Journal article
In-frame seven amino-acid duplication in AIP arose over the last 3000 years, disrupts protein interaction and stability and is associated with gigantism
R Salvatori, S Radian, Y Diekmann, D Iacovazzo, A David, P Gabrovska, G Grassi, AM Bussell, K Stals, A Weber, R Quinton, EC Crowne, V Corazzini, L Metherell, T Kearney, D Du Plessis, AK Sinha, A Baborie, AL Lecoq, P Chanson Show all
European Journal of Endocrinology | BIOSCIENTIFICA LTD | Published : 2017
DOI: 10.1530/EJE-17-0293
Abstract
Objective: Mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene are associated with pituitary adenoma, acromegaly and gigantism. Identical alleles in unrelated pedigrees could be inherited from a common ancestor or result from recurrent mutation events. Design and methods: Observational, inferential and experimental study, including: AIP mutation testing; reconstruction of 14 AIP-region (8.3 Mbp) haplotypes; coalescent-based approximate Bayesian estimation of the time to most recent common ancestor (tMRCA) of the derived allele; forward population simulations to estimate current number of allele carriers; proposal of mutation mechanism; protein structure predictions; co-..
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Awarded by Medical Research Council
Funding Acknowledgements
S R was supported by the EC-REA Marie Sklodowska-Curie IEF postdoctoral fellowship (grant 303006/2011). A D was supported by an MRC postdoctoral fellowship (grant MR/K021613/1). D I is supported by a Diabetes UK George Alberti Clinical Research Training Fellowship. M K's work on familial pituitary adenomas is supported by the Medical Research Council, Barts and the London Charity and Pfizer Ltd.