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Vol. 11, Issue 6, 1053-1070, June 2001

LETTER
Analysis of the Cat Eye Syndrome Critical Region in Humans and the Region of Conserved Synteny in Mice: A Search for Candidate Genes at or near the Human Chromosome 22 Pericentromere

Tim K. Footz,1,5 Polly Brinkman-Mills,1,5 Graham S. Banting,1,5 Stephanie A. Maier,1 M. Ali Riazi,1 Lindsay Bridgland,1 Song Hu,1 Bruce Birren,2 Shinsei Minoshima,3 Nobuyoshi Shimizu,3 HuaQin Pan,4 Thuan Nguyen,4 Fang Fang,4 Ying Fu,4 Linda Ray,4 Hui Wu,4 Steve Shaull,4 Stacey Phan,4 Ziyun Yao,4 Feng Chen,4 Axin Huan,4 Ping Hu,4 Qiaoyan Wang,4 Phoebe Loh,4 Sulan Qi,4 Bruce A. Roe,4 and Heather E. McDermid1,6

1 Department of Biological Sciences, University of Alberta, Edmonton, Alberta T6G 2E9, Canada; 2 Whitehead Institute/MIT Center for Genome Research, Cambridge, Massachusetts 02141, USA; 3 Department of Molecular Biology, Keio University School of Medicine, Tokyo 160-8582, Japan; 4 Department of Chemistry and Biochemistry, University of Oklahoma, Norman, Oklahoma 73019-0370, USA

We have sequenced a 1.1-Mb region of human chromosome 22q containing the dosage-sensitive gene(s) responsible for cat eye syndrome (CES) as well as the 450-kb homologous region on mouse chromosome 6. Fourteen putative genes were identified within or adjacent to the human CES critical region (CESCR), including three known genes (IL-17R, ATP6E, and BID) and nine novel genes, based on EST identity. Two putative genes (CECR3 and CECR9) were identified, in the absence of EST hits, by comparing segments of human and mouse genomic sequence around two solitary amplified exons, thus showing the utility of comparative genomic sequence analysis in identifying transcripts. Of the 14 genes, 10 were confirmed to be present in the mouse genomic sequence in the same order and orientation as in human. Absent from the mouse region of conserved synteny are CECR1, a promising CES candidate gene from the center of the contig, neighboring CECR4, and CECR7 and CECR8, which are located in the gene-poor proximal 400 kb of the contig. This latter proximal region, located ~1 Mb from the centromere, shows abundant duplicated gene fragments typical of pericentromeric DNA. The margin of this region also delineates the boundary of conserved synteny between the CESCR and mouse chromosome 6. Because the proximal CESCR appears abundant in duplicated segments and, therefore, is likely to be gene poor, we consider the putative genes identified in the distal CESCR to represent the majority of candidate genes for involvement in CES.

5 These authors contributed equally to this work.

6 Corresponding author.

11:1053-1070 ©2001 by Cold Spring Harbor Laboratory Press  ISSN 1088-9051/01 $5.00
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