Report of the fourth international workshop on human chromosome 21

Delabar, Jean Maurice; Créau, Nicole; Sinet, P.-M.; Ritter, Otto; Antonarakis, Stylianos E.; Burmeister, Margit; Chakravarti, Aravinda; Nižetić, Dean; Ohki, Masafumi; Patterson, David; Petersen, Michael B.; Reeves, Roger H.; Broeckhoven, Christine Van

doi:10.1016/s0888-7543(05)80390-8

Cited by 29 publications

(4 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The Down Syndrome Candidate Region (DSCR) includes 10% of HC21, spanning the 21q22 region (Korenberg, 1994;Delabar et al 1993;Antonarakis, 1998); its triplication has been shown to be sufficient for the DS phenotype in some subjects. Very little is known about the molecular pathogenesis of Down Syndrome in terms of the contributions of single genes to the DS phenotype.…”

Section: Introductionmentioning

confidence: 99%

Gene Expression Profile Analysis in Human T Lymphocytes from Patients with Down Syndrome

Giannone¹,

Strippoli²,

Vitale³

et al. 2004

Annals of Human Genetics

View full text Add to dashboard Cite

SummaryDown Syndrome (DS) is caused by the presence of three copies of the whole human chromosome 21 (HC21) or of a HC21 restricted region; the phenotype is likely to have originated from the altered expression of genes in the HC21. We apply the cDNA microarray method to the study of gene expression in human T lymphocytes with trisomy 21 in comparison to normal cells.Two patients with DS were investigated, along with two normal subjects as a control, all being tested in independent, duplicated cell culture experiments. The most consistent finding was the overexpression of the superoxide dismutase gene (SOD1), located on 21q, and of MHC DR beta 3 (HLA-DRB3), GABA receptor A gamma 2 (GABRG2), acetyltransferase Coenzyme, A 2 (ACAT2) and ras suppressor protein 1 (RSU1) genes. When the data were clustered according to chromosome localization, the HC21 gene set showed, on average, the highest expression in DS cells in all the experiments. Moreover, separate clustering of patients and controls was obtained when analysis was restricted to HC21 gene expression values.These findings reinforce the specific gene dosage theory for the pathogenesis of the DS phenotype, and show a consistent overexpression of the SOD1 gene on 21q.

show abstract

Section: Introductionmentioning

confidence: 99%

Gene Expression Profile Analysis in Human T Lymphocytes from Patients with Down Syndrome

Giannone¹,

Strippoli²,

Vitale³

et al. 2004

Annals of Human Genetics

View full text Add to dashboard Cite

show abstract

“…A mouse model of DS has long been sought so that the genes contributing to the various features of the phenotype could be determined. There is considerable homology between the routine and the human genomes (Davisson et aL,t990) and mouse Chrl6 has significant similarity to human Chr21, with at least 18 homologous loci (Delabar et aL, 1994;Reeves and Miller, 1992). Trisomy (Ts) for mouse Chrl6 has been a useful model for human Ts21 (Oster-Granite, 1986;Davisson et aL, 1993;Colton et al, 1990;Reeves and Miller, 1992).…”

Section: Introductionmentioning

confidence: 99%

Behavioral assessment of the Ts65Dn mouse, a model for down syndrome: Altered behavior in the elevated plus maze and open field

1996

View full text Add to dashboard Cite

The Ts65Dn mouse carries a partial trisomy for mouse chromosome 16 in a region that has high homology to the Down syndrome (DS) region of human chromosome 21 and is, thus, a potential animal model of DS. The focus of the present study was to begin to characterize the behavioral phenotype of this mouse to assess its usefulness as a model of aspects of the DS phenotype. The behavior of Ts65Dn and littermate control mice was assessed in the elevated plus maze, lighted and dark open field, and a step-down passive avoidance task. The behavior of Ts65Dn mice in these tests differed considerably from the nontrisomic controls. In the elevated plus maze, Ts65Dn had more total arm visits than controls, showed a higher percentage of arm visits to the open arms than control mice, and showed no preference for the closed arms. Ts65Dn mice were more active in both open-field situations, regardless of light condition, and ventured into the center of the arena more than controls. Lighting in the open field had moderate effects on the activity of the Ts65Dn mice, but control mice were, as expected, much more active in the dark than the light. The trisomic mice learned and retained the step-down passive avoidance task in the same number of trials as the controls. Overall, these data indicate that Ts65Dn mice are more active than control mice in two testing situations. Most striking is the finding that the Ts65Dn mice were much less responsive to variations in environmental cues to which normal mice are quite sensitive. These data not only begin to characterize systematically the Ts65Dn phenotype, but also raise several interesting issues about the sources of the aberrant behaviors observed in these mice.

show abstract

“…However, cases are rare and rigorous correlation of trisomic gene content with specific phenotypic features has not been carried out, in particular for cognitive deficits. [13][14][15] Indeed, no significant segment of 21q can be discounted from possibly containing relevant genes. 16 Second, results of large-scale expression experiments comparing trisomic human and mouse tissues to controls generally support the hypothesis of increased mRNA levels due to gene dosage, [17][18][19][20][21][22] although there are gene-and tissue-specific exceptions.…”

Section: Introductionmentioning

confidence: 99%

The cognitive phenotype of Down syndrome: Insights from intracellular network analysis

2006

View full text Add to dashboard Cite

Summary: Down syndrome (DS) is caused by trisomy of chromosome 21. All individuals with DS exhibit some level of cognitive dysfunction. It is generally accepted that these abnormalities are a result of the upregulation of genes encoded by chromosome 21. Many chromosome 21 proteins are known or predicted to function in critical neurological processes, but typically they function as modulators of these processes, not as key regulators. Thus, upregulation in DS is expected to cause only modest perturbations of normal processes. Systematic approaches such as intracellular network construction and analysis have not been generally applied in DS research. Networks can be assembled from highthroughput experiments or by text-mining of experimental literature. We survey some new developments in constructing such networks, focusing on newly developed network analysis methodologies. We propose how these methods could be integrated with creation and manipulation of mouse models of DS to advance our understanding of the perturbed cell signaling pathways in DS. This understanding could lead to potential therapeutics.

show abstract

Report of the fourth international workshop on human chromosome 21

Cited by 29 publications

References 25 publications

Gene Expression Profile Analysis in Human T Lymphocytes from Patients with Down Syndrome

Gene Expression Profile Analysis in Human T Lymphocytes from Patients with Down Syndrome

Behavioral assessment of the Ts65Dn mouse, a model for down syndrome: Altered behavior in the elevated plus maze and open field

The cognitive phenotype of Down syndrome: Insights from intracellular network analysis

Contact Info

Product

Resources

About