PMID- 21281725 OWN - NLM STAT- MEDLINE DCOM- 20110617 LR - 20161125 IS - 1522-9653 (Electronic) IS - 1063-4584 (Linking) VI - 19 IP - 4 DP - 2011 Apr TI - Deep sequencing of GDF5 reveals the absence of rare variants at this important osteoarthritis susceptibility locus. PG - 430-4 LID - 10.1016/j.joca.2011.01.014 [doi] AB - OBJECTIVE: The common single nucleotide polymorphism (SNP) rs143383 in the 5' untranslated region (5'UTR) of growth and differentiation factor 5 (GDF5) is strongly associated with osteoarthritis (OA) and influences GDF5 allelic expression in vitro and in the joint tissues of OA patients. This effect is modulated in cis by another common SNP, also located within the 5'UTR, whilst a common SNP in the 3'UTR influences allelic expression independent of rs143383. DNA variants can be common, rare or extremely rare/unique. To therefore enhance our understanding of the allelic architecture of this very important OA susceptibility locus we sequenced the gene for potentially functional and novel rare variants. METHOD: Using the Sanger method we sequenced GDF5 in 992 OA patients and 944 controls, with DNA changes identified by sequencing software. We encompassed the protein-coding region of the two GDF5 exons, both untranslated regions and approximately 100 bp of the proximal promoter of the gene. RESULTS: We detected 13 variants. Six were extremely rare with minor allele frequencies (MAFs) of