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Vol. 11, Issue 11, 1935-1943, November 2001

METHODS
Automated Construction of High-Density Comparative Maps Between Rat, Human, and Mouse

Anne E. Kwitek,1,3,8 Peter J. Tonellato,2,3 Dan Chen,2 Jo Gullings-Handley,1 Yongjian Samuel Cheng,2 Simon Twigger,2,3 Todd E. Scheetz,4,5,6 Thomas L. Casavant,7 Monika Stoll,1,3 Marcelo A. Nobrega,1,3 Masahide Shiozawa,1,3 M. Bento Soares,5,6 Val C. Sheffield,4,5 and Howard J. Jacob1,3

1 Human and Molecular Genetics Center, 2 Bioinformatics Research Center, and 3 Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA; 4 Howard Hughes Medical Institute and Departments of 5 Pediatrics, 6 Physiology and Biophysics, and 7 Electrical and Computer Engineering, The University of Iowa, Iowa City, Iowa 52242, USA

Animal models have been used primarily as surrogates for humans, having similar disease-based phenotypes. Genomic organization also tends to be conserved between species, leading to the generation of comparative genome maps. The emergence of radiation hybrid (RH) maps, coupled with the large numbers of available Expressed Sequence Tags (ESTs), has revolutionized the way comparative maps can be built. We used publicly available rat, mouse, and human data to identify genes and ESTs with interspecies sequence identity (homology), identified their UniGene relationships, and incorporated their RH map positions to build integrated comparative maps with >2100 homologous UniGenes mapped in more than one species (~6% of all mammalian genes). The generation of these maps is iterative and labor intensive; therefore, we developed a series of computer tools (not described here) based on our algorithm that identifies anchors between species and produces printable and on-line clickable comparative maps that link to a wide variety of useful tools and databases. The maps were constructed using sequence-based comparisons, thus creating "hooks" for further sequence-based annotation of human, mouse, and rat sequences. Currently, this map enables investigators to link the physiology of the rat with the genetics of the mouse and the clinical significance of the human.

8 Corresponding author.

11:1935-1943 ©2001 by Cold Spring Harbor Laboratory Press  ISSN 1088-9051/01 $5.00
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