LRRK2
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- 作者：Cyrus P. Zabetian ; Carolyn M. Hutter ; Dora Yearout ; Alexis N. Lopez ; Stewart A. Factor ; Alida Griffith ; Berta C. Leis ; Thomas D. Bird ; John G. Nutt ; Donald S. Higgins ; John W. Roberts ; Denise M. Kay ; Karen L. Edwards ; Ali Samii ; Haydeh Payami
- 刊名：The American Journal of Human Genetics
- 出版年：2006
- 出版时间：October 2006
- 年：2006
- 卷：79
- 期：4
- 页码：752-758
- 全文大小：326 K
文摘
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.