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

Matthew A. Lalli; Hannah C. Cox; Mary L. Arcila; Liliana Cadavid; Sonia Moreno; Gloria Garcia; Lucia Madrigal; Eric M. Reiman; Mauricio Arcos-Burgos; Gabriel Bedoya; Mary E. Brunkow; Gustavo Glusman; Jared C. Roach; Leroy Hood; Kenneth S. Kosik; Francisco Lopera

doi:10.1016/j.jalz.2013.09.005

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

Matthew A. Lalli, Hannah C. Cox, Mary L. Arcila, Liliana Cadavid, Sonia Moreno, Gloria Garcia, Lucia Madrigal, Eric M. Reiman, Mauricio Arcos-Burgos, Gabriel Bedoya, Mary E. Brunkow, Gustavo Glusman, Jared C. Roach, Leroy Hood, Kenneth S. Kosik, Francisco Lopera

Research output: Contribution to journal › Article › peer-review

32 Scopus citations

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.

Original language	English
Pages (from-to)	S277-S283.e10
Journal	Alzheimer's and Dementia
Volume	10
Issue number	5
DOIs	https://doi.org/10.1016/j.jalz.2013.09.005
State	Published - 1 Oct 2014
Externally published	Yes

Keywords

Alzheimer's disease
PSEN1
population genetics
whole-genome sequencing

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Lalli, M. A., Cox, H. C., Arcila, M. L., Cadavid, L., Moreno, S., Garcia, G., Madrigal, L., Reiman, E. M., Arcos-Burgos, M., Bedoya, G., Brunkow, M. E., Glusman, G., Roach, J. C., Hood, L., Kosik, K. S., & Lopera, F. (2014). Origin of the PSEN1 E280A mutation causing early-onset Alzheimer's disease. Alzheimer's and Dementia, 10(5), S277-S283.e10. https://doi.org/10.1016/j.jalz.2013.09.005

@article{39692917e69c4fa58f635743a30a4dfe,

title = "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",

author = "Lalli, {Matthew A.} and Cox, {Hannah C.} and Arcila, {Mary L.} and Liliana Cadavid and Sonia Moreno and Gloria Garcia and Lucia Madrigal and Reiman, {Eric M.} and Mauricio Arcos-Burgos and Gabriel Bedoya and Brunkow, {Mary E.} and Gustavo Glusman and Roach, {Jared C.} and Leroy Hood and Kosik, {Kenneth S.} and Francisco Lopera",

note = "Funding Information: Support for this work came from a National Institutes of Health Fogarty grant ( R01 AG029802 ; K.S.K.), the Errett Fisher Foundation (K.S.K.), and the University of Luxembourg–Institute for Systems Biology Program, Colciencias (grants 111540820543 and 111540820512 ; F.L.). The funding sources had no role in the data collection, data analysis, data interpretation, or writing of the report. K.S.K. had access to all the data in the study and had final responsibility for the decision to submit for publication. We extend our gratitude to our research subjects and other members of the PSEN1 E280A mutation kindred for their participation. Publisher Copyright: {\textcopyright} 2014 The Alzheimer's Association.",

year = "2014",

month = oct,

day = "1",

doi = "10.1016/j.jalz.2013.09.005",

language = "English",

volume = "10",

pages = "S277--S283.e10",

journal = "Alzheimer's and Dementia",

issn = "1552-5260",

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Lalli, MA, Cox, HC, Arcila, ML, Cadavid, L, Moreno, S, Garcia, G, Madrigal, L, Reiman, EM, Arcos-Burgos, M, Bedoya, G, Brunkow, ME, Glusman, G, Roach, JC, Hood, L, Kosik, KS & Lopera, F 2014, 'Origin of the PSEN1 E280A mutation causing early-onset Alzheimer's disease', Alzheimer's and Dementia, vol. 10, no. 5, pp. S277-S283.e10. https://doi.org/10.1016/j.jalz.2013.09.005

TY - JOUR

T1 - Origin of the PSEN1 E280A mutation causing early-onset Alzheimer's disease

AU - Lalli, Matthew A.

AU - Cox, Hannah C.

AU - Arcila, Mary L.

AU - Cadavid, Liliana

AU - Moreno, Sonia

AU - Garcia, Gloria

AU - Madrigal, Lucia

AU - Reiman, Eric M.

AU - Arcos-Burgos, Mauricio

AU - Bedoya, Gabriel

AU - Brunkow, Mary E.

AU - Glusman, Gustavo

AU - Roach, Jared C.

AU - Hood, Leroy

AU - Kosik, Kenneth S.

AU - Lopera, Francisco

N1 - Funding Information: Support for this work came from a National Institutes of Health Fogarty grant ( R01 AG029802 ; K.S.K.), the Errett Fisher Foundation (K.S.K.), and the University of Luxembourg–Institute for Systems Biology Program, Colciencias (grants 111540820543 and 111540820512 ; F.L.). The funding sources had no role in the data collection, data analysis, data interpretation, or writing of the report. K.S.K. had access to all the data in the study and had final responsibility for the decision to submit for publication. We extend our gratitude to our research subjects and other members of the PSEN1 E280A mutation kindred for their participation. Publisher Copyright: © 2014 The Alzheimer's Association.

PY - 2014/10/1

Y1 - 2014/10/1

N2 - 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.

AB - 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.

KW - Alzheimer's disease

KW - PSEN1

KW - population genetics

KW - whole-genome sequencing

UR - http://www.scopus.com/inward/record.url?scp=84908223294&partnerID=8YFLogxK

U2 - 10.1016/j.jalz.2013.09.005

DO - 10.1016/j.jalz.2013.09.005

M3 - Article

C2 - 24239249

AN - SCOPUS:84908223294

VL - 10

SP - S277-S283.e10

JO - Alzheimer's and Dementia

JF - Alzheimer's and Dementia

SN - 1552-5260

IS - 5

ER -

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

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Keywords

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