Abstract
This study was planned to determine the number of origins of the mutation underlying Huntington's disease (HD) in Sweden. Haplotypes were constructed for 23 different HD families, using six different polymorphisms [(CCG) n , GT70, 674, BS1, E2 and 4.2], including two within the gene. In addition, extensive genealogical investigations were performed, and the geographical origin of the haplotypes was studied. Ten different haplotypes were observed suggesting multiple origins for the HD mutation in Sweden. Analysis of the two polymorphic markers within the HD gene (the CCG repeat and GT70) indicates that there are at least three origins for the HD mutation in Sweden. One of these haplotypes (7/A) accounts for 89% of the families, suggesting that the majority of the Swedish HD families are related through a single HD mutation of ancient origin. Furthermore, three of the families that were previously considered to be unrelated could be traced to a common ancestor in the 15th century, a finding that is consistent with this hypothesis.
This is a preview of subscription content, log in via an institution to check access.
Access this article
We’re sorry, something doesn't seem to be working properly.
Please try refreshing the page. If that doesn't work, please contact support so we can address the problem.
Similar content being viewed by others
References
Andrew S, Theilmann J, Hedrick A, Mah D, Weber B, Hayden MR (1992) Nonrandom association between Huntington disease and two loci separated by about 3 Mb on 4p16. 3. Genomics 13:301–311
Andrew S, Goldberg YP, Kremer B, Telenius H, Theilmann J, Adam S, Starr E, Squitieri F, Lin B, Kalchman MA, Graham RK, Hayden MR (1993 a) The relationship between trinucleotide (CAG) repeat length and clinical features of Huntington's disease. Nature Genet 4:398–403
Andrew S, Theilmann J, Almqvist E, Norremolle A, Lucotte G, Anvret M, Sorensen SA, Turpin JC, Hayden MR (1993 b) DNA analysis of distinct populations suggests multiple origins for the mutation causing Huntington disease. Clin Genet 43:286–294
Andrew SE, Goldberg YP, Kremer B, Squitieri F, Theilmann J, Zeisler J, Telenius H, Adam S, Almqvist E, Anvret M, Lucotte G, Stoessl AJ, Campanella G, Hayden MR (1994 a) Huntington disease without CAG expansion: true phenocopies or errors in assignment? Am J Hum Genet 54:852–863
Andrew SE, Goldberg YP, Theilmann J, Zeisler J, Hayden MR (1994 b) A CCG repeat polymorphism adjacent to the CAG repeat in the Huntington disease gene: implications for diagnostic accuracy and predictive testing. Hum Mol Genet 3:65–67
Duyao M, Ambrose C, Myers R, Novelletto A, Persichetti F, Frontali M, Folstein S, Ross C, Franz M, Abbott M, Gray J, Conneally P, Young A, Penney J, Hollingsworth Z, Shoulson I, Lazzarini A, Falek A, Koroshetz W, Sax D, Bird E, Vonsattel J, Bonilla E, Alvir J, Bickham Conde J, Cha J-H, Dure L, Gomez F, Ramos M, Sanchez-Ramos J, Snodgrass S, Young M de, Wexler N, Moscovitz C, Penchaszadeh G, MacFarlane H, Anderson M, Jenkins B, Srinidhi J, Barnes G, Gusella J, Mac-Donald M (1993) Trinucleotide repeat length instability and age of onset in Huntington's disease. Nature Genet 4:387–392
Goldberg YP, Andrew SE, Clarke LA, Hayden MR (1993 a) A PCR method for accurate assessment of trinucleotide repeat expansion in Huntington disease. Hum Mol Genet 2:635–636
Goldberg YP, Kremer SE, Andrew SE, Theilmann J, Graham RK, Squitieri F, Telenius H, Adam S, Sajoo A, Starr E, Heiberg A, Wolff G, Hayden MR (1993 b) Molecular analysis of new mutations for Huntington's disease: intermediate alleles and sex of origin effects. Nature Genet 5:174–179
