Cargando…

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

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 sele...

Descripción completa

Detalles Bibliográficos
Autores principales: Couto, Ana Rita, Parreira, Bruna, Thomson, Russell, Soares, Marta, Power, Deborah M, Stankovich, Jim, Armas, Jácome Bruges, Brown, Matthew A
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5666909/
https://www.ncbi.nlm.nih.gov/pubmed/29104755
http://dx.doi.org/10.1038/hgv.2017.41
_version_ 1783275401392422912
author Couto, Ana Rita
Parreira, Bruna
Thomson, Russell
Soares, Marta
Power, Deborah M
Stankovich, Jim
Armas, Jácome Bruges
Brown, Matthew A
author_facet Couto, Ana Rita
Parreira, Bruna
Thomson, Russell
Soares, Marta
Power, Deborah M
Stankovich, Jim
Armas, Jácome Bruges
Brown, Matthew A
author_sort Couto, Ana Rita
collection PubMed
description 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.
format Online
Article
Text
id pubmed-5666909
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher Nature Publishing Group
record_format MEDLINE/PubMed
spelling pubmed-56669092017-11-03 Combined approach for finding susceptibility genes in DISH/chondrocalcinosis families: whole-genome-wide linkage and IBS/IBD studies Couto, Ana Rita Parreira, Bruna Thomson, Russell Soares, Marta Power, Deborah M Stankovich, Jim Armas, Jácome Bruges Brown, Matthew A Hum Genome Var Article 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. Nature Publishing Group 2017-11-02 /pmc/articles/PMC5666909/ /pubmed/29104755 http://dx.doi.org/10.1038/hgv.2017.41 Text en Copyright © 2017 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/
spellingShingle Article
Couto, Ana Rita
Parreira, Bruna
Thomson, Russell
Soares, Marta
Power, Deborah M
Stankovich, Jim
Armas, Jácome Bruges
Brown, Matthew A
Combined approach for finding susceptibility genes in DISH/chondrocalcinosis families: whole-genome-wide linkage and IBS/IBD studies
title Combined approach for finding susceptibility genes in DISH/chondrocalcinosis families: whole-genome-wide linkage and IBS/IBD studies
title_full Combined approach for finding susceptibility genes in DISH/chondrocalcinosis families: whole-genome-wide linkage and IBS/IBD studies
title_fullStr Combined approach for finding susceptibility genes in DISH/chondrocalcinosis families: whole-genome-wide linkage and IBS/IBD studies
title_full_unstemmed Combined approach for finding susceptibility genes in DISH/chondrocalcinosis families: whole-genome-wide linkage and IBS/IBD studies
title_short Combined approach for finding susceptibility genes in DISH/chondrocalcinosis families: whole-genome-wide linkage and IBS/IBD studies
title_sort combined approach for finding susceptibility genes in dish/chondrocalcinosis families: whole-genome-wide linkage and ibs/ibd studies
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5666909/
https://www.ncbi.nlm.nih.gov/pubmed/29104755
http://dx.doi.org/10.1038/hgv.2017.41
work_keys_str_mv AT coutoanarita combinedapproachforfindingsusceptibilitygenesindishchondrocalcinosisfamilieswholegenomewidelinkageandibsibdstudies
AT parreirabruna combinedapproachforfindingsusceptibilitygenesindishchondrocalcinosisfamilieswholegenomewidelinkageandibsibdstudies
AT thomsonrussell combinedapproachforfindingsusceptibilitygenesindishchondrocalcinosisfamilieswholegenomewidelinkageandibsibdstudies
AT soaresmarta combinedapproachforfindingsusceptibilitygenesindishchondrocalcinosisfamilieswholegenomewidelinkageandibsibdstudies
AT powerdeborahm combinedapproachforfindingsusceptibilitygenesindishchondrocalcinosisfamilieswholegenomewidelinkageandibsibdstudies
AT stankovichjim combinedapproachforfindingsusceptibilitygenesindishchondrocalcinosisfamilieswholegenomewidelinkageandibsibdstudies
AT armasjacomebruges combinedapproachforfindingsusceptibilitygenesindishchondrocalcinosisfamilieswholegenomewidelinkageandibsibdstudies
AT brownmatthewa combinedapproachforfindingsusceptibilitygenesindishchondrocalcinosisfamilieswholegenomewidelinkageandibsibdstudies