Genomic sequence comparison of the human and mouse adenosine deaminase gene regions |
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Authors: | Anthony G Brickner Ben F Koop Bruce J Aronow Dan A Wiginton |
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Institution: | (1) Department of Pediatrics, Division of Developmental Biology, University of Cincinnati College of Medicine and Children's Hospital Research Foundation, Cincinnati, Ohio 45229, USA, US;(2) Center for Environmental Health-Biology, University of Victoria, Victoria, BC, Canada V8W-272, CA |
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Abstract: | A challenge for mammalian genetics is the recognition of critical regulatory regions in primary gene sequence. One approach
to this problem is to compare sequences from genes exhibiting highly conserved expression patterns in disparate organisms.
Previous transgenic and transfection analyses defined conserved regulatory domains in the mouse and human adenosine deaminase
(ADA) genes. We have thus attempted to identify regions with comparable similarity levels potentially indicative of critical
ADA regulatory regions. On the basis of aligned regions of the mouse and human ADA gene, using a 24-bp window, we find that
similarity overall (67.7%) and throughout the noncoding sequences (67.1%) is markedly lower than that of the coding regions
(81%). This low overall similarity facilitated recognition of more highly conserved regions. In addition to the highly conserved
exons, ten noncoding regions >100 bp in length displayed >70% sequence similarity. Most of these contained numerous 24-bp
windows with much higher levels of similarity. A number of these regions, including the promoter and the thymic enhancer,
were more similar than several exons. A third block, located near the thymic enhancer but just outside of a minimally defined
locus control region, exhibited stronger similarity than the promoter or thymic enhancer. In contrast, only fragmentary similarity
was exhibited in a region that harbors a strong duodenal enhancer in the human gene. These studies show that comparative sequence
analysis can be a powerful tool for identifying conserved regulatory domains, but that some conserved sequences may not be
detected by certain functional analyses as transgenic mice.
Received: 27 March 1998 / Accepted: 22 September 1998 |
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