Document Detail

Single sperm analysis of the CAG repeats in the gene for Machado-Joseph disease (MJD1): evidence for non-Mendelian transmission of the MJD1 gene and for the effect of the intragenic CGG/GGG polymorphism on the intergenerational instability.
MedLine Citation:
PMID:  9215676     Owner:  NLM     Status:  MEDLINE    
To investigate the mechanism of the meiotic instability of expanded CAG repeats in the gene for Machado-Joseph disease (MJD1), we analyzed the CAG repeat sizes of 1036 single sperm from six individuals with Machado-Joseph disease (MJD). The segregation ratio between single sperm with an expanded allele and those with a normal allele is significantly different (P <0.0001) from the expected 1:1 segregation ratio, which demonstrates segregation distortion of expanded alleles in male meiosis. In single sperm from individuals with the [expanded (CAG)n-CGG]/[normal (CAG)n-GGG] genotype, significantly greater instability of the CAG repeat was observed compared with single sperm from individuals with the [expanded (CAG)n-CGG]/[normal (CAG)n-CGG] genotype (F-test, P <0.001). These findings in single sperm confirm non-Mendelian transmission of the MJD1 gene and the effect of the intragenic CGG/GGG polymorphism on the intergenerational instability of the CAG repeats in the MJD1 gene, which have been observed in clinical and genetic studies. Our results indicate similarities and dissimilarities between MJD and Huntington's disease or myotonic dystrophy in terms of the inter-allelic interaction, segregation distortions and size distribution of trinucleotide repeats in mutant alleles. Further study is required to determine whether there is a common mechanism underlying the instability of the triplet repeats in 'triplet repeat diseases'.
Y Takiyama; K Sakoe; M Soutome; M Namekawa; T Ogawa; I Nakano; S Igarashi; M Oyake; H Tanaka; S Tsuji; M Nishizawa
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Human molecular genetics     Volume:  6     ISSN:  0964-6906     ISO Abbreviation:  Hum. Mol. Genet.     Publication Date:  1997 Jul 
Date Detail:
Created Date:  1997-08-28     Completed Date:  1997-08-28     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9208958     Medline TA:  Hum Mol Genet     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  1063-8     Citation Subset:  IM    
Department of Neurology, Jichi Medical School, Minamikawachi, Tochigi, Japan.
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MeSH Terms
Gene Frequency
Leukocytes / physiology
Machado-Joseph Disease / genetics*
Nerve Tissue Proteins / genetics*
Nuclear Proteins
Polymorphism, Genetic*
Repressor Proteins
Spermatozoa / physiology*
Trinucleotide Repeats*
Reg. No./Substance:
0/Nerve Tissue Proteins; 0/Nuclear Proteins; 0/Repressor Proteins; EC 3.4.22.-/ATXN3 protein, human

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