Selective Forces Related to Spinocerebellar Ataxia Type 2.
Anticipation
CAG repeats
Reproductive success
SCA2
Segregation distortion
Spinocerebellar ataxia type 2
Journal
Cerebellum (London, England)
ISSN: 1473-4230
Titre abrégé: Cerebellum
Pays: United States
ID NLM: 101089443
Informations de publication
Date de publication:
04 2019
04 2019
Historique:
pubmed:
17
9
2018
medline:
31
7
2019
entrez:
17
9
2018
Statut:
ppublish
Résumé
Spinocerebellar ataxia type 2 (SCA2) is caused by an unstable expanded CAG repeat tract (CAGexp) at ATXN2. Although prone to selective forces such as anticipation, SCA2 frequency seems to be stable in populations. Our aim was to estimate reproductive success, segregation patterns, and role of anticipation in SCA2. Adult subjects from families with molecular diagnosis provided data about all his/her relatives. Affected and unaffected sibs older than 65.7 years of age were used to estimate reproductive success and segregation patterns. Twenty-one SCA2 families were studied, including 1017 individuals (164 affected) who were born from 1840 to 2012. The median number of children of the non-carriers and carriers, among 99 subjects included in the reproductive success analysis, were 2 and 3 (p < 0.025), respectively. Therefore, the reproductive success of carriers was 1.5. There were 137 non-carriers (59.6%) and 93 carriers (40.4%) (p = 0.04), among subjects included in the segregation analysis. Age at onset across generations pointed to anticipation as a frequent phenomenon. We raised evidence in favor of increased reproductive success related to the carrier state at ATXN2, and segregation distortion favoring normal alleles. Since majority of normal alleles analyzed carried 22 repeats, we propose that this distortion segregation can be related to the high frequency of this allele in human chromosomes.
Identifiants
pubmed: 30219976
doi: 10.1007/s12311-018-0977-7
pii: 10.1007/s12311-018-0977-7
doi:
Substances chimiques
ATXN2 protein, human
0
Ataxin-2
0
Types de publication
Journal Article
Langues
eng
Pagination
188-194Subventions
Organisme : Fundo de Incentivo à Pesquisa do Hospital de Clínicas de Porto Alegre (FIPE-HCPA)
ID : GPPG HCPA 16-320
Pays : International
Commentaires et corrections
Type : ErratumIn
Pereira MLS [corrected to Saraiva-Pereira ML]
Références
Pulst SM. Spinocerebellar ataxia type 2. GeneReviews® [Internet].2015. https://www.ncbi.nlm.nih.gov/books/NBK1275/
Laffita-Mesa JM, Velázquez-Pérez LC, Santos Falcón N, et al. Unexpanded and intermediate CAG polymorphisms at the SCA2 locus (ATXN2) in the Cuban population: evidence about the origin of expanded SCA2 alleles. European Journal of Human Genetics. 2012;20(1):41–9. https://doi.org/10.1038/ejhg.2011.15 .
doi: 10.1038/ejhg.2011.154
pubmed: 21934711
Montcel S.T, Durr A, Bauer P, et al. Modulation of the age at onset in spinocerebellar ataxia by CAG tracts in various genes. Brain 2014. Pages 2444–2455.
Geschwind DH, Perlman S, Figueroa CP, Treiman LJ, Pulst SM. The prevalence and wide clinical spectrum of the spinocerebellar ataxia type 2 trinucleotide repeat in patients with autosomal dominant cerebellar ataxia. Am J Hum Genet. 1997;60(4):842–50.
pubmed: 9106530
pmcid: 1712476
Matilla-Dueñas A, Sánchez I, Corral-Juan M, Dávalos A, Alvarez R, Latorre P. Cellular and molecular pathways triggering neurodegeneration in the spinocerebellar ataxias. Cerebellum. 2010 Jun;9(2):148–66.
doi: 10.1007/s12311-009-0144-2
pubmed: 19890685
Magaña JJ, Velázquez-Pérez L, Cisneros B. Spinocerebellar ataxia type 2: clinical presentation, molecular mechanisms, and therapeutic perspectives. Mol Neurobiol. 2013;47:90–104.
doi: 10.1007/s12035-012-8348-8
pubmed: 22996397
Auburger GW. Spinocerebellar ataxia type 2. Handb Clin Neurol. 2012;103:423–36.
doi: 10.1016/B978-0-444-51892-7.00026-7
pubmed: 21827904
Costanzi-Porrini S, Tessarolo D, Abbruzzese C, Liguori M, Ashizawa T, Giacanelli M. An interrupted 34-CAG repeat SCA-2 allele in patients with sporadic spinocerebellar ataxia. Neurology. 2000 Jan 25;54(2):491–3.
doi: 10.1212/WNL.54.2.491
pubmed: 10668721
Babovic-Vuksanovic D, Snow K, Patterson MC, Michels VV. Spinocerebellar ataxia type 2 (SCA 2) in an infant with extreme CAG repeat expansion. Am J Med Genet. 1998;79:383–7.
