Genetic linkage analysis of a large family identifies
ATPases Associated with Diverse Cellular Activities
/ genetics
Alleles
Amino Acid Substitution
Blood Pressure
Chromosomes, Human, Pair 2
Familial Primary Pulmonary Hypertension
/ diagnosis
Family
Genetic Association Studies
Genetic Linkage
Genetic Predisposition to Disease
Genome-Wide Association Study
Genotype
Hemodynamics
Heterozygote
Humans
Linkage Disequilibrium
Microtubule-Associated Proteins
/ genetics
Mutation
Pedigree
Penetrance
Phenotype
Polymorphism, Single Nucleotide
clinical genetics
genetic modifier
heritable pulmonary arterial hypertension
linkage
reduced penetrance
Journal
Journal of medical genetics
ISSN: 1468-6244
Titre abrégé: J Med Genet
Pays: England
ID NLM: 2985087R
Informations de publication
Date de publication:
07 2019
07 2019
Historique:
received:
08
08
2018
revised:
12
02
2019
accepted:
16
02
2019
pubmed:
22
3
2019
medline:
4
6
2020
entrez:
22
3
2019
Statut:
ppublish
Résumé
Mapping the genetic component of molecular mechanisms responsible for the reduced penetrance (RP) of rare disorders constitutes one of the most challenging problems in human genetics. Heritable pulmonary arterial hypertension (PAH) is one such disorder characterised by rare mutations mostly occurring in the bone morphogenetic protein receptor type 2 ( We performed a linkage analysis on the genotyping data to search for genetic modifiers of penetrance. Using functional genomics data, we characterised the candidate region identified by linkage analysis. We also predicted the haplotype segregation within the family. We identified a candidate chromosome region in 2q24.3, 38 Mb upstream from Our results suggest that the genetic modifier acts through
Sections du résumé
BACKGROUND
Mapping the genetic component of molecular mechanisms responsible for the reduced penetrance (RP) of rare disorders constitutes one of the most challenging problems in human genetics. Heritable pulmonary arterial hypertension (PAH) is one such disorder characterised by rare mutations mostly occurring in the bone morphogenetic protein receptor type 2 (
METHODS
We performed a linkage analysis on the genotyping data to search for genetic modifiers of penetrance. Using functional genomics data, we characterised the candidate region identified by linkage analysis. We also predicted the haplotype segregation within the family.
RESULTS
We identified a candidate chromosome region in 2q24.3, 38 Mb upstream from
CONCLUSION
Our results suggest that the genetic modifier acts through
Identifiants
pubmed: 30894412
pii: jmedgenet-2018-105669
doi: 10.1136/jmedgenet-2018-105669
doi:
Substances chimiques
Microtubule-Associated Proteins
0
ATPases Associated with Diverse Cellular Activities
EC 3.6.4.-
FIGN protein, human
EC 3.6.4.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
481-490Informations de copyright
© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.
Déclaration de conflit d'intérêts
Competing interests: None declared.