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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
DNA haplotype analysis of huntington disease reveals clues to the origins and mechanisms of CAG expansion and reasons for geographic variations of prevalence
Human Molecular Genetics, Volume 3, No. 12, Year 1994
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Description
This study of allelic association using three Intra- and two extragenlc markers within 150 kb of the Huntlngton disease (HD) mutation has provided evidence for linkage disequilibrium for four of five markers. Haplotype analysis of 67 HD families using markers in strong linkage disequilibrium with HD Identified two haplotypes underlying 77.6% of HD chromosomes. Normal chromosomes with these two haplotypes had a mean number of CAG repeats significantly larger than and an altered distribution of CAG repeats compared with other normal chromosomes. Furthermore, haplotype analysis of five new mutation families reveals that HD has arisen on these same two chromosomal haplotypes. These findings suggest that HD arises more frequently on chromosomes with specific DNA haplotypes and higher CAG repeat lengths. We then studied CAG and CCG repeat lengths In the HD gene on 896 control chromosomes from different ancestries to determine whether the markedly reduced frequency of HD in Finland, Japan, China and African Blacks Is associated with an altered frequency of DNA haplotypes and subsequently lower CAG lengths on control chromosomes compared to populations of Western European descent. The results show a highly significant positive correlation between CAG size on normal chromosomes and the frequency of HD and a significant inverse relationship between CAG and CCG repeat lengths. In populations with lowered prevalence rates of HD, CAG repeat lengths are smaller and the distribution of CCG alleles Is markedly different from Western European populations. These findings suggest that, in addition to European emigration, new mutations make a contribution to geographical variation of prevalence rates and is consistent with a multistep model of HD developing from normal chromosomes with higher CAG repeat lengths. © 1994 Oxford University Press.
Authors & Co-Authors
Squitieri, Ferdinando
Canada, Vancouver
The University of British Columbia
Andrew, S. E.
Canada, Vancouver
The University of British Columbia
Goldberg, Y. P.
Canada, Vancouver
The University of British Columbia
Kremer, Berry P.H.
Canada, Vancouver
The University of British Columbia
Netherlands, Nijmegen
Radboud University Medical Center
Spence, N.
Canada, Vancouver
The University of British Columbia
Zelsler, J.
Canada, Vancouver
The University of British Columbia
Nichol, K.
Canada, Vancouver
The University of British Columbia
Theilmann, J.
Canada, Vancouver
The University of British Columbia
Greenberg, Jacquie L.
South Africa, Cape Town
University of Cape Town
Goto, J.
Japan, Tokyo
The University of Tokyo
Kanazawa, I.
Japan, Tokyo
The University of Tokyo
Vesa, J.
Finland, Helsinki
Terveyden ja Hyvinvoinnin Laitos
Peltonen-Palotie, Leena Johanna
Finland, Helsinki
Terveyden ja Hyvinvoinnin Laitos
Almqvist, Elisabeth Winnberg
Sweden, Stockholm
Karolinska Universitetssjukhuset
Sweden, Stockholm
Karolinska Institutet
Anvret, M.
Sweden, Stockholm
Karolinska Institutet
Telenius, Håkan
Canada, Vancouver
The University of British Columbia
Lin, B.
Canada, Vancouver
The University of British Columbia
Napolitano, G.
Italy, Naples
Università Degli Studi Di Napoli Federico Ii
Morgan, Kenneth
Canada, Montreal
Université Mcgill
Hayden, Michael R.
Canada, Vancouver
The University of British Columbia
Statistics
Citations: 182
Authors: 20
Affiliations: 9
Identifiers
Doi:
10.1093/hmg/3.12.2103
ISSN:
09646906
Research Areas
Cancer
Genetics And Genomics
Study Design
Cross Sectional Study