Origin of the PSEN1 E280A mutation causing early–onset Alzheimer’s disease

ABSTRACT: Background: A mutation in presenilin 1 (E280A) causes early-onset Alzheimer's disease. Understanding the origin of this mutation will inform medical genetics. Methods: We sequenced the genomes of 102 individuals from Antioquia, Colombia. We applied identity-by-descent analysis to identify regions of common ancestry. We estimated the age of the E280A mutation and the local ancestry of the haplotype harboring this mutation. Results: All affected individuals share a minimal haplotype of 1.8 Mb containing E280A. We estimate a time to most recent common ancestor of E280A of 10 (95% credible interval, 7.2-12.6) generations. We date the de novo mutation event to 15 (95% credible interval, 11-25) generations ago. We infer a western European geographic origin of the shared haplotype. Conclusions: The age and geographic origin of E280A are consistent with a single founder dating from the time of the Spanish Conquistadors who began colonizing Colombia during the early 16th century. Keywords: Alzheimer’s disease; PSEN1; population genetics; whole-genome sequencing.

• Autores: Arcila, Mary L.; Cadavid Celis, Liliana; Moreno Másmela, Sonia; García Ospina, Gloria Patricia; Madrigal, Lucía; Arcos Burgos, Oscar Mauricio; Bedoya Berrío, Gabriel de Jesús; Lopera Restrepo, Francisco Javier; Lalli, Matthew A.; Cox, Hannah C.; Brunkow, Mary E.; Glusman, Gustavo; Roach, Jared C.; Hood, Leroy; Kosik, Kenneth S.; Reiman, Eric M.
• Tipo de recurso: Article of investigation
• Fecha de publicación: 2014
• Institución: Universidad de Antioquia
• Repositorio: Repositorio UdeA
• Idioma: eng
• OAI Identifier: oai:bibliotecadigital.udea.edu.co:10495/39585
• Acceso en línea: https://hdl.handle.net/10495/39585
• Palabra clave: Edad de Inicio; Age of Onset; Enfermedad de Alzheimer; Alzheimer Disease; Efecto Fundador; Founder Effect; Predisposición Genética a la Enfermedad; Genetic Predisposition to Disease; Haplotipos; Haplotypes; Patrón de Herencia; Inheritance Patterns; Presenilina-1; Presenilin-1; Colombia; https://id.nlm.nih.gov/mesh/D017668; https://id.nlm.nih.gov/mesh/D000544; https://id.nlm.nih.gov/mesh/D018703; https://id.nlm.nih.gov/mesh/D020022; https://id.nlm.nih.gov/mesh/D006239; https://id.nlm.nih.gov/mesh/D040582; https://id.nlm.nih.gov/mesh/D003105
• Rights: openAccess
• License: https://creativecommons.org/licenses/by-nc-nd/4.0/