Strong linkage disequilibrium and haplotype analysis in Japanese pedigrees with Machado-Joseph disease.
To identify the markers tightly linked to Machado-Joseph disease (MJD) and to investigate whether a limited number of ancestral chromosomes are shared by Japanese MJD pedigrees, a detailed linkage analysis employing D14S55, D14S48, D14S67, D14S291, D14S280, AFM343vf1, D14S81, D14S265, D14S62, and D14S65 was performed. The results of multipoint linkage analysis as well as detection of critical recombination events indicate that the gene for MJD is localized in a 4-cM region between D14S280-D14S81. We found strong linkage disequilibria at AFM343vf1 and D14S81, and association of a few common haplotypes with MJD. These results indicate that there is an obvious founder effect in Japanese MJD and suggest the possibility of the existence of predisposing haplotypes which are prone to expansions of CAG repeats.
Endo
K
K
Department of Neurology, Clinical Neuroscience Branch, Brain Research Institute, Niigata University, Japan.
Sasaki
H
H
Wakisaka
A
A
Tanaka
H
H
Saito
M
M
Igarashi
S
S
Takiyama
Y
Y
Sanpei
K
K
Iwabuchi
K
K
Suzuki
Y
Y
Onari
K
K
Suzuki
T
T
Weissenbach
J
J
Weber
J L
JL
Nomura
Y
Y
Segawa
M
M
Nishizawa
M
M
Tsuji
S
S
D000067699:Ataxin-3; D002874:Chromosome Mapping; D002883:Chromosomes, Human, Pair 14; D005260:Female; D005819:Genetic Markers; D005843:Geography; D006239:Haplotypes; D006801:Humans; D007564:Japan / Q000453:epidemiology; D015810:Linkage Disequilibrium; D017827:Machado-Joseph Disease / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D018895:Microsatellite Repeats; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D010375:Pedigree; D011506:Proteins / Q000235:genetics; D012097:Repressor Proteins
D005819:Genetic Markers; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D011506:Proteins; D012097:Repressor Proteins; C092341:ATXN3 protein, human; D000067699:Ataxin-3