Childhood‐onset ataxia: Testing for large CAG‐repeats in SCA2 and SCA7

Mao, Rong; Aylsworth, Arthur S.; Potter, Nicholas; Wilson, William G.; Breningstall, Galen N.; Wick, Myra J.; Babovic‐Vuksanovic, Dusica; Nance, Martha; Patterson, Marc C.; Gómez, Christopher M.; Snow, Karen

doi:10.1002/ajmg.10467

Cited by 72 publications

(79 citation statements)

References 21 publications

(46 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…While a recent study by Woodhead et al (2005) revealed that estimates of population differentiation based on EST-SSRs are comparable to those based on both anonymous SSRs and AFLPs in ferns, and large-scale comparative analyses suggest that only a very small percentage of all genes are experiencing positive selection (Tiffin and Hahn, 2002;Clark et al, 2003), some small fraction of all EST-SSRs will inevitably be subject to selection. Indeed, there are examples from the literature wherein certain genic SSRs are known to be associated with various diseases in animals (Zoghbi and Orr, 2000;Mao et al, 2002;Yamada et al, 2002) or pathogenicity/virulence in microbes (Peak et al, 1996;Grimwood et al, 2001). While more studies are needed before we will have a better understanding of the possible effects of genic SSRs in plants (Li et al, 2004), it seems safe to assume that at least a small percentage of loci will be evolving in a non-neutral manner.…”

Section: Jr Ellis and Jm Burkementioning

confidence: 99%

EST-SSRs as a resource for population genetic analyses

2007

View full text Add to dashboard Cite

Simple-sequence repeats (SSRs) have increasingly become the marker of choice for population genetic analyses. Unfortunately, the development of traditional 'anonymous' SSRs from genomic DNA is costly and time-consuming. These problems are further compounded by a paucity of resources in taxa that lack clear economic importance. However, the advent of the genomics age has resulted in the production of vast amounts of publicly available DNA sequence data, including large collections of expressed sequence tags (ESTs) from a variety of different taxa. Recent research has revealed that ESTs are a potentially rich source of SSRs that reveal polymorphisms not only within the source taxon, but in related taxa, as well. In this paper, we review what is known about the transferability of EST-SSRs from one taxon to another with particular reference to the potential of these markers to facilitate population genetic studies. As an example of the utility of these resources, we then cross-reference existing EST databases against lists of rare, endangered and invasive plant species and conclude that half of all suitable EST databases could be exploited for the population genetic analysis of species of conservation concern. We then discuss the advantages and disadvantages of EST-SSRs in the context of population genetic applications.

show abstract

Section: Jr Ellis and Jm Burkementioning

confidence: 99%

EST-SSRs as a resource for population genetic analyses

2007

View full text Add to dashboard Cite

show abstract

“…6 Only few patients having 32 and 33 CAG repeats have been reported so far, with very late onset -between 50 and 60 years of age. 4,7,8 Extremely large expansions of 109, 200 and 500 CAG in infants have also been observed, [9][10][11] but are rarer.…”

Section: Spinocerebellar Ataxia Type 2 (Sca2) Is a Neurodegenerative mentioning

confidence: 99%

Unexpanded and intermediate CAG polymorphisms at the SCA2 locus (ATXN2) in the Cuban population: evidence about the origin of expanded SCA2 alleles

Laffita-Mesa¹,

Velázquez‐Pérez²,

Falcón³

et al. 2011

Eur J Hum Genet

View full text Add to dashboard Cite

The role of short, large or intermediate normal alleles (ANs) of the ataxin-2 gene in generating expanded alleles (EAs) causing spinocerebellar ataxia type 2 (SCA2) is poorly understood. It has been postulated that SCA2 prevalence is related to the frequency of large ANs. SCA2 shows the highest worldwide prevalence in Cuban population, which is therefore a unique source for studying the relationship between the frequency of large and intermediate alleles and the frequency of SCA2 mutation. Through genetic polymorphism analyses in a comprehensive sample (B3000 chromosomes), we show that the frequency of large ANs in the ataxin-2 gene is the highest worldwide, although short ANs are also frequent. This highly polymorphic population displayed also high variability in the CAG sequence, featured by loss of the anchor CAA interruption(s). In addition, large ANs showed germinal and somatic instability. Our study also includes related genotypic, genealogical and haplotypic data and provides substantial evidence with regard to the role of large and intermediate alleles in the generation of pathological EAs.

show abstract

“…Death occurs early. Brain MRI showed extreme cerebellar and brainstem atrophy, but also different degrees of supratentorial atrophy and ventricular enlargement, and white matter signal abnormalities likely attributable to dysmyelination and/or delayed myelination 70, 71, 72, 73…”

Section: Infantile Formsmentioning

confidence: 99%

The Multiple Faces of Spinocerebellar Ataxia type 2

Antenora

Rinaldi

Roca

et al. 2017

Ann Clin Transl Neurol

View full text Add to dashboard Cite

Spinocerebellar ataxia type 2 (SCA2) is among the most common forms of autosomal dominant ataxias, accounting for 15% of the total families. Occurrence is higher in specific populations such as the Cuban and Southern Italian. The disease is caused by a CAG expansion in ATXN2 gene, leading to abnormal accumulation of the mutant protein, ataxin‐2, in intracellular inclusions. The clinical picture is mainly dominated by cerebellar ataxia, although a number of other neurological signs have been described, ranging from parkinsonism to motor neuron involvement, making the diagnosis frequently challenging for neurologists, particularly when information about the family history is not available. Although the functions of ataxin‐2 have not been completely elucidated, the protein is involved in mRNA processing and control of translation. Recently, it has also been shown that the size of the CAG repeat in normal alleles represents a risk factor for ALS, suggesting that ataxin‐2 plays a fundamental role in maintenance of neuronal homeostasis.

show abstract

Childhood‐onset ataxia: Testing for large CAG‐repeats in SCA2 and SCA7

Cited by 72 publications

References 21 publications

EST-SSRs as a resource for population genetic analyses

EST-SSRs as a resource for population genetic analyses

Unexpanded and intermediate CAG polymorphisms at the SCA2 locus (ATXN2) in the Cuban population: evidence about the origin of expanded SCA2 alleles

The Multiple Faces of Spinocerebellar Ataxia type 2

Contact Info

Product

Resources

About