Matthew A Lalli1, Hannah C Cox2, Mary L Arcila1, Liliana Cadavid3, Sonia Moreno3, Gloria Garcia3, Lucia Madrigal3, Eric M Reiman4, Mauricio Arcos-Burgos5, Gabriel Bedoya6, Mary E Brunkow2, Gustavo Glusman2, Jared C Roach2, Leroy Hood2, Kenneth S Kosik7, Francisco Lopera3. 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.
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.
Authors: Yael Baran; Bogdan Pasaniuc; Sriram Sankararaman; Dara G Torgerson; Christopher Gignoux; Celeste Eng; William Rodriguez-Cintron; Rocio Chapela; Jean G Ford; Pedro C Avila; Jose Rodriguez-Santana; Esteban Gonzàlez Burchard; Eran Halperin Journal: Bioinformatics Date: 2012-04-11 Impact factor: 6.937
Authors: Katarzyna Bryc; Christopher Velez; Tatiana Karafet; Andres Moreno-Estrada; Andy Reynolds; Adam Auton; Michael Hammer; Carlos D Bustamante; Harry Ostrer Journal: Proc Natl Acad Sci U S A Date: 2010-05-05 Impact factor: 11.205
Authors: Matthew A Lalli; Gloria Garcia; Lucia Madrigal; Mauricio Arcos-Burgos; Mary Luz Arcila; Kenneth S Kosik; Francisco Lopera Journal: Hum Mutat Date: 2012-08-10 Impact factor: 4.878
Authors: Radoje Drmanac; Andrew B Sparks; Matthew J Callow; Aaron L Halpern; Norman L Burns; Bahram G Kermani; Paolo Carnevali; Igor Nazarenko; Geoffrey B Nilsen; George Yeung; Fredrik Dahl; Andres Fernandez; Bryan Staker; Krishna P Pant; Jonathan Baccash; Adam P Borcherding; Anushka Brownley; Ryan Cedeno; Linsu Chen; Dan Chernikoff; Alex Cheung; Razvan Chirita; Benjamin Curson; Jessica C Ebert; Coleen R Hacker; Robert Hartlage; Brian Hauser; Steve Huang; Yuan Jiang; Vitali Karpinchyk; Mark Koenig; Calvin Kong; Tom Landers; Catherine Le; Jia Liu; Celeste E McBride; Matt Morenzoni; Robert E Morey; Karl Mutch; Helena Perazich; Kimberly Perry; Brock A Peters; Joe Peterson; Charit L Pethiyagoda; Kaliprasad Pothuraju; Claudia Richter; Abraham M Rosenbaum; Shaunak Roy; Jay Shafto; Uladzislau Sharanhovich; Karen W Shannon; Conrad G Sheppy; Michel Sun; Joseph V Thakuria; Anne Tran; Dylan Vu; Alexander Wait Zaranek; Xiaodi Wu; Snezana Drmanac; Arnold R Oliphant; William C Banyai; Bruce Martin; Dennis G Ballinger; George M Church; Clifford A Reid Journal: Science Date: 2009-11-05 Impact factor: 47.728
Authors: Joshua Mark Galanter; Juan Carlos Fernandez-Lopez; Christopher R Gignoux; Jill Barnholtz-Sloan; Ceres Fernandez-Rozadilla; Marc Via; Alfredo Hidalgo-Miranda; Alejandra V Contreras; Laura Uribe Figueroa; Paola Raska; Gerardo Jimenez-Sanchez; Irma Silva Zolezzi; Maria Torres; Clara Ruiz Ponte; Yarimar Ruiz; Antonio Salas; Elizabeth Nguyen; Celeste Eng; Lisbeth Borjas; William Zabala; Guillermo Barreto; Fernando Rondón González; Adriana Ibarra; Patricia Taboada; Liliana Porras; Fabián Moreno; Abigail Bigham; Gerardo Gutierrez; Tom Brutsaert; Fabiola León-Velarde; Lorna G Moore; Enrique Vargas; Miguel Cruz; Jorge Escobedo; José Rodriguez-Santana; William Rodriguez-Cintrón; Rocio Chapela; Jean G Ford; Carlos Bustamante; Daniela Seminara; Mark Shriver; Elad Ziv; Esteban Gonzalez Burchard; Robert Haile; Esteban Parra; Angel Carracedo Journal: PLoS Genet Date: 2012-03-08 Impact factor: 5.917
Authors: Goncalo R Abecasis; Adam Auton; Lisa D Brooks; Mark A DePristo; Richard M Durbin; Robert E Handsaker; Hyun Min Kang; Gabor T Marth; Gil A McVean Journal: Nature Date: 2012-11-01 Impact factor: 49.962
Authors: Kenneth S Kosik; Claudia Muñoz; Liliana Lopez; Mary Luz Arcila; Gloria García; Lucía Madrigal; Sonia Moreno; Silvia Ríos Romenets; Hugo Lopez; Madelyn Gutierrez; Jessica B Langbaum; William Cho; Shehnaaz Suliman; Pierre N Tariot; Carole Ho; Eric M Reiman; Francisco Lopera Journal: Neurology Date: 2014-12-03 Impact factor: 9.910
Authors: Laura Ramirez Aguilar; Juliana Acosta-Uribe; Margarita M Giraldo; Sonia Moreno; Ana Baena; Diana Alzate; Rosario Cuastumal; David Aguillón; Lucía Madrigal; Amanda Saldarriaga; Alexander Navarro; Gloria P Garcia; Daniel C Aguirre-Acevedo; Ethan G Geier; J Nicholas Cochran; Yakeel T Quiroz; Richard M Myers; Jennifer S Yokoyama; Kenneth S Kosik; Francisco Lopera Journal: Alzheimers Dement Date: 2019-02-10 Impact factor: 21.566
Authors: Irving E Vega; Laura Y Cabrera; Cassandra M Wygant; Daniel Velez-Ortiz; Scott E Counts Journal: J Alzheimers Dis Date: 2017 Impact factor: 4.472
Authors: Viviana Soto-Mercado; Miguel Mendivil-Perez; Carlos Velez-Pardo; Francisco Lopera; Marlene Jimenez-Del-Rio Journal: PLoS One Date: 2020-05-21 Impact factor: 3.240
Authors: John Darrell Van Horn; Andrei Irimia; Carinna M Torgerson; Avnish Bhattrai; Zachary Jacokes; Paul M Vespa Journal: J Neurosci Res Date: 2017-05-20 Impact factor: 4.164
Authors: Jorge J Llibre-Guerra; Yan Li; Ricardo F Allegri; Patricio Chrem Mendez; Ezequiel I Surace; Juan J Llibre-Rodriguez; Ana Luisa Sosa; Carmen Aláez-Verson; Erika-Mariana Longoria; Alberto Tellez; Karol Carrillo-Sánchez; Luis Leonardo Flores-Lagunes; Victor Sánchez; Leonel Tadao Takada; Ricardo Nitrini; Norberto Anizio Ferreira-Frota; Joyce Benevides-Lima; Francisco Lopera; Laura Ramírez; Ivonne Jiménez-Velázquez; Christian Schenk; Daisy Acosta; María Isabel Behrens; Michelle Doering; Ellen Ziegemeier; John C Morris; Eric McDade; Randall J Bateman Journal: Alzheimers Dement Date: 2020-11-23 Impact factor: 21.566