Specific transcriptional changes in human fetuses with autosomal trisomies

被引：58

作者：

Altug-Teber, O. ^{[1
]}

Bonin, M. ^{[1
]}

Walter, M. ^{[1
]}

Mau-Holzmann, U. A. ^{[1
]}

Dufke, A. ^{[1
]}

Stappert, H. ^{[1
]}

Tekesin, I. ^{[2
]}

Heilbronner, H. ^{[3
]}

Nieselt, K. ^{[4
]}

Riess, O. ^{[1
]}

机构：

[1] Univ Tubingen, Dept Med Genet, DE-72076 Tubingen, Germany

[2] Univ Tubingen, Dept Gynecol & Obstet, DE-72076 Tubingen, Germany

[3] Inst Clin Genet, Stuttgart, Germany

[4] Ctr Bioinformat, Tubingen, Germany

来源：

CYTOGENETIC AND GENOME RESEARCH | 2007年 / 119卷 / 3-4期

关键词：

DOWN-SYNDROME; CEREBELLAR TRANSCRIPTOME; OVER-EXPRESSION; TS1CJE MOUSE; CHROMOSOME-21; REGION; DOSAGE; GENES; MODEL; DISRUPTION;

D O I：

10.1159/000112058

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Among full autosomal trisomies, only trisomies of chromosome 21 (Down syndrome), 18 (Edwards syndrome) and 13 (Patau syndrome) are compatible with postnatal survival. But the mechanisms, how a supernumerary chromosome disrupts the normal development and causes specific phenotypes, are still not fully explained. As an alternative to gene dosage effect due to the trisomic chromosome a genome-wide transcriptional dysregulation has been postulated. The aim of this study was to define the transcriptional changes in trisomy 13, 18, and 21 during early fetal development in order to obtain more insights into the molecular etiopathology of aneuploidy. Using oligonucleotide microarrays, we analyzed whole genome expression profiles in cultured amniocytes (AC) and chorionic villus cells (CV) from pregnancies with a normal karyotype and with trisomies of human chromosomes 13, 18 and 21. We observed a low to moderate up-regulation for a subset of genes of the trisomic chromosomes. Transcriptional levels of most of the genes on the supernumerary chromosome appeared similar to the respective chromosomal pair in normal karyotypes. A subset of chromosome 21 genes including the DSCR1 gene involved in fetal heart development was consistently up-regulated in different prenatal tissues (AC, CV) of trisomy 21 fetuses whereas only minor changes were found for genes of all other chromosomes. In contrast, in trisomy 18 vigorous downstream transcriptional changes were found. Global transcriptome analysis for autosomal trisomies 13, 18, and 21 supported a combination of the two major hypotheses. Copyright (c) 2008 S. Karger AG, Basel.

引用

页码：171 / 184

页数：14

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