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.
Laboratoire de Génétique Moléculaire des Eucaryotes du CNRS, Unité 184 de Biologie Moléculaire Génie Génétique de l'INSERM, Strasbourg, France.
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G
Sirugo
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B
Keats
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Fujita
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F
Duclos
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Purohit
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Koenig
J L
JL
Mandel
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