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Alzheimers Dement. 2014 Oct;10(5 Suppl):S277-S283.e10. doi: 10.1016/j.jalz.2013.09.005. Epub 2013 Nov 13.

Origin of the PSEN1 E280A mutation causing early-onset Alzheimer's disease.

Author information

1
Neuroscience Research Institute, Department of Molecular Cellular Developmental Biology, University of California, Santa Barbara, CA, USA.
2
Institute for Systems Biology, Seattle, WA, USA.
3
Grupo de Neurociencias de Antioquia, Universidad de Antioquia, Medellín, Colombia.
4
Banner Alzheimer's Institute, Phoenix, AZ, USA.
5
Grupo de Neurociencias de Antioquia, Universidad de Antioquia, Medellín, Colombia; Translational Genomics Group, Genome Biology Department, John Curtin School of Medical Research, ANU College of Medicine, Biology and Environment, The Australian National University, Canberra, ACT, Australia.
6
Grupo de Genetica Molecular (GENMOL), Universidad de Antioquia, Medellín, Colombia.
7
Neuroscience Research Institute, Department of Molecular Cellular Developmental Biology, University of California, Santa Barbara, CA, USA. Electronic address: kosik@lifesci.ucsb.edu.

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

PMID:
24239249
PMCID:
PMC4019728
DOI:
10.1016/j.jalz.2013.09.005
[Indexed for MEDLINE]
Free PMC Article

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