Variation of the CGG repeat at the fragile X site results in genetic instability: Resolution of the Sherman paradox

Fu, Ying‐Hui; Kuhl, Derek P.A.; Pizzuti, Antonio; Pieretti, Maura; Sutcliffe, James S.; Richards, Stephen M.; Verkert, Annemieke J.M.H.; Holden, Jeanette J. A.; Fenwick, Raymond G.; Warren, Stephen T.; Oostra, Ben A.; Nelson, David L.; Caskey, C. Thomas

doi:10.1016/0092-8674(91)90283-5

Cited by 1,866 publications

(1,276 citation statements)

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“…In animal species extensive variation of trinucleotide repeats in coding sequences has also been observed (Edwards et a/., 1991), and expansion of trinucleotide microsatellites within coding sequences in humans has been shown to be linked with major genetic disease, such as Kennedy's disease (La Spada eta/., 1991), fragile X syndrome (Fu et a/., 1991) and myotonic dystrophy (Brook eta/., 1992).…”

Section: Discussionmentioning

confidence: 99%

PCR‐amplified microsatellites as markers in plant genetics

1993

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SummaryIn order to assess the feasibility of using microsatellites as markers in plant genetics, a survey of published DNA sequence data for presence, abundance and ubiquity in higher plants of all types of dinucleotide and trinucleotide repeats with a minimum number of 10 and 7 units, respectively, was conducted. This search revealed that such microsatellites are frequent and widely distributed; they were uncovered in 34 species, with a frequency of one every 50 kb. AT repeats were by far the most frequently observed class of dinucleotide microsatellites, whereas ACffG repeats, which are common in animals, were observed only once. TAT repeats prevailed among trinucleotides. Polymerase chain reaction amplification of (AT), and (TAT), microsatellites in soybean (Glycine max (L.) Merr.) revealed that they are highly polymorphic, as a consequence of length variation, somatically stable and inherited in a co-dominant Mendelian manner. The abundance and amount of information derived from such markers, together with the ease by which they can be identified, make them ideal markers for plant genetic linkage and physical mapping, population studies and varietal identification.

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Section: Discussionmentioning

confidence: 99%

PCR‐amplified microsatellites as markers in plant genetics

1993

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“…19 The reaction product was analysed on an ABI310 (Applied Biosystems, Foster City, CA, USA). Data generation and evaluation have been performed in different centres following similar procedures.…”

Section: Molecular Analysismentioning

confidence: 99%

Intermediate FMR1 alleles and cognitive and/or behavioural phenotypes

et al. 2011

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During the last few years, several studies have reported an excess of intermediate FMR1 alleles in patients with cognitive and/or behavioural phenotypes. Here, we report the frequency of intermediate alleles (IAs) in three pathologies, intellectual disabilities (IDs), attention-deficit/hyperactivity disorder and autism, from different Spanish regions. We found 142 IAs among 9015 patients with ID (1.6%), 4 among the 415 ADHD patients (0.96%) and 4 among the 300 autistic patients (1.3%), similar to the frequency reported in our control population. No evidence was found of an excess of IA at the FRAXA locus in any of the study populations, although geographical variability was detected. Moreover, the analysis of 100 transmissions of IAs showed that 95% of these alleles were stable. Only 3% expanded within the same range and 2% expanded to a full mutation in two generations. No evidence of an association between IAs and behavioural or cognitive phenotypes was found, suggesting that IAs are not clearly implicated in these pathologies.

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“…(25) The length of CGG repeat in the 5 0 UTR of fragile X mental retardation gene (FMR1) is also tightly correlated with methylation of the promoter and hence transcription of the gene. (26) Apart from epigenetic regulation, the number of genetic lesions and nature of functional domain altered by mutation or polymorphism may contribute to phenotypic variability in complex diseases.…”

Section: Molecular Basis Of Ip-vementioning

confidence: 99%

Incomplete penetrance and variable expressivity: is there a microRNA connection?

et al. 2009

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Incomplete penetrance and variable expressivity are non‐Mendelian phenomena resulting in the lack of correlation between genotype and phenotype. Not withstanding the diversity in mechanisms, differential expression of homologous alleles within cells manifests as variations in penetrance and expressivity of mutations between individuals of the same genotype. These phenomena are seen most often in dominantly inherited diseases, implying that they are sensitive to concentration of the gene product. In this framework and the advances in understanding the role of microRNA (miRNA) in fine‐tuning gene expression at translational level, we propose miRNA‐mediated regulation as a mechanism for incomplete penetrance and variable expressivity. The presence of miRNA binding sites at 3′ UTR, co‐expression of target gene–miRNA pairs for genes showing incomplete penetrance and variable expressivity derived from available data lend support to our hypothesis. Single nucleotide polymorphisms in the miRNA target site facilitate the implied differential targeting of the transcripts from homologous alleles.

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Variation of the CGG repeat at the fragile X site results in genetic instability: Resolution of the Sherman paradox

Cited by 1,866 publications

References 20 publications

PCR‐amplified microsatellites as markers in plant genetics

PCR‐amplified microsatellites as markers in plant genetics

Intermediate FMR1 alleles and cognitive and/or behavioural phenotypes

Incomplete penetrance and variable expressivity: is there a microRNA connection?

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