, Takahashi A, Meulenbelt I et al: A meta-analysis of European and Asian cohorts reveals a global role of a functional SNP in the 5' UTR of GDF5 with osteoarthritis susceptibility. Hum Mol Genet 2008; 17: 1497-1504. (Pubitemid 351627345)
10. Southam L, Rodriguez-Lopez J, Wilkins JM et al: An SNP in the 5'-UTR of GDF5 is associated with osteoarthritis susceptibility in Europeans and with in vivo differences in allelic expression in articular cartilage. Hum Mol Genet 2007; 16: 2226-2232. (Pubitemid 47354904)
11. Egli R, Southam L, Wilkins JM et al: Functional analysis of the osteoarthritis susceptibility-associated GDF5 regulatory polymorphism. Arthritis Rheum 2009; 60: 2055-2064.
12. Lango Allen H, Estrada K, Lettre G et al: Hundreds of variants clustered in genomic loci and biological pathways affect human height. Nature 2010; 467: 832-838.
13. Bodmer W, Bonilla C: Common and rare variants in multifactorial susceptibility to common diseases. Nat Genet 2008; 40: 695-701. (Pubitemid 351748875)
14. Dodd AW, Rodriguez-Fontenla C, Calaza M et al: Deep sequencing of GDF5 reveals the absence of rare variants at this important osteoarthritis susceptibility locus. Osteoarthritis Cartilage 2011; 19: 430-434.
15. Ratnayake M, Reynard LN, Raine EVA, Santibanez-Koref M, Loughlin J: Allelic expression analysis of the osteoarthritis susceptibility locus that maps to MICAL3. BMC Med Genet 2012; 13: 12.
16. Reynard LN, Bui C, Canty-Laird EG, Young DA, Loughlin J: Expression of the osteoarthritis-associated gene GDF5 is modulated epigenetically by DNA methylation. Hum Mol Genet 2011; 20: 3450-3460.
17. He Y, Casaccia-Bonnefil P: The Yin and Yang of YY1 in the nervous system. J Neurochem 2008; 106: 1493-1502.
18. Donohoe ME, Zhang X, McGinnis L, Biggers J, Li E, Shi Y: Targeted disruption of mouse Yin Yang 1 transcription factor results in peri-implantation lethality. Mol Cell Biol 1999; 19: 7237-7244. (Pubitemid 29441903)
19. Roy A, McDonald PR, Sittampalam S, Chaguturu R: Open access high throughput drug discovery in the public domain: a Mount Everest in the making. Curr Pharm Biotechnol 2010; 11: 764-778.
20. Tennessen JA, Bigham AW, O'Connor TD et al: Evolution and functional impact of rare coding variation from deep sequencing of human exomes. Science 2012; 337: 64-69.