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

Academic Article

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. © 2006 by The American Society of Human Genetics. All rights reserved.
  • Authors

    Published In

    Digital Object Identifier (doi)

    Author List

  • Zabetian CP; Hutter CM; Yearout D; Lopez AN; Factor SA; Griffith A; Leis BC; Bird TD; Nutt JG; Higgins DS
  • Start Page

  • 752
  • End Page

  • 758
  • Volume

  • 79
  • Issue

  • 4