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
Neuroscience Research Institute, Department of Molecular Cellular Developmental Biology, University of California, Santa Barbara, CA, USA.
Institute for Systems Biology, Seattle, WA, USA.
Alzheimers Dement. 2014 Oct;10(5 Suppl):S277-S283.e10. doi: 10.1016/j.jalz.2013.09.005. Epub 2013 Nov 13.
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.
早老素1（E280A）突变导致早发性阿尔茨海默病。了解该突变的起源将为医学遗传学提供信息。
我们对来自哥伦比亚安蒂奥基亚的102个人的基因组进行了测序。我们应用同源性分析来确定共同祖先区域。我们估计了E280A突变的年龄以及携带该突变的单倍型的本地祖先。
所有受影响个体共享一个包含E280A的1.8 Mb最小单倍型。我们估计E280A最近共同祖先的时间为10代（95%可信区间，7.2 - 12.6）。我们将新发突变事件追溯到15代（95%可信区间，11 - 25）之前。我们推断共享单倍型的地理起源为西欧。
E280A的年龄和地理起源与一个单一奠基者一致，该奠基者可追溯到16世纪初开始殖民哥伦比亚的西班牙征服者时期。
