Origin of the PSEN1 E280A mutation causing early‐onset Alzheimer's disease
- 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
Published Web Location
https://www.ncbi.nlm.nih.gov/pubmed/?term=Origin+of+the+PSEN1+E280A+mutation+causing+early-onset+Alzheimer's+diseaseAbstract
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.
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