Gene Expression Profile of Human Down Syndrome Leukocytes

Malagó Jr., Wilson; Sommer, César A.; Del Cistia Andrade, Camillo; Soares-Costa, Andrea; Possik, Patrícia Abrao; Cassago, Alexandre; Silveira, Henrique C. Santejo; Henrique-Silva, Flávio
August 2005
Croatian Medical Journal;2005, Vol. 46 Issue 4, p647
Academic Journal
Aim 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. Conclusion 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.


Related Articles

  • Trisomy 21 and Down syndrome - A short review. Sommer, C. A.; Henrique-Silva, F. // Brazilian Journal of Biology;May2008, Vol. 68 Issue 2, p447 

    Even though the molecular mechanisms underlying the Down syndrome (DS) phenotypes remain obscure, the characterization of the genes and conserved non-genic sequences of HSA21 together with large-scale gene expression studies in DS tissues are enhancing our understanding of this complex disorder....

  • Trisomic and Allelic Differences Influence Phenotypic Variability During Development of Down Syndrome Mice. Deitz, Samantha L.; Roper, Randall J. // Genetics;Dec2011, Vol. 189 Issue 4, p1487 

    Individuals with full or partial Trisomy 21 (Ts21) present with clinical features collectively referred to as Down syndrome (DS), although DS phenotypes vary in incidence and severity between individuals. Differing genetic and phenotypic content in individuals with DS as well as mouse models of...

  • Heart morphogenesis is not affected by overexpression of the Sh3bgr gene mapping to the Down syndrome heart critical region. Sandri, Claudia; Di Lisi, Raffaella; Picard, Anne; Argentini, Carla; Calabria, Elisa; Myklak, Kristene; Scartezzini, Paolo; Schiaffino, Stefano // Human Genetics;Apr2004, Vol. 114 Issue 5, p517 

    Congenital heart disease (CHD) is the most common birth defect in humans and is present in 40% of newborns affected by Down syndrome (DS). The SH3BGR gene maps to the DS-CHD region and is a potential candidate for the pathogenesis of CHD, since it is selectively expressed in cardiac and skeletal...

  • Altered expression of hypothetical proteins in hippocampus of transgenic mice overexpressing human Cu/Zn-superoxide dismutase I. Joo-Ho Shin; Jae-Won Yang; Le Pecheur, Marie; London, Jacqueline; Hoeger, Harald; Lubec, Gert // Proteome Science;2004, Vol. 2, p2 

    Background: Cu/Zn-superoxide dismutase 1 (SOD1), encoded on chromosome 21, is a key enzyme in the metabolism of reactive oxygen species (ROS) and pathogenetically relevant for several disease states including Down syndrome (DS; trisomy 21). Systematically studying protein expression in human...

  • GATA1, Cytidine Deaminase, and the High Cure Rate of Down Syndrome. Ge, Yubin; Stout, Mark L.; Tatman, Dana A.; Jensen, Tanya L.; Buck, Steven A.; Thomas, Ronald L.; Ravindranath, Yaddanapudi; Matherly, Larry H.; Taub, Jeffrey W. // JNCI: Journal of the National Cancer Institute;2/2/2005, Vol. 97 Issue 3, p226 

    Down syndrome children with acute megakaryocytic leukemia (AMkl,) have higher cure rates than non-Down syndrome acute myeloid leukemia (AML) patients treated with cytosine arabinoside (ara-C). Megakaryoblasts from Down syndrome AML patients are more sensitive in vitro to ara-C than cells from...

  • Living It Down. Schmitt, Adam // Teen Ink;Jan2009, Vol. 20 Issue 5, p28 

    The author describes how difficult life is for people inflicted with Down syndrome.

  • 2q23.1 microdeletion identified by array comparative genomic hybridisation: an emerging phenotype with Angelman-like features?  // Journal of Medical Genetics;Dec2009, Vol. 46 Issue 12, p8 

    Background: Genome-wide screening of patients with mental retardation using array comparative genomic hybridisation (CGH) has identified several novel imbalances. With this genotype-first approach, the 2q22.3q23.3-deletion was recently described as a novel microdeletion syndrome. The authors...

  • DNA damage studies in cases of Trisomy 21 using Comet Assay. Jayaprakash, T.; Rao, K. Ramachandra; Bhat, B. Vishnu; Chand, Parkash; Kumar, S. Nandha // Current Pediatric Research;Jan2010, Vol. 14 Issue 1, p1 

    Objective: To study the DNA damage levels among the cases of Down's syndrome(DS) with that of the age and sex matched controls using single cell gel eleetrophoresis (SCGE) or Comet assay. Methods: Phytohaemagglutinin stimulated lymphocyte cell culture was car-ried out using RPMI 1640. G banded...

  • Alzheimer's Disease Amyloid-β Links Lens and Brain Pathology in Down Syndrome. Moncaster, Juliet A.; Pineda, Roberto; Moir, Robert D.; Suqian Lu; Burton, Mark A.; Ghosh, Joy G.; Ericsson, Maria; Soscia, Stephanie J.; Mocofanescu, Anca; Folkerth, Rebecca D.; Robb, Richard M.; Kuszak, Jer R.; Clark, John I.; Tanzi, Rudolph E.; Hunter, David G.; Goldstein, Lee E. // PLoS ONE;2010, Vol. 5 Issue 5, p1 

    Down syndrome (DS, trisomy 21) is the most common chromosomal disorder and the leading genetic cause of intellectual disability in humans. In DS, triplication of chromosome 21 invariably includes the APP gene (21q21) encoding the Alzheimer's disease (AD) amyloid precursor protein (APP)....


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics