Whole exome sequencing in Finnish families identifies new candidate genes for osteoarthritis

• DOI: 10.1371/journal.pone.0203313
• Publication Date: 2018-08-29T19:26:59Z
• Authors: Sini Skarp; Olli-Pekka Kämärä...; Gong-Hong Wei; Eveliina Jakkula; Ilkka Kiviranta; Heikki Kröger; Juha Auvinen; Petri Lehenkari; Leena Ala-Kokko; Minna Männikkö
• Keywords: Candidate gene; Exome

Introduction Osteoarthritis (OA) is the most common degenerative joint disease and one of major causes disability worldwide. It a multifactorial disorder with significant genetic component. The heritability OA has been estimated to be 60% for hip 39% knee OA. Genetic factors behind are still largely unknown. Studying families strong history OA, facilitates examining co-segregation variation aim this study was identify new, rare novel candidate genes Methods Eight patients from three Finnish were studied using whole exome sequencing. We focused on exonic variants predicted pathogenicity located in active promoter or enhancer regions. Expression identified bone cartilage tissues observed investigated bioinformatic analyses. Results Two co-segregated two families. In Family 8 missense variant (c.628C>G, p.Arg210Gly) OLIG3 gene that encodes transcription factor known associated rheumatoid arthritis inflammatory polyarthritis. Arg210Gly pathogenic by Polyphen-2 Mutation taster locus conserved among mammals. 12 (c.-127G>T) start site FIP1L1 gene. participates regulation polyadenylation. c.-127G>T may alter DNA-binding factors. Both, human cartilage. Conclusion revealed have specific roles effect expression other genes. Identified these thus role regulatory events leading