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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
  • Arcos-Burgos, Mauricio
  • Bedoya, Gabriel
  • Brunkow, Mary E
  • Glusman, Gustavo
  • Roach, Jared C
  • Hood, Leroy
  • Kosik, Kenneth S
  • Lopera, Francisco
  • et al.


A mutation in presenilin 1 (E280A) causes early-onset Alzheimer's disease. Understanding the origin of this mutation will inform medical genetics.


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.


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.


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.

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