Harper PS (1991) Huntington's disease. Saunders, Eondon
Hayden MR (1981) Huntington's chorea. Springer. Berlin Heidelberg New York
The Huntington's Disease Collaborative Research Group (1993) A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. Cell 72:971–983
Ikonen E, Ignatius J, Norio R, Palo J, Peltonen E (1992) Huntington's disease in Finland: a molecular and genealogical study. Hum Genet 89:275–280
Lin B, Rommens JM, Graham RK, Kalchman M, MacDonald H, Nasir J, Delaney A, Goldberg YP, Hayden MR (1993) Differential 3′ polyadenylation of the Huntington disease gene results in two mRNA species with variable tissue expression. Hum Mol Genet 2:1541–1545
MacDonald ME, Lin C, Srinidhi E, Bates G, Altherr M, Whaley WL, Lehrach H, Wasmuth J, Gusella JF (1991) Complex patterns of linkage disequilibrium in the Huntington disease region. Am J Hum Genet 49:723–734
MacDonald ME, Novelletto A, Lin C, Tagle D, Barnes G, Bates G, Taylor S, Allitto B, Altherr M, Myers R, Lehrach H, Collins FS, Wasmuth JJ, Frontali M, Gusella JF (1992) The Huntington's disease candidate region exhibits many different haplotypes. Nature Genet 1:99–103
Mattsson B (1974) Huntington's chorea in Sweden. Prevalence and genetic data. Acta Psychiatr Scand 225 (Suppl):211–216
Norremolle A, Riess O, Epplen JT, Fenger K, Hasholt L, Sorensen SA (1993) Trinucleotide repeat elongation in the huntingtin gene in Huntington disease patients from 71 Danish families. Hum Mol Genet 2:1475–1476
Palo J, Somer H, Ikonen E, Karila L, Peltonen L (1987) Eow prevalence of Huntington's disease in Finland. Eancet II:805–806
Rommens JM, Lin B, Hutchinson GB, Andrew SE, Goldberg YP, Glaves ML, Graham R, Lai V, McArthur J, Nasir J, Theilmann J, McDonald H, Kalchman M, Clarke LA, Hayden MR (1993) A transcription map of the region containing the Huntington disease gene. Hum Mol Genet 2:901–907
Rubinsztein DC, Barton DE, Davison BCC, Ferguson-Smith MA (1993) Analysis of the huntingtin gene reveals a trinucleotidelength polymorphism in the region of the gene that contains two CCG-rich stretches and a correlation between decreased age of onset of Huntington's disease and CAG repeat number. Hum Mol Genet 2:1713–1715
Sjögren T (1936) Vererbungsmedizinische Untersuchungen über Huntingtons chorea in einer schwedischen Bauernpopulation. Vererb Konstit Lehre 19:131–165
Snell RG, MacMillan JC, Cheadle JP, Fenton I, Eazarou LP, Davies P, MacDonald ME, Gusella JF, Harper PS, Shaw DJ (1993) Relationship between trinucleotide repeat expansion and phenotypic variation in Huntington's disease. Nature Genet 4:393–397
Stine OC, Pleasant N, Franz ME, Abbott MH, Folstein SE, Ross CA (1993) Correlation between the onset age of Huntington's disease and length of the trinucleotide repeat in IT-15. Hum Mol Genet 2:1547–1549
Weber B, Collins C, Kowbel D, Riess O, Hayden MR (1991) Identification of multiple CpG-islands and associated conserved sequences in a candidate region for the Huntington disease gene. enomics 11:1113–1124
Zühlke C, Riess O, Schröder K, Siedlaczck I, Epplen JT, Engel W, Thies U (1993) Expansion of the (CAG) n repeat causing Huntington's disease in 352 patients of German origin. Hum Mol Genet 2:1467–1469
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Almqvist, E., Andrew, S., Theilmann, J. et al. Geographical distribution of haplotypes in Swedish families with Huntington's disease. Hum Genet 94, 124–128 (1994). https://doi.org/10.1007/BF00202856
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00202856