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Origin of the PSEN1 E280A mutation causing early‐onset Alzheimer's disease
Author(s) -
Lalli Matthew A.,
Cox Hannah C.,
Arcila Mary L.,
Cadavid Liliana,
Moreno Sonia,
Garcia Gloria,
Madrigal Lucia,
Reiman Eric M.,
ArcosBurgos Mauricio,
Bedoya Gabriel,
Brunkow Mary E.,
Glusman Gustavo,
Roach Jared C.,
Hood Leroy,
Kosik Kenneth S.,
Lopera Francisco
Publication year - 2014
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2013.09.005
Subject(s) - early onset alzheimer's disease , disease , psen1 , mutation , alzheimer's disease , medicine , genetics , presenilin , biology , gene
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.