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Combined approach for finding susceptibility genes in DISH/chondrocalcinosis families: whole-genome-wide linkage and IBS/IBD studies

Citation

Couto, AR and Parreira, B and Thomson, R and Soares, M and Power, DM and Stankovich, J and Armas, JB and Brown, MA, Combined approach for finding susceptibility genes in DISH/chondrocalcinosis families: whole-genome-wide linkage and IBS/IBD studies, Human Genome Variation, 4 Article 17041. ISSN 2054-345X (2017) [Refereed Article]


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The Author(s) 2017. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) http://creativecommons.org/licenses/by-nc-nd/4.0/

DOI: doi:10.1038/hgv.2017.41

Abstract

Twelve families with exuberant and early-onset calcium pyrophosphate dehydrate chondrocalcinosis (CC) and diffuse idiopathic skeletal hyperostosis (DISH), hereafter designated DISH/CC, were identified in Terceira Island, the Azores, Portugal. Ninety-two (92) individuals from these families were selected for whole-genome-wide linkage analysis. An identity-by-descent (IBD) analysis was performed in 10 individuals from 5 of the investigated pedigrees. The chromosome area with the maximal logarithm of the odds score (1.32; P=0.007) was not identified using the IBD/identity-by-state (IBS) analysis; therefore, it was not investigated further. From the IBD/IBS analysis, two candidate genes, LEMD3 and RSPO4, were identified and sequenced. Nine genetic variants were identified in the RSPO4 gene; one regulatory variant (rs146447064) was significantly more frequent in control individuals than in DISH/CC patients (P=0.03). Four variants were identified in LEMD3, and the rs201930700 variant was further investigated using segregation analysis. None of the genetic variants in RSPO4 or LEMD3 segregated within the studied families. Therefore, although a major genetic effect was shown to determine DISH/CC occurrence within these families, the specific genetic variants involved were not identified.

Item Details

Item Type:Refereed Article
Keywords:susceptibility genes, chondrocalcinosis, diffuse idiopathic skeletal hyperostosis, DISH, LEMD3, RSPO4
Research Division:Medical and Health Sciences
Research Group:Clinical Sciences
Research Field:Medical Genetics (excl. Cancer Genetics)
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Inherited Diseases (incl. Gene Therapy)
UTAS Author:Stankovich, J (Dr Jim Stankovich)
ID Code:123399
Year Published:2017
Deposited By:Menzies Institute for Medical Research
Deposited On:2018-01-04
Last Modified:2018-07-23
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