Journal ArticleDOI
Inherited microdeletions in the Angelman and Prader-Willi syndromes define an imprinting centre on human chromosome 15.
Karin Buiting,Shinji Saitoh,Shinji Saitoh,Stephanie Gross,Bärbel Dittrich,Stuart Schwartz,Stuart Schwartz,Robert D. Nicholls,Robert D. Nicholls,Bernhard Horsthemke +9 more
TLDR
A subset of patients with Angelman and Prader–Willi syndrome have apparently normal chromosomes of biparental origin, but abnormal DMA methylation at several loci within chromosome 15q11–13, and probably have a defect in imprinting.Abstract:
A subset of patients with Angelman and Prader-Willi syndrome have apparently normal chromosomes of biparental origin, but abnormal DNA methylation at several loci within chromosome 15q11-13, and probably have a defect in imprinting. Using probes from a newly established 160-kb contig including D15S63 (PW71) and SNRPN, we have identified inherited microdeletions in two AS families and three PWS families. The deletions probably affect a single genetic element that we term the 15q11-13 imprinting centre (IC). In our model, the IC regulates the chromatin structure, DNA methylation and gene expression in cis throughout 15q11-13. Mutations of the imprinting centre can be transmitted silently through the germline of one sex, but appear to block the resetting of the imprint in the germline of the opposite sex.read more
Citations
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Genomic imprinting: parental influence on the genome
TL;DR: The study of imprinting provides new insights into epigenetic gene modification during development, and is thought to influence the transfer of nutrients to the fetus and the newborn from the mother.
Journal ArticleDOI
Prader-Willi syndrome
TL;DR: Prader-Willi syndrome is characterized by severe infantile hypotonia with poor suck and failure to thrive; hypogonadism causing genital hypoplasia and pubertal insufficiency; characteristic facial features; early-childhood onset obesity and hyperphagia; developmental delay/mild intellectual disability; short stature; and a distinctive behavioral phenotype.
Journal ArticleDOI
UBE3A/E6-AP mutations cause Angelman syndrome
TL;DR: It is demonstrated that UBE3A mutations are one cause of AS and indicate a possible abnormality in ubiquitin-mediated protein degradation during brain development in this disease.
Journal ArticleDOI
De novo truncating mutations in E6-AP ubiquitin-protein ligase gene (UBE3A) in Angelman syndrome.
Toshinobu Matsuura,James S. Sutcliffe,Ping Fang,Robert-Jan Galjaard,Yong-hui Jiang,Claudia S. Benton,Johanna M. Rommens,Arthur L. Beaudet +7 more
TL;DR: Intragenic mutation of UBE3A in AS is the first examples of a genetic disorder of the ubiquitin-dependent proteolytic pathway in mammals and may represent an example of a human genetic disorder associated with a locus producing functionally distinct imprinted and biallelically expressed gene products.
Journal ArticleDOI
Mutation of the angelman ubiquitin ligase in mice causes increased cytoplasmic p53 and deficits of contextual learning and long-term potentiation
Yong-hui Jiang,Dawna L. Armstrong,Urs Albrecht,Coleen M. Atkins,Jeffrey L. Noebels,Gregor Eichele,J. D. Sweatt,Arthur L. Beaudet,Arthur L. Beaudet +8 more
TL;DR: The cytoplasmic abundance of p53 was increased in postmitotic neurons in m-/p+ mice and in AS, providing a potential biochemical basis for the phenotype through failure to ubiquitinate and degrade various effectors.
References
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Journal ArticleDOI
Deletions of a differentially methylated CpG island at the SNRPN gene define a putative imprinting control region
James S. Sutcliffe,Mitsuyoshi Nakao,Susan L. Christian,Karen Helene Ørstavik,Niels Tommerup,David H. Ledbetter,Arthur L. Beaudet +6 more
TL;DR: The authors' data imply the presence of a paternal imprinting control region near exon α of SNRPN, which would imply the molecular basis of Prader-Willi syndrome and Angelman syndrome.
Journal ArticleDOI
Allele-specific replication timing of imprinted gene regions
Daniel Kitsberg,S. Selig,Michael Brandeis,Itamar Simon,Ilana Keshet,Daniel J. Driscoll,Robert D. Nicholls,Howard Cedar +7 more
TL;DR: Examination of replication timing patterns for the chromosomal regions containing the imprinted genes Igf2, Igf 2r, H19 and Snrpn in the mouse reveals that the two homologous alleles replicate asynchronously and it is always the paternal allele that is early-replicating.
Journal ArticleDOI
Recombination at the human α-globin gene cluster: Sequence features and topological constraints
TL;DR: The sizes of these deletions, the nonrandom distribution of their breakpoints, and the nature of the inversion-duplication transposition event suggest that these rearrangements are constrained by the higher-order structure of the α-globin cluster.
Journal ArticleDOI
Methylation and imprinting: from host defense to gene regulation?
TL;DR: Genetic imprinting causes the expression of a gene to vary according to its maternal or paternal origin, and the raison d'etre of imprinting is unclear.