Developmental defects in trisomy 21 and mouse models.
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TLDR
The main phenotypic alterations occurring during the development of patients with T21 and the developmental abnormalities observed in mouse models are described, and phenotypes common to both species are investigated.Abstract:
Aneuploidies have diverse phenotypic consequences, ranging from mental retardation and developmental abnormalities to susceptibility to common phenotypes and various neoplasms. This review focuses on the developmental defects of murine models of a prototype human aneuploidy: trisomy 21 (Down syndrome, DS, T21). Murine models are clearly the best tool for dissecting the phenotypic consequences of imbalances that affect single genes or chromosome segments. Embryos can be studied freely in mice, making murine models particularly useful for the characterization of developmental abnormalities. This review describes the main phenotypic alterations occurring during the development of patients with T21 and the developmental abnormalities observed in mouse models, and investigates phenotypes common to both species.read more
Citations
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Journal ArticleDOI
Genotype–phenotype correlations in Down syndrome identified by array CGH in 30 cases of partial trisomy and partial monosomy chromosome 21
Robert Lyle,Robert Lyle,Frédérique Béna,Frédérique Béna,Sarantis Gagos,Sarantis Gagos,Corinne Gehrig,Corinne Gehrig,Gipsy Lopez,Gipsy Lopez,Albert Schinzel,James Lespinasse,Armand Bottani,Armand Bottani,Sophie Dahoun,Sophie Dahoun,Laurence Taine,Martine Doco-Fenzy,Pascale Cornillet-Lefèbvre,Anna Pelet,Stanislas Lyonnet,Annick Toutain,Laurence Colleaux,Jürgen Horst,Ingo Kennerknecht,Nobuaki Wakamatsu,Maria Descartes,Judy Franklin,Lina Florentin-Arar,Sophia Kitsiou,Emilie Aït Yahya-Graison,Maher Costantine,Pierre-Marie Sinet,Jean M. Delabar,Stylianos E. Antonarakis,Stylianos E. Antonarakis +35 more
TL;DR: A BAC array spanning HSA21q and array comparative genome hybridization (aCGH) is developed and used to enable high-resolution mapping of pathogenic partial aneuploidies and unbalanced translocations involving HSA 21 to argue against a single DS critical region.
Journal ArticleDOI
DYRK1A and DYRK3 Promote Cell Survival through Phosphorylation and Activation of SIRT1
TL;DR: These findings provide a novel mechanism by which two anti-apoptotic DYRK members promote cell survival through direct modification of SIRT1, an NAD+-dependent protein deacetylase that is essential in a variety of physiological processes including stress response and energy metabolism.
Journal ArticleDOI
Communication breaks-Down: From neurodevelopment defects to cognitive disabilities in Down syndrome
TL;DR: The potential mechanisms by which defects in neurogenesis and neurodegenerative processes lead to altered formation of neural circuits and impair cognitive function are discussed, in connection with findings on pharmacological treatments of potential benefit for DS.
Journal ArticleDOI
Aneuploidy: From a Physiological Mechanism of Variance to Down Syndrome
TL;DR: This review focuses on Down syndrome as the prototype of "genomic disorder" induced by copy number change and the role of genome-altering processes in the generation of diversity in DS neural phenotypes, focusing on the impact of trisomy on brain structure and mental retardation.
Journal ArticleDOI
The Protein Kinase DYRK1A Regulates Caspase-9-Mediated Apoptosis during Retina Development
Ariadna Laguna,Sergi Aranda,Maria Jose Barallobre,R. Barhoum,Eduardo Fernández,Vassiliki Fotaki,Jean-Maurice Delabar,Susana de la Luna,Pedro de la Villa,Maria L. Arbonés +9 more
TL;DR: The data suggest a model in which dysregulation of the apoptotic response in differentiating neurons participates in the neuropathology of diseases that display DYRK1A gene-dosage imbalance effects, such as Down's syndrome.
References
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Journal ArticleDOI
Down syndrome phenotypes: the consequences of chromosomal imbalance
Julie R. Korenberg,Xiao Ning Chen,R. Schipper,Z. Sun,R. Gonsky,S. Gerwehr,N. Carpenter,C. Daumer,P. Dignan,Christine M. Disteche +9 more
TL;DR: Evidence is provided for a significant contribution of genes outside the D21S55 region to the DS phenotypes, including the facies, microcephaly, short stature, hypotonia, abnormal dermatoglyphics, and mental retardation, which strongly suggests DS is a contiguous gene syndrome and augurs against a single DS chromosomal region responsible for most of the phenotypic features.
Journal Article
Study of somatic chromosomes from 9 mongoloid children
Journal ArticleDOI
NFAT dysregulation by increased dosage of DSCR1 and DYRK1A on chromosome 21
Joseph R. Arron,Monte M. Winslow,Alberto Polleri,Ching Pin Chang,Hai Wu,Xin Gao,Joel R. Neilson,Lei Chen,Jeremy J Heit,Seung K. Kim,Nobuyuki Yamasaki,Tsuyoshi Miyakawa,Uta Francke,Isabella A. Graef,Gerald R. Crabtree +14 more
TL;DR: It is suggested that the 1.5-fold increase in dosage of DSCR1 and DYRK1A cooperatively destabilizes a regulatory circuit, leading to reduced NFATc activity and many of the features of Down's syndrome, and the destabilization of regulatory circuits can underlie human disease.
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Chromosome 21 and down syndrome: from genomics to pathophysiology.
Stylianos E. Antonarakis,Robert Lyle,Emmanouil T. Dermitzakis,Alexandre Reymond,Samuel Deutsch +4 more
TL;DR: Comparative genomics is beginning to identify the functional components of the chromosome and that in turn will set the stage for the functional characterization of the sequences.
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