Ontology highlight
ABSTRACT: Background
Papillary thyroid carcinoma (PTC) shows high heritability, yet efforts to find predisposing genes have been largely negative.Objectives
The objective of this study was to identify susceptibility genes for PTC.Methods
A genome-wide linkage analysis was performed in 38 families. Targeted association study and screening were performed in 2 large cohorts of PTC patients and controls. Candidate DNA variants were tested in functional studies.Results
Linkage analysis and association studies identified the Slit-Robo Rho GTPase activating protein 1 gene (SRGAP1) in the linkage peak as a candidate gene. Two missense variants, Q149H and A275T, localized in the Fes/CIP4 homology domain segregated with the disease in 1 family each. One missense variant, R617C, located in the RhoGAP domain occurred in 1 family. Biochemical assays demonstrated that the ability to inactivate CDC42, a key function of SRGAP1, was severely impaired by the Q149H and R617C variants.Conclusions
Our findings suggest that SRGAP1 is a candidate gene in PTC susceptibility. SRGAP1 is likely a low-penetrant gene, possibly of a modifier type.
SUBMITTER: He H
PROVIDER: S-EPMC3644596 | biostudies-literature | 2013 May
REPOSITORIES: biostudies-literature
He Huiling H Bronisz Agnieszka A Liyanarachchi Sandya S Nagy Rebecca R Li Wei W Huang Yungui Y Akagi Keiko K Saji Motoyasu M Kula Dorota D Wojcicka Anna A Sebastian Nikhil N Wen Bernard B Puch Zbigniew Z Kalemba Michal M Stachlewska Elzbieta E Czetwertynska Malgorzata M Dlugosinska Joanna J Dymecka Kinga K Ploski Rafal R Krawczyk Marek M Morrison Patrick J PJ Ringel Matthew D MD Kloos Richard T RT Jazdzewski Krystian K Symer David E DE Vieland Veronica J VJ Ostrowski Michael M Jarząb Barbara B de la Chapelle Albert A
The Journal of clinical endocrinology and metabolism 20130328 5
<h4>Background</h4>Papillary thyroid carcinoma (PTC) shows high heritability, yet efforts to find predisposing genes have been largely negative.<h4>Objectives</h4>The objective of this study was to identify susceptibility genes for PTC.<h4>Methods</h4>A genome-wide linkage analysis was performed in 38 families. Targeted association study and screening were performed in 2 large cohorts of PTC patients and controls. Candidate DNA variants were tested in functional studies.<h4>Results</h4>Linkage a ...[more]