Hum. Reprod. Advance Access published online on July 17, 2007
Human Reproduction, doi:10.1093/humrep/dem214
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Genome-wide expression analysis of cultured trophoblast with trisomy 21 karyotype
1 Department of Internal Medicine ‘T’, Tel Aviv Sourasky Medical Center, Tel Aviv 64239, Israel 2 Genetic Department, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel 3 Prenatal Diagnosis Unit, Genetic Institute, Tel Aviv Sourasky Medical Center, 6 Weizmann Street, Tel Aviv 64239, Israel 4 Lis Maternity Hospital, Tel Aviv Sourasky Medical Center, Tel Aviv 64239, Israel
5 Correspondence address. Prenatal Diagnosis Unit, Genetic Institute, Tel Aviv Sourasky Medical Center, 6 Weizmann Street, Tel Aviv 64239, Israel. Tel: +972-3-6973921; Fax: +972-3-6974555; E-mail: yyaron{at}tasmc.health.gov.il
BACKGROUND: The pathologic features of Down syndrome are assumed to be the result of over-expression of genes located on chromosome 21 and/or a more global transcriptional misregulation that crosses chromosomal borders.
METHODS: To address this issue, four RNA samples from trisomy 21 placentas and four samples from normal first trimester pregnancies were analyzed using Affymetrix U95v2 microarray. Statistical and bioinformatic analyses were employed to compare global gene expression, functional classes, and pathways to differentiate between placentas taken from trisomy 21 and from normal pregnancies.
RESULTS: About 750 genes were significantly over-expressed in trisomy 21. This list contains an 
4.5-fold over-abundance of genes that map to chromosome 21, compared to that which could be expected for this chromosome, on the microarray. Among the classes of genes that best discriminated the trisomy 21 and normal karyotype, we found genes that are also implicated in Alzheimer disease and genes that are associated with ubiquitination and proteosomal degradation. Finally, using the top 10 most discriminating genes, eight samples taken from a different database were correctly classified as either trisomy 21 or normal.
CONCLUSIONS: Our results demonstrate that gene expression in trisomy 21 affected placentas significantly differs from that of chromosomally normal placentas, and this difference is only partially explained by over-expression of genes from chromosome 21. Our findings suggest that specific highly discriminatory genes may be potential targets for further research and development of novel prenatal diagnosis techniques.
Key words: trisomy 21/gene-expression/microarray/bioinformatics/CVS
Submitted on January 18, 2007; resubmitted on June 10, 2007; accepted on June 15, 2007.
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