Gene expression profile of human Down syndrome leukocytes.
OBJECTIVE
Identification of differences in the gene expression patterns of Down syndrome and normal leukocytes.


METHODS
We constructed the first Down syndrome leukocyte serial analysis of gene expression (SAGE) library from a 28 year-old patient. This library was analyzed and compared with a normal leukocyte SAGE library using the eSAGE software. Reverse transcriptase polymerase chain reaction (RT-PCR) was used to validate the results.


RESULTS
We found that a large number of unidentified transcripts were overexpressed in Down syndrome leukocytes and some transcripts coding for growth factors (e.g. interleukin 8, IL-8), ribosomaproteins (e.g. L13a, L29, and L37), and transcription factors (e.g., Jun B, Jun D, and C/EBP beta) were underexpressed. The SAGE data were successfully validated for the genes IL-8, CXCR4, BCL2A1, L13a, L29, L37, and GTF3A using RT-PCR.


CONCLUSIONS
Our analysis identified significant changes in the expression pattern of Down syndrome leukocytes compared with normal ones, including key regulators of growth and proliferation, ribosomal proteins, and a large number of overexpressed transcripts that were not matched in UniGene clusters and that may represent novel genes related to Down syndrome. This study offers a new insight into transcriptional changes in Down syndrome leukocytes and indicates candidate genes for further investigations into the molecular mechanism of Down syndrome pathology.
Malagó
Wilson
W
Department of Genetics and Evolution, Federal University of Sao Carlos, Rodovia Washington Luis, Km 235, CEP 13565-905, Sao Carlos, SP, Brazil.
Sommer
César A
CA
Del Cistia Andrade
Camillo
C
Soares-Costa
Andrea
A
Abrao Possik
Patricia
P
Cassago
Alexandre
A
Santejo Silveira
Henrique C
HC
Henrique-Silva
Flavio
F
D000328:Adult; D001483:Base Sequence; D017931:DNA Primers; D004314:Down Syndrome / Q000097:blood / Q000235:genetics*; D020869:Gene Expression Profiling; D006801:Humans; D007962:Leukocytes / Q000378:metabolism*; D008297:Male; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017931:DNA Primers