Familial Mediterranean Fever In Lebanon: Founder Effects For Different MEFV Mutations

• Published in: Annals of human genetics Vol. 72; no. 1; pp. 41 - 47
• Main Authors: Jalkh, Nadine, Génin, Emmanuelle, Chouery, Eliane, Delague, Valérie, Medlej‐Hashim, Myrna, Idrac, Charles‐Antoine, Mégarbané, André, Serre, Jean‐Louis
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.01.2008
• Subjects: Alleles; Case-Control Studies; common ancestor; Familial Mediterranean Fever - genetics; Familial Mediterranean Fever - physiopathology; FMF; Founder Effect; Gene Frequency; Genetic Markers; haplotype; Haplotypes; Humans; Lebanon; Microsatellite Repeats; Mutation; Lebanon
• ISSN: 0003-4800; 1469-1809
• DOI: 10.1111/j.1469-1809.2007.00386.x

Summary Haplotype analysis of 376 Familial Mediterranean Fever (FMF) patients and 100 controls from Lebanon was performed using 4 microsatellite loci to study founder effects for the five most frequent mutations within the MEFV gene (M694V, M694I, V726A, M680I and E148Q). Each of these mutations was associated with a particular haplotype that was less frequent among controls, confirming that they have probably arisen from unique mutation events and that the carrier chromosomes derived from a common ancestor. The estimated ages of the most recent common ancestor for each of the 5 mutations, using the ESTIAGE program, were 7000, 8500, 15000, 23000 and 30000 years for M694V, M694I, V726A, M680I and E148Q, respectively. Varying the mutation rate at one of the markers led to younger age estimates, but the mutation E148Q remained the oldest one. Comparison of haplotype distributions among the different Lebanese religious groups confirmed that Muslim sub‐populations (Shiites and Sunnites) as well as Christian ones, including Armenians who were formerly settled in the South‐Eastern part of Asia Minor (Cilicia), are all derived from an ancient common ancestral population in which most of the MEFV mutations were already present with their respective associated haplotypes.