University of Oulu

HTT haplogroups in Finnish patients with Huntington disease. Susanna Ylönen, Jussi O.T. Sipilä, Marja Hietala, Kari Majamaa. Neurol Genet Jun 2019, 5 (3) e334; DOI: 10.1212/NXG.0000000000000334

HTT haplogroups in Finnish patients with Huntington disease

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Author: Ylönen, Susanna1,2; Sipilä, Jussi O.T.3,4,5; Hietala, Marja6,7;
Organizations: 1Division of Clinical Neuroscience, Neurology, University of Oulu
2Department of Neurology and Medical Research Center, Oulu University Hospital
3Department of Neurology, North Karelia Central Hospital, Siun Sote, Joensuu
4Division of Clinical Neurosciences, Turku University Hospital
5Neurology,,University of Turku
6Department of Clinical Genetics, Turku University Hospital
7Institute of Biomedicine, University of Turku, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 0.3 MB)
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Language: English
Published: Wolters Kluwer, 2019
Publish Date: 2020-04-09


Objective: To study genetic causes of the low frequency of Huntington disease (HD) in the Finnish population, we determined HTT haplogroups in the population and patients with HD and analyzed intergenerational Cytosine-Adenosine-Guanosine (CAG) stability.

Methods: A national cohort of patients with HD was used to identify families with mutant HTT (mHTT). HTT haplogroups were determined in 225 archival samples from patients and from 292 population samples. CAG repeats were phased with HTT haplotypes using data from parent-offspring pairs and other mHTT carriers in the family.

Results: The allele frequencies of HTT haplotypes in the Finnish population differed from those in 411 non-Finnish European subjects (p < 0.00001). The frequency of haplogroup A was lower than that in Europeans and haplogroup C was higher. Haplogroup A alleles were significantly more common in patients than in controls. Among patients with HD haplotypes A1 and A2 were more frequent than among the controls (p = 0.003). The mean size of the CAG repeat change was +1.38 units in paternal transmissions being larger than that (−0.17) in maternal transmissions (p = 0.008). CAG repeats on haplogroup A increased by 3.18 CAG units in paternal transmissions, but only by 0.11 units in maternal transmissions (p = 0.008), whereas haplogroup C repeat lengths decreased in both paternal and maternal transmissions.

Conclusions: The low frequency of HD in Finland is partly explained by the low frequency of the HD-associated haplogroup A in the Finnish population. There were remarkable differences in intergenerational CAG repeat dynamics that depended on HTT haplotype and parent gender.

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Series: Neurology. Genetics
ISSN: 2376-7839
ISSN-E: 2376-7839
ISSN-L: 2376-7839
Volume: 5
Issue: 3
Article number: UNSP e334
DOI: 10.1212/NXG.0000000000000334
Type of Publication: A1 Journal article – refereed
Field of Science: 3124 Neurology and psychiatry
3111 Biomedicine
Funding: This study was supported in part by grants from the Sigrid Juselius Foundation, Turku University Foundation, and the Finnish Parkinson Foundation.
Copyright information: © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.