Abstract
Creutzfeldt-Jakob disease (CJD) belongs to a group of prion diseases that may be infectious, sporadic, or hereditary. The 200K point mutation in the PRNP gene is the most frequent cause of hereditary CJD, accounting for >70% of families with CJD worldwide. Prevalence of the 200K variant of familial CJD is especially high in Slovakia, Chile, and Italy, and among populations of Libyan and Tunisian Jews. To study ancestral origins of the 200K mutation-associated chromosomes, we selected microsatellite markers flanking the PRNP gene on chromosome 20p12-pter and an intragenic single-nucleotide polymorphism at the PRNP codon 129. Haplotypes were constructed for 62 CJD families originating from 11 world populations. The results show that Libyan, Tunisian, Italian, Chilean, and Spanish families share a major haplotype, suggesting that the 200K mutation may have originated from a single mutational event, perhaps in Spain, and spread to all these populations with Sephardic migrants expelled from Spain in the Middle Ages. Slovakian families and a family of Polish origin show another unique haplotype. The haplotypes in families from Germany, Sicily, Austria, and Japan are different from the Mediterranean or eastern European haplotypes. On the basis of this study, we conclude that founder effect and independent mutational events are responsible for the current geographic distribution of hereditary CJD associated with the 200K mutation.
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- Bird A. P. DNA methylation and the frequency of CpG in animal DNA. Nucleic Acids Res. 1980 Apr 11;8(7):1499–1504. doi: 10.1093/nar/8.7.1499. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Brown P., Cathala F., Castaigne P., Gajdusek D. C. Creutzfeldt-Jakob disease: clinical analysis of a consecutive series of 230 neuropathologically verified cases. Ann Neurol. 1986 Nov;20(5):597–602. doi: 10.1002/ana.410200507. [DOI] [PubMed] [Google Scholar]
- Brown P., Gibbs C. J., Jr, Rodgers-Johnson P., Asher D. M., Sulima M. P., Bacote A., Goldfarb L. G., Gajdusek D. C. Human spongiform encephalopathy: the National Institutes of Health series of 300 cases of experimentally transmitted disease. Ann Neurol. 1994 May;35(5):513–529. doi: 10.1002/ana.410350504. [DOI] [PubMed] [Google Scholar]
- Brown P., Goldfarb L. G., Cathala F., Vrbovská A., Sulima M., Nieto A., Gibbs C. J., Jr, Gajdusek D. C. The molecular genetics of familial Creutzfeldt-Jakob disease in France. J Neurol Sci. 1991 Oct;105(2):240–246. doi: 10.1016/0022-510x(91)90151-v. [DOI] [PubMed] [Google Scholar]
- Brown P., Gálvez S., Goldfarb L. G., Nieto A., Cartier L., Gibbs C. J., Jr, Gajdusek D. C. Familial Creutzfeldt-Jakob disease in Chile is associated with the codon 200 mutation of the PRNP amyloid precursor gene on chromosome 20. J Neurol Sci. 1992 Oct;112(1-2):65–67. doi: 10.1016/0022-510x(92)90133-6. [DOI] [PubMed] [Google Scholar]
- Collinge J., Palmer M. S., Campbell T., Sidle K. C., Carroll D., Harding A. Inherited prion disease (PrP lysine 200) in Britain: two case reports. BMJ. 1993 Jan 30;306(6873):301–302. doi: 10.1136/bmj.306.6873.301. [DOI] [PMC free article] [PubMed] [Google Scholar]
- D'Alessandro M., Petraroli R., Ladogana A., Pocchiari M. High incidence of Creutzfeldt-Jakob disease in rural Calabria, Italy. Lancet. 1998 Dec 19;352(9145):1989–1990. doi: 10.1016/S0140-6736(05)61335-9. [DOI] [PubMed] [Google Scholar]
