Trinucleotide repeats and long homopeptides in genes and proteins associated with nervous system disease and development.

Karlin, Samuel; Burge, C

doi:10.1073/pnas.93.4.1560

Cited by 171 publications

(130 citation statements)

References 20 publications

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“…7). Previous research on smaller eukaryote data sets also note that repeat tracts are overrepresented in transcription factors and DNA-binding proteins (Karlin and Burge 1996;Mar Alba et al 1999;Alba et al 2002;Alba and Guigo 2004). The results of this study are consistent with these findings and identify other functional classes rich in RCPs.…”

Section: Genome Research 547supporting

confidence: 82%

“…The vast majority (87%) of all RCPs are from eukaryotes; prokaryote RCPs are rare (4%) ( Table 1). This is in agreement with previous studies (Karlin and Burge 1996;Marcotte et al 1999;Huntley and Golding 2000). Within GENPEPT, poly-Q repeats are the most common (16%), whereas poly-W repeats are extremely rare (only three poly-W RCPs could be identified) (Fig.…”

Section: A Web-accessible Database Of Rcpssupporting

confidence: 82%

“…Furthermore, the function (if any) of a typical poly-Q tract remains to be determined. In contrast, studies focusing on the function of poly-Q RCPs have revealed interesting functional patterns; an investigation of Drosophila melanogaster poly-Q RCPs revealed that many of these proteins are transcription factors involved in development (Karlin and Burge 1996;Alba and Guigo 2004).…”

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confidence: 99%

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Functional insights from the distribution and role of homopeptide repeat-containing proteins

Faux¹,

Bottomley²,

Lesk³

et al. 2005

Genome Res.

191

221

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Expansion of “low complex” repeats of amino acids such as glutamine (Poly-Q) is associated with protein misfolding and the development of degenerative diseases such as Huntington's disease. The mechanism by which such regions promote misfolding remains controversial, the function of many repeat-containing proteins (RCPs) remains obscure, and the role (if any) of repeat regions remains to be determined. Here, a Web-accessible database of RCPs is presented. The distribution and evolution of RCPs that contain homopeptide repeats tracts are considered, and the existence of functional patterns investigated. Generally, it is found that while polyamino acid repeats are extremely rare in prokaryotes, several eukaryote putative homologs of prokaryote RCP—involved in important housekeeping processes—retain the repetitive region, suggesting an ancient origin for certain repeats. Within eukarya, the most common uninterrupted amino acid repeats are glutamine, asparagines, and alanine. Interestingly, while poly-Q repeats are found in vertebrates and nonvertebrates, poly-N repeats are only common in more primitive nonvertebrate organisms, such as insects and nematodes. We have assigned function to eukaryote RCPs using Online Mendelian Inheritance in Man (OMIM), the Human Reference Protein Database (HRPD), FlyBase, and Wormpep. Prokaryote RCPs were annotated using BLASTp searches and Gene Ontology. These data reveal that the majority of RCPs are involved in processes that require the assembly of large, multiprotein complexes, such as transcription and signaling

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Section: Genome Research 547supporting

confidence: 82%

Section: A Web-accessible Database Of Rcpssupporting

confidence: 82%

mentioning

confidence: 99%

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Functional insights from the distribution and role of homopeptide repeat-containing proteins

Faux¹,

Bottomley²,

Lesk³

et al. 2005

Genome Res.

191

221

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“…The human genome contains arrays of tandem nucleotide repeats, the length of which may be polymorphic across the population (Craig-Holmes & Shaw 1971, Weber 1990, Karlin & Burge 1996. Trinucleotide repeat sequences are characterized by their ability to undergo dynamic mutation or nucleotide alteration over a compressed time span of only a few generations.…”

Section: Overview Of the Trinucleotide Repeats And Neurodegenerative mentioning

confidence: 99%

Trinucleotide repeats in the human androgen receptor: a molecular basis for disease

Choong¹,

Wilson²

1998

Journal of Molecular Endocrinology

123

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“…Notably the fly sequence has an opa triplet repeat at the amino terminus that is not present in any of the vertebrate sequences defined so far. Triplet repeats tend to be associated with genes important to nervous system function and development; expansion of such triplet repeats is associated with a number of human neurodegen- erative diseases (Ashley and Warren 1995;Karlin and Burge 1996). As mutation of the fly gene leads to cell death, at least in the eye (Bonini et al 1993), it will be of interest to determine whether there may be an additional vertebrate eya homolog that contains this repeat or whether there are alternative splice products of the currently defined genes that contain a triplet repeat.…”

Section: Eya Gene Familymentioning

confidence: 99%

Cloning and characterization of two vertebrate homologs of the Drosophila eyes absent gene.

et al. 1997

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The Drosophila eyes absent (eya) gene plays an essential role in the events that lead to proper development of the fly eye and embryo. Here we report the analysis of two human and two mouse homologs of the fly eya gene.Sequence comparison reveals a large domain of -270 amino acids in the carboxyl terminus of the predicted mammalian proteins that shows 53% identity between the fly sequence and all of the vertebrate homologs. This Eya-homology domain is of novel sequence, with no previously identified motifs. RNA hybridization studies indicate that the mouse genes are expressed during embryogenesis and in select tissues of the adult. Both mouse Eya genes are expressed in the eye, suggesting that these genes may function in eye development in vertebrates as eya does in the fly. The mouse Eya2 gene maps to chromosome 2 in the region syntenic with human chromosome 20q13, and the mouse Eya$ gene maps to chromosome 4 in the region syntenic with human chromosome lp36. Our findings support the notion that several families of genes (Pax-6/eyeless, $ix-3/sine oculis, and Eya) play related and critical roles in the eye for both flies and vertebrates.

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Trinucleotide repeats and long homopeptides in genes and proteins associated with nervous system disease and development.

Abstract: Several human neurological disorders are associated with proteins containing abnormally long runs of glutamine residues. Strikingly, most of these proteins contain two or more additional long runs of amino acids other than glutamine. We screened the current human, mouse,

Cited by 171 publications

References 20 publications

Functional insights from the distribution and role of homopeptide repeat-containing proteins

Functional insights from the distribution and role of homopeptide repeat-containing proteins

Trinucleotide repeats in the human androgen receptor: a molecular basis for disease

Cloning and characterization of two vertebrate homologs of the Drosophila eyes absent gene.

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