Journal ArticleDOI
Length of uninterrupted CGG repeats determines instability in the FMR1 gene.
Evan E. Eichler,Jeanette J. A. Holden,Bradley W. Popovich,Allan L. Reiss,Karen Snow,Stephen N. Thibodeau,C. Sue Richards,Patricia A. Ward,David L. Nelson +8 more
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TLDR
Analysis of 84 human X chromosomes for the presence of interrupting AGG trinucleotides within the CGG repeat tract of the FMR1 gene revealed that most alleles possess two interspersed AGGs and that the longest tract of uninterrupted CGG repeats is usually found at the 3′ end.Abstract:
Analysis of 84 human X chromosomes for the presence of interrupting AGG trinucleotides within the CGG repeat tract of the FMR1 gene revealed that most alleles possess two interspersed AGGs and that the longest tract of uninterrupted CGG repeats is usually found at the 3' end. Variation in the length of the repeat appears polar. Alleles containing between 34 and 55 repeats, with documented unstable transmissions, were shown to have lost one or both AGG interruptions. These comparisons define an instability threshold of 34-38 uninterrupted CGG repeats. Analysis of premutation alleles in Fragile X syndrome carriers reveals that 70% of these alleles contain a single AGG interruption. These data suggest that the loss of an AGG is an important mutational event in the generation of unstable alleles predisposed to the Fragile X syndrome.read more
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Journal ArticleDOI
Fine-scale structural variation of the human genome.
Eray Tüzün,Andrew J. Sharp,Jeffrey A. Bailey,Rajinder Kaul,V. Anne Morrison,Lisa M. Pertz,Eric Haugen,Hillary S. Hayden,Donna G. Albertson,Daniel Pinkel,Maynard V. Olson,Evan E. Eichler +11 more
TL;DR: This work systematically compared the human genome reference sequence with a second genome to detect intermediate-sized structural variants >8 kb in length and validated 112 of the structural variants, including several that are of biomedical relevance.
Journal ArticleDOI
Cloning of the gene for spinocerebellar ataxia 2 reveals a locus with high sensitivity to expanded CAG/glutamine repeats
Georges Imbert,Frédéric Saudou,Frédéric Saudou,Gaël Yvert,Gaël Yvert,Didier Devys,Didier Devys,Yvon Trottier,Yvon Trottier,Jean-Marie Garnier,Jean-Marie Garnier,Chantal Weber,Chantal Weber,Jean-Louis Mandel,Jean-Louis Mandel,Géraldine Cancel,Géraldine Cancel,Nacer Abbas,Nacer Abbas,Alexandra Durr,Alexandra Durr,Olivier Didierjean,Olivier Didierjean,Giovanni Stevanin,Giovanni Stevanin,Yves Agid,Yves Agid,Alexis Brice,Alexis Brice +28 more
TL;DR: The steep inverse correlation between age of onset and CAG number suggests a higher sensitivity to polyglutamine length than in the other polyglUTamine expansion diseases.
Journal ArticleDOI
A decade of molecular studies of fragile X syndrome.
TL;DR: Analysis of synapse abnormalities in patients and Fmr1 knockout mice should prove useful in studying the pathogenesis of fragile X syndrome and understanding learning and cognition in general.
Journal ArticleDOI
Trinucleotide repeat expansion and human disease
TL;DR: Eleven human loci, responsible for nine diseases, exhibit an unprecedented form of mutation: the expansion of trinucleotide repeats, which explains the genetic anticipation in these disorders.
Journal ArticleDOI
An Empirical Evaluation of Genetic Distance Statistics Using Microsatellite Data From Bear (Ursidae) Populations
TL;DR: A large microsatellite data set from three species of bear (Ursidae) was used to empirically test the performance of six genetic distance measures in resolving relationships at a variety of scales ranging from adjacent areas in a continuous distribution to species that diverged several million years ago as discussed by the authors.
References
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Journal ArticleDOI
Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome
Annemiske J.M.H. Verkerk,Maura Pieretti,James S. Sutcliffe,Ying-Hui Fu,Derek P.A. Kuhl,Antonio Pizzuti,Orly Reiner,Stephen Richards,Maureen F. Victoria,Fuping Zhang,Bert Eussen,Gert-Jan B. van Ommen,Lau Blonden,Gregory J. Riggins,Jane L. Chastain,Catherine B. Kunst,Hans Galjaard,C. Thomas Caskey,David L. Nelson,Ben A. Oostra,Stephen T. Warren +20 more
TL;DR: A fragile X site-induced breakpoint cluster region that exhibits length variation in fragile X chromosomes is identified and localization of the brain-expressed FMR-1 gene to this EcoRI fragment suggests the involvement of this gene in the phenotypic expression of the fragile X syndrome.
Journal ArticleDOI
Microsatellite instability in cancer of the proximal colon
TL;DR: Colorectal tumor DNA was examined for somatic instability at (CA)n repeats on human chromosomes 5q, 15q, 17p, and 18q, and this instability was significantly correlated with the tumor's location in the proximal colon and with increased patient survival and loss of heterozygosity.
Journal ArticleDOI
Slipped-strand mispairing: a major mechanism for DNA sequence evolution.
G Levinson,George A. Gutman +1 more
TL;DR: Evidence is presented that single-base repeats (the shortest possible motifs) are represented by longer runs in mammalian introns than would be expected on a random basis, supporting the idea that SSM may be a ubiquitous force in the evolution of the eukaryotic genome.
Journal ArticleDOI
Variation of the CGG repeat at the fragile X site results in genetic instability: resolution of the Sherman paradox.
Ying-Hui Fu,Derek P.A. Kuhl,Antonio Pizzuti,Maura Pieretti,James S. Sutcliffe,James S. Sutcliffe,Stephen Richards,Annemieke J.M.H. Verkert,Jeanette J. A. Holden,Raymond G. Fenwick,Stephen T. Warren,Stephen T. Warren,Ben A. Oostra,David L. Nelson,C. Thomas Caskey +14 more
TL;DR: The risk of expansion during oogenesis to the full mutation associated with mental retardation increases with the number of repeats, and this variation in risk accounts for the Sherman paradox.
Journal ArticleDOI
Instability of a 550-base pair DNA segment and abnormal methylation in fragile X syndrome
I. Oberlé,François Rousseau,Dominique Heitz,Christine Kretz,Didier Devys,André Hanauer,Joëlle Boué,Bertheas Mf,Jean-Louis Mandel +8 more
TL;DR: expression of the fragile X syndrome appears to result from a two-step mutation as well as a highly localized methylation, and can easily be detected regardless of sex or phenotypic expression.
Related Papers (5)
Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome
Annemiske J.M.H. Verkerk,Maura Pieretti,James S. Sutcliffe,Ying-Hui Fu,Derek P.A. Kuhl,Antonio Pizzuti,Orly Reiner,Stephen Richards,Maureen F. Victoria,Fuping Zhang,Bert Eussen,Gert-Jan B. van Ommen,Lau Blonden,Gregory J. Riggins,Jane L. Chastain,Catherine B. Kunst,Hans Galjaard,C. Thomas Caskey,David L. Nelson,Ben A. Oostra,Stephen T. Warren +20 more