- Gabizon R., Rosenmann H., Meiner Z., Kahana I., Kahana E., Shugart Y., Ott J., Prusiner S. B. Mutation and polymorphism of the prion protein gene in Libyan Jews with Creutzfeldt-Jakob disease (CJD). Am J Hum Genet. 1993 Oct;53(4):828–835. [PMC free article] [PubMed] [Google Scholar]
- Galvez S., Masters C., Gajdusek C. Descriptive epidemiology of Creutzfeldt-Jakob disease in Chile. Arch Neurol. 1980 Jan;37(1):11–14. doi: 10.1001/archneur.1980.00500500041004. [DOI] [PubMed] [Google Scholar]
- Gibbs C. J., Jr, Gajdusek D. C., Asher D. M., Alpers M. P., Beck E., Daniel P. M., Matthews W. B. Creutzfeldt-Jakob disease (spongiform encephalopathy): transmission to the chimpanzee. Science. 1968 Jul 26;161(3839):388–389. doi: 10.1126/science.161.3839.388. [DOI] [PubMed] [Google Scholar]
- Goldfarb L. G., Brown P., Goldgaber D., Garruto R. M., Yanagihara R., Asher D. M., Gajdusek D. C. Identical mutation in unrelated patients with Creutzfeldt-Jakob disease. Lancet. 1990 Jul 21;336(8708):174–175. doi: 10.1016/0140-6736(90)91693-5. [DOI] [PubMed] [Google Scholar]
- Goldfarb L. G., Brown P., Mitrovà E., Cervenáková L., Goldin L., Korczyn A. D., Chapman J., Gálvez S., Cartier L., Rubenstein R. Creutzfeldt-Jacob disease associated with the PRNP codon 200Lys mutation: an analysis of 45 families. Eur J Epidemiol. 1991 Sep;7(5):477–486. doi: 10.1007/BF00143125. [DOI] [PubMed] [Google Scholar]
- Goldfarb L. G., Brown P. The transmissible spongiform encephalopathies. Annu Rev Med. 1995;46:57–65. doi: 10.1146/annurev.med.46.1.57. [DOI] [PubMed] [Google Scholar]
- Goldfarb L. G., Korczyn A. D., Brown P., Chapman J., Gajdusek D. C. Mutation in codon 200 of scrapie amyloid precursor gene linked to Creutzfeldt-Jakob disease in Sephardic Jews of Libyan and non-Libyan origin. Lancet. 1990 Sep 8;336(8715):637–638. doi: 10.1016/0140-6736(90)93443-s. [DOI] [PubMed] [Google Scholar]
- Goldfarb L. G., Mitrová E., Brown P., Toh B. K., Gajdusek D. C. Mutation in codon 200 of scrapie amyloid protein gene in two clusters of Creutzfeldt-Jakob disease in Slovakia. Lancet. 1990 Aug 25;336(8713):514–515. doi: 10.1016/0140-6736(90)92073-q. [DOI] [PubMed] [Google Scholar]
- Goldgaber D., Goldfarb L. G., Brown P., Asher D. M., Brown W. T., Lin S., Teener J. W., Feinstone S. M., Rubenstein R., Kascsak R. J. Mutations in familial Creutzfeldt-Jakob disease and Gerstmann-Sträussler-Scheinker's syndrome. Exp Neurol. 1989 Nov;106(2):204–206. doi: 10.1016/0014-4886(89)90095-2. [DOI] [PubMed] [Google Scholar]
- Hainfellner J. A., Jellinger K., Diringer H., Guentchev M., Kleinert R., Pilz P., Maier H., Budka H. Die Creutzfeldt-Jakob-Krankheit in Osterreich. Wien Klin Wochenschr. 1996 Dec 13;108(23):759–763. [PubMed] [Google Scholar]
- Hsiao K., Meiner Z., Kahana E., Cass C., Kahana I., Avrahami D., Scarlato G., Abramsky O., Prusiner S. B., Gabizon R. Mutation of the prion protein in Libyan Jews with Creutzfeldt-Jakob disease. N Engl J Med. 1991 Apr 18;324(16):1091–1097. doi: 10.1056/NEJM199104183241604. [DOI] [PubMed] [Google Scholar]
- Iughetti P., Zatz M., Bueno M. R., Marie S. K. Different origins of mutations at the Machado-Joseph locus (MJD1) J Med Genet. 1996 May;33(5):439–439. doi: 10.1136/jmg.33.5.439. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Korczyn A. D. Neurologic genetic diseases of Jewish people. Biomed Pharmacother. 1994;48(8-9):391–397. doi: 10.1016/0753-3322(94)90057-4. [DOI] [PubMed] [Google Scholar]
