Whole exome sequencing in identifying genetic factors in musculoskeletal diseases

Thesis event information

Date and time of the thesis defence

Place of the thesis defence

F101, Aapistie 7

Topic of the dissertation

Whole exome sequencing in identifying genetic factors in musculoskeletal diseases

Doctoral candidate

M.Sc. Sini Skarp

Faculty and unit

University of Oulu Graduate School, Faculty of Medicine, Center for Life Course Health Research

Subject of study

Public health science


Professor Hannes Lohi, University of Helsinki


Ph.D. Minna Ruddock, University of Oulu

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New genetic factors underlying musculoskeletal diseases

The research identified rare genetic variants that may predispose to musculoskeletal diseases: osteoarthritis, Modic changes and primary osteoporosis of the spine. Osteoarthritis and lumbar disc degeneration are degenerative diseases affecting joints and spine and Modic changes are a specific phenotype of disc degeneration. Osteoporosis is a disorder causing bone fragility. There are families with a history of early-onset cartilage degradation, disc disorders and bone fragility as well as rare, more severe disorders with these traits as part of the phenotype.

The aim of this study was to identify predisposing genetic factors in Finnish families with three different musculoskeletal phenotypes using whole-exome sequencing that targets the protein-producing part of the genome. Six families were studied here, three diagnosed with hip and knee osteoarthritis, two with Modic changes and one with primary osteoporosis.

The study identified five new identified new candidate genes. One of the identified candidate genes for Modic changes, HSPG2, encodes a structural protein. Others, OLIG3, FIP1L1, MAML1, and ZNF528, participate in the regulation of gene expression. FIPL1 and OLIG3 are new candidate genes for osteoarthritis and MAML1 for Modic changes. A genetic variant in the ZNF528 gene affected the primary osteoporosis phenotype together previously identified deletion in a collagen gene.

These results support the importance of regulatory mechanisms in the pathogenesis of musculoskeletal diseases.
Last updated: 1.3.2023