J Mol Cell Cardiol 33, 587–591 (2001) doi:10.1006/jmcc.2000.1335, available online at http://www.idealibrary.com on Rapid Communication Organization of Human Cardiovascular- expressed Genes on Chromosomes 21 and 22 Adam A. Dempsey 1,2 , Noel Pabalan 2 , HongChang Tang 2 and Choong-Chin Liew 1,2 1 The Cardiovascular Genome Unit, Brigham and Women’s Hospital, 75 Francis Street, Thorn 1326; Harvard Medical School, Boston, MA 02115, USA; 2 Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario M5G1L5, Canada (Received 19 December 2000, accepted 19 December 2000, published electronically 24 January 2001) A. A. D , N. P, HC. T   C.-C. L. Organization of Human Cardiovascular-expressed Genes on Chromosomes 21 and 22. Journal of Molecular and Cellular Cardiology (2001) 33, 587–591. The recent availability of the sequenced and annotated DNA sequences of chromosomes 21 and 22 has initiated the next phase in the human genome project: the application of this resource. One facet of these data is that they provide a list of ordered genes along the chromosome that can be capitalized upon to determine gene position effects. Specifically, the physical position and distribution of genes along the chromosomes may be related to gene expression in specific organs or organ systems. In this report we index the subset of genes constituting the human “cardiovascular genome” on chromosomes 21q and 22q as well as report the identification of several “cardiovascular gene” clusters. These gene clusters are suggestive of a higher order of tissue-specific gene regulation at the chromosomal level.  2001 Academic Press K W: Chromosome gene density; Chromosome remodeling; Cardiovascular Expressed Sequence Tags (ESTs); Cardiovascular genomics. profile data generated from oligonucleotide mi- Introduction croarrays from yeast at various stages in the cell cycle indicated that genes positioned next to each Current evidence supports the hypothesis that chro- matin structure participates in gene regulation and other have a high probability of being co-regulated. 7 In order to explore this concept, we took ad- the use of further dynamic chromatin remodelling as a biological strategy to regulate gene tran- vantage of the recently completed and annotated DNA sequences of human chromosome 21 (C21) scription. 1–3 This is especially important when ex- tensive phenotypic changes occur during processes and 22 (C22). 8,9 Through sequence similarity searching of our current human cardiovascular- such as cell differentiation and ontogenesis as chro- matin remodelling has been shown to regulate based Expressed Sequence Tag (EST) database (cv- EST) housing 111224 ESTs with all 223 and 545 gene expression in a temporal- and tissue-specific manner. 4–6 If chromatin structure plays a role in transcript-encoding genes located on C21q and C22q, respectively, we were able to determine which the transcriptional regulation of genes during de- velopment, it is possible the physical distribution of of these genes were expressed in the cardiovascular system (CVS). 10,11 We identified at least 100 (44.8%) genes along the chromosomes may have a higher order of organization than currently envisaged. In and 248 (45.5%) genes on the q-arms of C21 and C22, respectively, that are expressed in the CVS. support of this, a recent report using gene expression Please address all correspondence to: Dr C. C. Liew, The Cardiovascular Genome Unit, Brigham and Women’s Hospital, 75 Francis Street, Thorn 1326; Harvard Medical School, Boston, MA 02115, USA. E-mail: cliew@rics.bwh.harvard.edu 0022–2828/01/030587+05 $35.00/0  2001 Academic Press