- Long J. C., Williams R. C., Urbanek M. An E-M algorithm and testing strategy for multiple-locus haplotypes. Am J Hum Genet. 1995 Mar;56(3):799–810. [PMC free article] [PubMed] [Google Scholar]
- Masters C. L., Harris J. O., Gajdusek D. C., Gibbs C. J., Jr, Bernoulli C., Asher D. M. Creutzfeldt-Jakob disease: patterns of worldwide occurrence and the significance of familial and sporadic clustering. Ann Neurol. 1979 Feb;5(2):177–188. doi: 10.1002/ana.410050212. [DOI] [PubMed] [Google Scholar]
- Meiner Z., Gabizon R., Prusiner S. B. Familial Creutzfeldt-Jakob disease. Codon 200 prion disease in Libyan Jews. Medicine (Baltimore) 1997 Jul;76(4):227–237. doi: 10.1097/00005792-199707000-00001. [DOI] [PubMed] [Google Scholar]
- Mitrová E., Huncaga S., Hocman G., Nyitrayová O., Tatara M. "Clusters" of CJD in Slovakia: the first laboratory evidence of scrapie. Eur J Epidemiol. 1991 Sep;7(5):520–523. doi: 10.1007/BF00143133. [DOI] [PubMed] [Google Scholar]
- Mitrová E. Some new aspects of CJD epidemiology in Slovakia. Eur J Epidemiol. 1991 Sep;7(5):439–449. doi: 10.1007/BF00143119. [DOI] [PubMed] [Google Scholar]
- Miyakawa T., Inoue K., Iseki E., Kawanishi C., Sugiyama N., Onishi H., Yamada Y., Suzuki K., Iwabuchi K., Kosaka K. Japanese Creutzfeldt-Jakob disease patients exhibiting high incidence of the E200K PRNP mutation and located in the basin of a river. Neurol Res. 1998 Dec;20(8):684–688. doi: 10.1080/01616412.1998.11740584. [DOI] [PubMed] [Google Scholar]
- Salvatore M., Pocchiari M., Cardone F., Petraroli R., D'Alessandro M., Galveź S., Brown P., Macćhi G., Fieschi C., Colosimo C. Codon 200 mutation in a new family of Chilean origin with Creutzfeldt-Jakob disease. J Neurol Neurosurg Psychiatry. 1996 Jul;61(1):111–112. doi: 10.1136/jnnp.61.1.111. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sparkes R. S., Simon M., Cohn V. H., Fournier R. E., Lem J., Klisak I., Heinzmann C., Blatt C., Lucero M., Mohandas T. Assignment of the human and mouse prion protein genes to homologous chromosomes. Proc Natl Acad Sci U S A. 1986 Oct;83(19):7358–7362. doi: 10.1073/pnas.83.19.7358. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Stevanin G., Cancel G., Didierjean O., Dürr A., Abbas N., Cassa E., Feingold J., Agid Y., Brice A. Linkage disequilibrium at the Machado-Joseph disease/spinal cerebellar ataxia 3 locus: evidence for a common founder effect in French and Portuguese-Brazilian families as well as a second ancestral Portuguese-Azorean mutation. Am J Hum Genet. 1995 Nov;57(5):1247–1250. [PMC free article] [PubMed] [Google Scholar]
- Takiyama Y., Igarashi S., Rogaeva E. A., Endo K., Rogaev E. I., Tanaka H., Sherrington R., Sanpei K., Liang Y., Saito M. Evidence for inter-generational instability in the CAG repeat in the MJD1 gene and for conserved haplotypes at flanking markers amongst Japanese and Caucasian subjects with Machado-Joseph disease. Hum Mol Genet. 1995 Jul;4(7):1137–1146. doi: 10.1093/hmg/4.7.1137. [DOI] [PubMed] [Google Scholar]
- Windl O., Dempster M., Estibeiro J. P., Lathe R., de Silva R., Esmonde T., Will R., Springbett A., Campbell T. A., Sidle K. C. Genetic basis of Creutzfeldt-Jakob disease in the United Kingdom: a systematic analysis of predisposing mutations and allelic variation in the PRNP gene. Hum Genet. 1996 Sep;98(3):259–264. doi: 10.1007/s004390050204. [DOI] [PubMed] [Google Scholar]