Variation of CAG repeats and two intragenic polymorphisms at SCA3 locus among Machado-Joseph disease/SCA3 patients and diverse normal populations from eastern India.
OBJECTIVE
MJD1/SCA3 is the most common type of spinocerebellar ataxia (SCA) worldwide. To explain the low prevalence of the disease among SCA patients from eastern India, we analysed CAG repeats and two bi-allelic intragenic markers at SCA3 locus among 412 normal individuals and 10 patients.


METHODS
For CAG repeat analysis, PCR amplified fragments were run on polyacrylamide gel, transferred to a membrane, probed with (CAG)10 and detected on an autoradiograph. Bi-allelic markers were analysed using allele specific PCR amplification.


RESULTS
Large normal alleles (>33 CAG repeats) were 0.015 in pooled populations. All the patients had the common haplotype C-A as observed worldwide. Frequency of C-A haplotype among large normal alleles was 0.75.


CONCLUSIONS
Observed low prevalence of SCA3 could be because of the low prevalence of large normal alleles that might act as the reservoir for the expanded alleles. SCA3 mutation in Indian populations had the same origin as found worldwide.
Chattopadhyay
B
B
Crystallography and Molecular Biology Division, Saha Institute of Nuclear Physics, Kolkata, India.
Basu
P
P
Gangopadhyay
P K
PK
Mukherjee
S C
SC
Sinha
K K
KK
Chakraborty
A
A
Roy
T
T
Roychoudhury
S
S
Majumder
P P
PP
Bhattacharyya
N P
NP
D000067699:Ataxin-3; D014644:Genetic Variation; D006801:Humans; D007194:India; D017827:Machado-Joseph Disease / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009687:Nuclear Proteins; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012097:Repressor Proteins; D012494:Sampling Studies; D018911:Trinucleotide Repeats
D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; C092341:ATXN3 protein, human; D000067699:Ataxin-3