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

PloS One
Sini SkarpMinna Männikkö

Abstract

Osteoarthritis (OA) is the most common degenerative joint disease and one of the major causes of disability worldwide. It is a multifactorial disorder with a significant genetic component. The heritability of OA has been estimated to be 60% for hip OA and 39% for knee OA. Genetic factors behind OA are still largely unknown. Studying families with strong history of OA, facilitates examining the co-segregation of genetic variation and OA. The aim of this study was to identify new, rare genetic factors and novel candidate genes for OA. Eight patients from three Finnish families with hip and knee OA were studied using whole exome sequencing. We focused on rare exonic variants with predicted pathogenicity and variants located in active promoter or strong enhancer regions. Expression of identified candidate genes were studied in bone and cartilage tissues and the observed variants were investigated using bioinformatic analyses. Two rare variants co-segregated with OA in two families. In Family 8 a missense variant (c.628C>G, p.Arg210Gly) was observed in the OLIG3 gene that encodes a transcription factor known to be associated with rheumatoid arthritis and inflammatory polyarthritis. The Arg210Gly variant was estimated to be pathogeni...Continue Reading

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Citations

Nov 15, 2019·Current Opinion in Rheumatology·Anusha RatneswaranMohit Kapoor
Jun 17, 2020·International Journal of Rheumatic Diseases·Tianyun ZhaoJibin Liu
May 29, 2020·Genetic Testing and Molecular Biomarkers·Tianyun ZhaoJibin Liu

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Datasets Mentioned

BETA
GM12878

Methods Mentioned

BETA
exome sequencing
exome
genotyping
PCR
electrophoresis
acetylation
ChIP-seq

Software Mentioned

MappingQualityRankSumTest
Constraint
- 2
SIFT
QIAxcel ScreenGel Software
RegulomeDB
based Multiple Alignment Tool ( COBALT )
ANNOVAR
PolyPhen
Enhancer Element Locator ( EEL )

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