Isolation of a GCC repeat showing expansion in FRAXF, a fragile site distal to FRAXA and FRAXE

Parrish, Julia E.; Oostra, Ben A.; Verkerk, Annemieke J.M.H.; Richards, C. Sue; Reynolds, Joanna; Spikes, Aimee S.; Shaffer, Lisa G.; Nelson, David L.

doi:10.1038/ng1194-229

Cited by 158 publications

(81 citation statements)

References 11 publications

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“…The mental retardation is associated with dysmorphic features such as enlarged ears, head, and testicles. The primary genetic defect in fragile X syndrome is an expanded CGG repeat The repeat is found in the 5'untranslated region of the gene called FMR-I (25). The gene product is a member of a family of RNA-binding proteins and is widely expressed in fetal and adult tissues, most abundantly in the neurons.…”

Section: Fragile X Syndromementioning

confidence: 99%

Trinucleotide repeats and neuropsychiatric disorders

Shetty

Christopher

2000

Indian J Clin Biochem

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Expansions of trinucleotide repeats at the level of genomic DNA are increasingly recognized as a cause of a number of neuropsychiatric disorders, Triplet repeat disorders are commonly classified into two groups, those with moderate CAG expansions that result in a polyglutamine stretch in the gene products and those with very long expansions, usually non-CAG, that are not translated. The triplet repeat intergeneration and intra-generational instability, and genetic anticipation characterize disorders. Most of the diseases caused by expanded CAG repeat share common features, which include neurodegeneration, a dominant pattern of inheritance and widespread expression of the gene products with neuronal loss restricted to distinct subset of neurons. Neurodegenerative changes associated of CAG expansion disorders is explained in terms of intra and extra cellular aggregation of mutant gene products, the insoluble nature of the protein(s) being attributed to the presence of polyglutamine stretches, hence their neurotoxic effects. Methods based on poymerase chain reaction have become handy in the diagnosis of these genetic disorders. Progress in transgenic animal models for these disorders will be critical for understanding the progress of these disorders and for testing new therapeutic strategies.

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Section: Fragile X Syndromementioning

confidence: 99%

Trinucleotide repeats and neuropsychiatric disorders

Shetty

Christopher

2000

Indian J Clin Biochem

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“…The fragile sites can be classi®ed as common or rare, based upon the frequency of their occurrence in the human population (Sutherland and Hecht, 1985). Expression of the known cloned rare fragile sites is associated with the expansion of trinucleotide or minisatellite sequences (Fu et al, 1991;Knight et al, 1993;Parrish et al, 1994;Jones et al, 1994;Yu et al, 1997). Common fragile sites appear to be present in all individuals and most are induced by the DNA polymerase a inhibitor aphidicolin (Glover et al, 1984).…”

Section: Introductionmentioning

confidence: 99%

Frequent homozygous deletions in the FRA3B region in tumor cell lines still leave the FHIT exons intact

et al. 1998

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FRA3B at human chromosomal band 3p14.2 is the most active common fragile site in the human genome. The molecular mechanism of fragility at this region remains unknown but does not involve expansion of a trinucleotide or minisatellite repeat as has been observed for several of the cloned rare fragile sites. Deletions and rearrangements at FRA3B have been observed in a number of distinct tumors. The recently identi®ed putative tumor suppressor gene FHIT spans FRA3B, and various groups have reported identifying deletions in this gene in dierent tumors. Using a high density of PCR ampli®able markers within FRA3B searching for deletions in the FRA3B region, we have analysed 21 tumor cell lines derived from renal cell, pancreatic, and ovarian carcinomas. We found a commonly deleted region in the renal cell and ovarian carcinoma cell lines located in the middle of an HPV16 viral integration site. Despite the presence of deletions in the FRA3B region in most of the cell lines, we did not detect alterations in FHIT exons in any of the cell lines examined. Thus, deletions of 3p14.2 in these carcinoma cell lines may simply re¯ect instability of the FRA3B region during tumor progression.

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“…These are termed FRA X E 11 and FRA X F, 12 both of which can be detected by routine cytogenetic methods, although differentiating between all three fragile sites is extremely difficult. FRA X E positive individuals were shown to be associated with a milder form of mental retardation compared to fragile X syndrome.…”

mentioning

confidence: 99%

“…Both FRA X E and FRA X F were shown by molecular techniques to be due to expansion of GCC trinucleotide repeats in the vicinity of CpG islands in the Xq28 region. [11][12] The laboratory diagnosis of fragile X syndrome can be achieved easily and reliably by molecular techniques such as Southern blotting or polymerase chain reaction (PCR) methodology. In addition, fragile X chromosome screening by special cytogenetic techniques can also diagnose the syndrome in a majority of affected males (99%) and in 90%-95% of affected females.…”

mentioning

confidence: 99%