Copyright © 2006 The American Society of Human Genetics. All rights reserved.
The American Journal of Human Genetics, Volume 79, Issue 4, 752-758, 1 October 2006
doi:10.1086/508025
Report
LRRK2 G2019S in Families with Parkinson Disease Who Originated from Europe and the Middle East: Evidence of Two Distinct Founding Events Beginning Two Millennia Ago
Cyrus P. Zabetiana, c, 
, 
, Carolyn M. Hutterd, Dora Yearouta, c, Alexis N. Lopeza, c, Stewart A. Factor*, f, Alida Griffithh, Berta C. Leish, Thomas D. Birda, c, John G. Nutti, Donald S. Higginsf, John W. Robertse, Denise M. Kayg, Karen L. Edwardsd, Ali Samiib, c and Haydeh Payamig
a Geriatric Research Education and Clinical Center, Seattle
b Parkinson's Disease Research Education and Clinical Center, Seattle
c Veterans Affairs Puget Sound Health Care System, Department of Neurology, University of Washington School of Medicine, Seattle
d Department of Epidemiology, University of Washington School of Public Health and Community Medicine, Seattle
e Virginia Mason Medical Center, Seattle
f Parkinson’s Disease and Movement Disorder Clinic, Albany Medical Center, Albany
g Genomics Institute, Wadsworth Center, New York State Department of Health, Albany
h Booth Gardner Parkinson’s Care Center, Evergreen Hospital Medical Center, Kirkland, WA
i Department of Neurology, Oregon Health and Science University, Portland
Address for correspondence and reprints: Dr. Cyrus P. Zabetian, Geriatric Research Education and Clinical Center S-182, Veterans Affairs Puget Sound Health Care System, 1660 South Columbian Way, Seattle, WA 98108* Present affiliation: Department of Neurology, Emory University School of Medicine, Atlanta.
Abstract
The leucine-rich repeat kinase 2 (LRRK2) G2019S mutation is the most common genetic determinant of Parkinson disease (PD) identified to date. It accounts for 1%–7% of PD in patients of European origin and 20%–40% in Ashkenazi Jews and North African Arabs with PD. Previous studies concluded that patients from these populations all shared a common Middle Eastern founder who lived in the 13th century. We tested this hypothesis by genotyping 25 microsatellite and single-nucleotide–polymorphism markers in 22 families with G2019S and observed two distinct haplotypes. Haplotype 1 was present in 19 families of Ashkenazi Jewish and European ancestry, whereas haplotype 2 occurred in three European American families. Using a maximum-likelihood method, we estimated that the families with haplotype 1 shared a common ancestor 2,250 (95% confidence interval 1,650–3,120) years ago, whereas those with haplotype 2 appeared to share a more recent founder. Our data suggest two separate founding events for G2019S in these populations, beginning at a time that coincides with the Jewish Diasporas.
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