Friedreich ataxia in Louisiana Acadians: demonstration of a founder effect by analysis of microsatellite-generated extended haplotypes.
Eleven Acadian families with Friedreich ataxia (FA) who were from southwest Louisiana were studied with a series of polymorphic markers spanning 310 kb in the D9S5-D9S15 region previously shown to be tightly linked to the disease locus. In particular, three very informative microsatellites were tested. Evidence for a strong founder effect was found, since a specific extended haplotype spanning 230 kb from 26P (D9S5) to MCT112 (D9S15) was present on 70% of independent FA chromosomes and only once (6%) on the normal ones. There was no evident correlation between haplotypes and clinical expression. The typing of an additional microsatellite (GS4) located 80 kb from MCT112 created a divergence of the main FA-linked haplotype, generating four minor and one major haplotype. A similar split was observed with GS4 in a patient homozygous for a rare 26P-to-MCT112 haplotype. These results suggest that GS4 is flanking marker for the disease locus, although other interpretations are possible.
Sirugo
G
G
Laboratoire de Génétique Moléculaire des Eucaryotes du CNRS, Unité 184 de Biologie Moléculaire Génie Génétique de l'INSERM, Strasbourg, France.
Keats
B
B
Fujita
R
R
Duclos
F
F
Purohit
K
K
Koenig
M
M
Mandel
J L
JL
D000293:Adolescent; D002648:Child; D003241:Consanguinity; D004276:DNA, Satellite / Q000235:genetics*; D005260:Female; D005621:Friedreich Ataxia / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics*; D008040:Genetic Linkage; D005819:Genetic Markers; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D008145:Louisiana / Q000453:epidemiology; D008297:Male; D010375:Pedigree; D011110:Polymorphism, Genetic / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D011792:Quebec / Q000208:ethnology; D011995:Recombination, Genetic
D004276:DNA, Satellite; D005819:Genetic Markers