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Pathogenic expansions of the SCA6 locus are associated with a common CACNA1A haplotype across the globe: founder effect or predisposing chromosome?

Pathogenic expansions of the SCA6 locus are associated with a common CACNA1A haplotype across the globe: founder effect or predisposing chromosome?
Pathogenic expansions of the SCA6 locus are associated with a common CACNA1A haplotype across the globe: founder effect or predisposing chromosome?
Spinocerebellar ataxia type 6 (SCA6) is a common cause of dominantly inherited ataxia due to an expansion of the CAG repeat in the CACNA1A gene. Affected individuals from the same population share a common haplotype, raising the possibility that most SCA6 cases have descended from a small number of common founders across the globe. To test this hypothesis, we carried out haplotype analysis on SCA6 families from Europe, South America and the Far East, including an established de novo SCA6 expansion. A core CACNA1A disease haplotype was found in affected individuals across the globe. This was also present in the unaffected father of the de novo case, suggesting that the shared chromosome predisposes to the CAG repeat expansion at the SCA6 locus. The SCA6 expansion lies within a CpG island, which could act as a cis-acting element predisposing to repeat expansion as for other CAG/CTG repeat diseases. Polymorphic variation in this region may explain the high-risk haplotype found in SCA6 families.
ataxia, spinocerebellar ataxia, trinucleotide repeat, founder effect, sca6, cacna1a
1018-4813
841-847
Craig, Kate
3eb35703-2b85-4625-b5ad-d2c62caed516
Takiyama, Yoshihisa
cacfea05-a1f4-4c21-8d70-d86992552b46
Soong, Bing-Wen
2df09545-66a7-41d8-a489-4bb83579e04f
Jardim, Laura B
58ae7520-33aa-4ede-89cc-75ec463724ec
Saraiva-Pereira, Maria Luiza
fc951672-514e-43c0-a42a-5e2afbe6b221
Lythgow, Kieren
ff7b3c7f-0c14-4f0a-b1cf-8ddcb6269dd7
Morino, Hiroyuki
e6a481c7-1d08-4712-9076-35d849a7d4af
Maruyama, Hirofumi
27b0dc8e-e903-4745-bfb3-84365dc03407
Kawakami, Hideshi
837b5dc8-3610-46fe-b923-adff1e0d9c98
Chinnery, Patrick F
87789d1a-5265-4815-9f11-194ed9b4ad94
Craig, Kate
3eb35703-2b85-4625-b5ad-d2c62caed516
Takiyama, Yoshihisa
cacfea05-a1f4-4c21-8d70-d86992552b46
Soong, Bing-Wen
2df09545-66a7-41d8-a489-4bb83579e04f
Jardim, Laura B
58ae7520-33aa-4ede-89cc-75ec463724ec
Saraiva-Pereira, Maria Luiza
fc951672-514e-43c0-a42a-5e2afbe6b221
Lythgow, Kieren
ff7b3c7f-0c14-4f0a-b1cf-8ddcb6269dd7
Morino, Hiroyuki
e6a481c7-1d08-4712-9076-35d849a7d4af
Maruyama, Hirofumi
27b0dc8e-e903-4745-bfb3-84365dc03407
Kawakami, Hideshi
837b5dc8-3610-46fe-b923-adff1e0d9c98
Chinnery, Patrick F
87789d1a-5265-4815-9f11-194ed9b4ad94

Craig, Kate, Takiyama, Yoshihisa, Soong, Bing-Wen, Jardim, Laura B, Saraiva-Pereira, Maria Luiza, Lythgow, Kieren, Morino, Hiroyuki, Maruyama, Hirofumi, Kawakami, Hideshi and Chinnery, Patrick F (2008) Pathogenic expansions of the SCA6 locus are associated with a common CACNA1A haplotype across the globe: founder effect or predisposing chromosome? European Journal of Human Genetics, 16 (7), 841-847. (doi:10.1038/ejhg.2008.20). (PMID:18285829)

Record type: Article

Abstract

Spinocerebellar ataxia type 6 (SCA6) is a common cause of dominantly inherited ataxia due to an expansion of the CAG repeat in the CACNA1A gene. Affected individuals from the same population share a common haplotype, raising the possibility that most SCA6 cases have descended from a small number of common founders across the globe. To test this hypothesis, we carried out haplotype analysis on SCA6 families from Europe, South America and the Far East, including an established de novo SCA6 expansion. A core CACNA1A disease haplotype was found in affected individuals across the globe. This was also present in the unaffected father of the de novo case, suggesting that the shared chromosome predisposes to the CAG repeat expansion at the SCA6 locus. The SCA6 expansion lies within a CpG island, which could act as a cis-acting element predisposing to repeat expansion as for other CAG/CTG repeat diseases. Polymorphic variation in this region may explain the high-risk haplotype found in SCA6 families.

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More information

Published date: 20 February 2008
Keywords: ataxia, spinocerebellar ataxia, trinucleotide repeat, founder effect, sca6, cacna1a

Identifiers

Local EPrints ID: 192205
URI: http://eprints.soton.ac.uk/id/eprint/192205
ISSN: 1018-4813
PURE UUID: bf916f85-05a4-46ac-aea7-f1262d320620

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Date deposited: 30 Jun 2011 12:44
Last modified: 08 Nov 2021 19:23

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Contributors

Author: Kate Craig
Author: Yoshihisa Takiyama
Author: Bing-Wen Soong
Author: Laura B Jardim
Author: Maria Luiza Saraiva-Pereira
Author: Kieren Lythgow
Author: Hiroyuki Morino
Author: Hirofumi Maruyama
Author: Hideshi Kawakami
Author: Patrick F Chinnery

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