doi: 10.1002/(SICI)1096-8628(19981012)79:5<383::AID-AJMG10>3.0.CO;2-N
pubmed: 9779806
Abdel-Aleem A, Zaki MS. Spinocerebellar ataxia type 2 (SCA2) in an Egyptian family presenting with polyphagia and marked CAG expansion in infancy. J Neurol. 2008;255:413–9.
doi: 10.1007/s00415-008-0690-4
pubmed: 18297329
Di Fabio R, Santorelli F, Bertini E, et al. Infantile childhood onset of spinocerebellar ataxia type 2. Cerebellum. 2012;11:526–30.
doi: 10.1007/s12311-011-0315-9
pubmed: 21975856
Figueroa KP, Coon H, Santos N, et al. Genetic analysis of age at onset variation in spinocerebellar ataxia type 2. Neurology: Genetics. 2017;3(3):e155.
Almaguer-Mederos LE, Mesa JML, González-Zaldívar Y, et al. Factors associated with ATXN2 CAG/CAA repeat intergenerational instability in spinocerebellar ataxia type 2. Clin Genet. 2018:14.
Frontali M, Sabbadini G, Novelletto A, et al. Genetic fitness in Huntington’s Disease and Spinocerebellar Ataxia 1: a population genetics model for CAG repeat expansions. 1996.
Prestes PR, Saraiva-Pereira ML, Silveira I, Sequeiros J, Jardim LB. Machado Joseph disease enhances genetic fitness: a comparison between affected and unaffected women and between MJD and the general population. Ann Hum Genet. 2008;72:57–64.
pubmed: 17683516
Souza GN, Kersting N, Krum-Santos AC, Santos ASP, Furtado GV, Pacheco D, et al. Spinocerebellar ataxia type 3/Machado-Joseph disease: segregation patterns and factors influencing instability of expanded CAG transmissions. Clin Genet. 2016 Aug;90(2):134–40.
doi: 10.1111/cge.12719
pubmed: 26693702
Platonov FA, Tyryshkin K, Tikhonov DG, Neustroyeva TS, Sivtseva TM, Yakovleva NV, et al. Genetic fitness and selection intensity in a population affected with high-incidence spinocerebellar ataxia type 1. Neurogenetics. 2016;17(3):179–85.
doi: 10.1007/s10048-016-0481-5
pubmed: 27106293
pmcid: 5262524
Pereira FS, Monte TL, Locks-Coelho LD. Genes and mitochondrial polymorphism A10398G did not modify age at onset in spinocerebellar ataxia type 2 patients from South America. Cerebellum. 2015 Dec;14(6):728–30.
doi: 10.1007/s12311-015-0666-8
pubmed: 25869926
Socal MP, Emmel VE, Rieder CR. Intrafamilial variability of Parkinson phenotype in SCAs: novel cases due to SCA2 and SCA3 expansions. Parkinsonism Relat Disord. 2009;15:374–8.
doi: 10.1016/j.parkreldis.2008.09.005
pubmed: 18990604
de Castilhos RM, Furtado GV, Gheno TC, et al. Spinocerebellar ataxias in Brazil--frequencies and modulating effects of related. Cerebellum. 2014;13:17–28.
Thul PJ, Åkesson L, Wiking M, Mahdessian D, Geladaki A, Ait Blal H, et al. A subcellular map of the human proteome. Science. 2017;356:eaal3321.
doi: 10.1126/science.aal3321
pubmed: 28495876
Human Protein Atlas available from www.proteinatlas.org.
Lorenzetti D, Bohlega S, Zoghbi HY. The expansion of the CAG repeat in ataxin-2 is a frequent cause of autosomal dominant spinocerebellar ataxia. Neurology. Oct 1997;49(4):1009–13.
doi: 10.1212/WNL.49.4.1009
pubmed: 9339681
Mao R, Aylsworth AS, Potter N, Wilson WG, Breningstall G, Wick MJ, et al. Childhood-onset ataxia: testing for large CAG-repeats in SCA2 and SCA7. Am J Med Genet. 2002;110:338–45.
doi: 10.1002/ajmg.10467
pubmed: 12116207
Pulst S-M, Nechiporuk A, Nechiporuk T, Gispert S, Chen X-N, Lopes-Cendes I, et al. Moderate expansion of a normally biallelic trinucleotide repeat in spinocerebellar ataxia type 2. Nat Genet. 1996;14:269–76. https://doi.org/10.1038/ng1196-269 .
doi: 10.1038/ng1196-269
pubmed: 8896555
McMurray CT. Mechanisms of trinucleotide repeat instability during human development. Nat Rev Genet. 2010;11(11):786–99. https://doi.org/10.1038/nrg2828 .
doi: 10.1038/nrg2828
pubmed: 20953213
pmcid: 3175376