title: 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.
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.
authors.affiliation: Geriatric Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA 98108, USA. zabetian@u.washington.edu
authors.forename: Cyrus P
authors.initials: CP
authors.lastname: Zabetian
authors.forename: Carolyn M
authors.initials: CM
authors.lastname: Hutter
authors.forename: Dora
authors.initials: D
authors.lastname: Yearout
authors.forename: Alexis N
authors.initials: AN
authors.lastname: Lopez
authors.forename: Stewart A
authors.initials: SA
authors.lastname: Factor
authors.forename: Alida
authors.initials: A
authors.lastname: Griffith
authors.forename: Berta C
authors.initials: BC
authors.lastname: Leis
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Bird
authors.forename: John G
authors.initials: JG
authors.lastname: Nutt
authors.forename: Donald S
authors.initials: DS
authors.lastname: Higgins
authors.forename: John W
authors.initials: JW
authors.lastname: Roberts
authors.forename: Denise M
authors.initials: DM
authors.lastname: Kay
authors.forename: Karen L
authors.initials: KL
authors.lastname: Edwards
authors.forename: Ali
authors.initials: A
authors.lastname: Samii
authors.forename: Haydeh
authors.initials: H
authors.lastname: Payami
mesh_terms: D000352:Africa, Northern; D019943:Amino Acid Substitution; D016022:Case-Control Studies; D005190:Family; D005260:Female; D006239:Haplotypes; D006801:Humans; D007585:Jews / Q000235:genetics*; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008297:Male; D008877:Middle East; D010300:Parkinson Disease / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012984:Software; D044465:White People / Q000235:genetics*
chemical_list: C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases