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New computer program detects overlooked gene segments: Previous estimates of human gene number too low

hey do not encode protein, non-coding first exons are essential components of gene structure and function. Consequently, the ability to detect non-coding first exons is crucial for scientists wishing to study genes for a wide variety of biological and biomedical applications.

"The results Michael Zhang is getting with FirstEF are very exciting," says James Kent, a graduate student at the University of California at Santa Cruz. Kent's own computer program called "GigAssembler" caused a sensation in the world of genome research when he used it to generate the first and only publicly-available assembly of the human genome sequence in June of last year. Kent hopes to add a FirstEF "track" to the Human Genome Browser he has created (available at http://genome.ucsc.edu).

When Zhang used FirstEF to analyze the DNA sequences of human chromosomes 21 and 22, he found that the program correctly pinpointed the location of 90 percent of known first exons on those chromosomes. According to Zhang, FirstEF was nearly twice as sensitive as a program available from DoubleTwist, Inc. and Genomatix Software GmbH called "PromoterInspector." Zhang was joined in this study by postdoctoral researchers Ramana Davuluri (now on the faculty at Ohio State University) and Ivo Grosse.

Later, Zhang and his colleagues used FirstEF to analyze the entire human genome. They identified some 68,000 first exons. This result does not necessarily mean that there are 68,000 or so human genes, because a single gene can use alternative first exons. Moreover, the total number of genes in an organism's genome depends on other, subtle definitions of what constitutes a gene. Nevertheless, Zhang believes there are 50 to 60,000 human genes and that previous estimates of 30 to 40,000 human genes are too low.

One bonus of the way FirstEF operates is that it identifies not only first exons of genes, but also the "on" switches of genes called "promot
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Contact: Peter W. Sherwood
sherwood@cshl.org
516-367-6947
Cold Spring Harbor Laboratory
28-Nov-2001


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