ATXN2
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Ataxin-2 is a protein that in humans is encoded by the ATXN2 gene.[4][5]
Mutations in ATXN2 cause spinocerebellar ataxia type 2 (SCA2). The autosomal dominant cerebellar ataxias (ADCA) are a heterogeneous group of neurodegenerative disorders characterized by progressive degeneration of the cerebellum, brain stem and spinal cord. Clinically, ADCA has been divided into three groups: ADCA types I-III. ADCAI is genetically heterogeneous, with five genetic loci, designated spinocerebellar ataxia (SCA) 1, 2, 3, 4 and 6, being assigned to five different chromosomes. ADCAII, which always presents with retinal degeneration (SCA7), and ADCAIII often referred to as the `pure' cerebellar syndrome (SCA5), are most likely homogeneous disorders. Several SCA genes have been cloned and shown to contain CAG repeats in their coding regions. SCA2 is caused by the expansion of a CAG repeat in the coding region of the ATXN2 gene producing an elongated polyglutamine tract in the corresponding protein. The expanded repeats are variable in size and unstable, usually increasing in size when transmitted to successive generations. The function of the ataxins is not known. This locus has been mapped to chromosome 12, and it has been determined that the disease allele usually contains 34-52 CAG repeats, but can contain as few as 32 or more than 100. Normal alleles usually have 22 or 23 repeats, but can contain up to 31 repeats. A potential transcript variant, missing an internal coding exon, has been described; however, its full-length nature is not certain.[6]
In 2010, work from Aaron Gitler and Nancy Bonini at the University of Pennsylvania discovered that intermediate-size CAG repeat expansions are significantly associated with risk for developing amyotrophic lateral sclerosis (Lou Gehrig's disease).[7]
References
- ↑ "Diseases that are genetically associated with ATXN2 view/edit references on wikidata".
- ↑ "Human PubMed Reference:".
- ↑ "Mouse PubMed Reference:".
- ↑ Gispert S, Twells R, Orozco G, Brice A, Weber J, Heredero L, Scheufler K, Riley B, Allotey R, Nothers C, et al. (Sep 1993). "Chromosomal assignment of the second locus for autosomal dominant cerebellar ataxia (SCA2) to chromosome 12q23-24.1". Nat Genet. 4 (3): 295–9. doi:10.1038/ng0793-295. PMID 8358438.
- ↑ Margolis RL, Abraham MR, Gatchell SB, Li SH, Kidwai AS, Breschel TS, Stine OC, Callahan C, McInnis MG, Ross CA (Jul 1997). "cDNAs with long CAG trinucleotide repeats from human brain". Hum Genet. 100 (1): 114–22. doi:10.1007/s004390050476. PMID 9225980.
- ↑ "Entrez Gene: ATXN2 ataxin 2".
- ↑ Elden AC, Kim HJ, Hart MP, Chen-Plotkin AS, Johnson BS, Fang X, Armakola M, Geser F, Greene R, Lu MM, et al. (Aug 2010). "Ataxin-2 intermediate-length polyglutamine expansions are associated with increased risk for ALS". Nature. 466 (7310): 1069–1075. doi:10.1038/nature09320. PMC 2965417
. PMID 20740007.
Further reading
- Stevanin G, Dürr A, Brice A (2000). "Clinical and molecular advances in autosomal dominant cerebellar ataxias: from genotype to phenotype and physiopathology.". Eur. J. Hum. Genet. 8 (1): 4–18. doi:10.1038/sj.ejhg.5200403. PMID 10713882.
- Pulst SM, Nechiporuk A, Nechiporuk T, et al. (1996). "Moderate expansion of a normally biallelic trinucleotide repeat in spinocerebellar ataxia type 2.". Nat. Genet. 14 (3): 269–76. doi:10.1038/ng1196-269. PMID 8896555.
- Sanpei K, Takano H, Igarashi S, et al. (1996). "Identification of the spinocerebellar ataxia type 2 gene using a direct identification of repeat expansion and cloning technique, DIRECT.". Nat. Genet. 14 (3): 277–84. doi:10.1038/ng1196-277. PMID 8896556.
- Imbert G, Saudou F, Yvert G, et al. (1996). "Cloning of the gene for spinocerebellar ataxia 2 reveals a locus with high sensitivity to expanded CAG/glutamine repeats.". Nat. Genet. 14 (3): 285–91. doi:10.1038/ng1196-285. PMID 8896557.
- Sahba S, Nechiporuk A, Figueroa KP, et al. (1998). "Genomic structure of the human gene for spinocerebellar ataxia type 2 (SCA2) on chromosome 12q24.1.". Genomics. 47 (3): 359–64. doi:10.1006/geno.1997.5131. PMID 9480749.
- Huynh DP, Del Bigio MR, Ho DH, Pulst SM (1999). "Expression of ataxin-2 in brains from normal individuals and patients with Alzheimer's disease and spinocerebellar ataxia 2.". Ann. Neurol. 45 (2): 232–41. doi:10.1002/1531-8249(199902)45:2<232::AID-ANA14>3.0.CO;2-7. PMID 9989626.
- Huynh DP, Figueroa K, Hoang N, Pulst SM (2000). "Nuclear localization or inclusion body formation of ataxin-2 are not necessary for SCA2 pathogenesis in mouse or human.". Nat. Genet. 26 (1): 44–50. doi:10.1038/79162. PMID 10973246.
- Affaitati A, de Cristofaro T, Feliciello A, Varrone S (2001). "Identification of alternative splicing of spinocerebellar ataxia type 2 gene.". Gene. 267 (1): 89–93. doi:10.1016/S0378-1119(01)00402-4. PMID 11311558.
- Kiehl TR, Shibata H, Vo T, et al. (2002). "Identification and expression of a mouse ortholog of A2BP1.". Mamm. Genome. 12 (8): 595–601. doi:10.1007/s00335-001-2056-4. PMID 11471052.
- Choudhry S, Mukerji M, Srivastava AK, et al. (2002). "CAG repeat instability at SCA2 locus: anchoring CAA interruptions and linked single nucleotide polymorphisms.". Hum. Mol. Genet. 10 (21): 2437–46. doi:10.1093/hmg/10.21.2437. PMID 11689490.
- Pang JT, Giunti P, Chamberlain S, et al. (2002). "Neuronal intranuclear inclusions in SCA2: a genetic, morphological and immunohistochemical study of two cases.". Brain. 125 (Pt 3): 656–63. doi:10.1093/brain/awf060. PMID 11872620.
- Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
- Satterfield TF, Jackson SM, Pallanck LJ (2003). "A Drosophila homolog of the polyglutamine disease gene SCA2 is a dosage-sensitive regulator of actin filament formation". Genetics. 162 (4): 1687–702. PMC 1462369. PMID 12524342.
- Wiedemeyer R, Westermann F, Wittke I, et al. (2003). "Ataxin-2 promotes apoptosis of human neuroblastoma cells". Oncogene. 22 (3): 401–11. doi:10.1038/sj.onc.1206150. PMID 12545161.
- Payami H, Nutt J, Gancher S, et al. (2003). "SCA2 may present as levodopa-responsive parkinsonism". Mov. Disord. 18 (4): 425–9. doi:10.1002/mds.10375. PMID 12671950.
- Svetel M, Djarmati A, Dragasević N, et al. (2003). "SCA2 and SCA3 mutations in young-onset dopa-responsive parkinsonism". Eur. J. Neurol. 10 (5): 597. doi:10.1046/j.1468-1331.2003.00671.x. PMID 12940846.
- Brenneis C, Bösch SM, Schocke M, et al. (2003). "Atrophy pattern in SCA2 determined by voxel-based morphometry". NeuroReport. 14 (14): 1799–802. doi:10.1097/01.wnr.0000094105.16607.18. PMID 14534423.