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

In order to study genes for a wide variety of research, diagnostic, or therapeutic purposes, scientists use computer programs that analyze DNA sequences. These programs indicate where pieces of genes are located within what is frequently a vast and complex genetic landscape. Although conventional programs detect many parts of genes with ease, they fail when it comes to detecting two important elementsthe very first pieces of genes, and the nearby "on" switches of genes called promoters.

Researchers in the bioinformatics program at Cold Spring Harbor Laboratory have now developed a computer program that is especially good at finding these first segments and "on" switches of genes. The program is tailored toward detecting these features in the human genome sequence, but it will also be useful for annotating other mammalian genomes.

The programcalled "First Exon Finder" or "FirstEF"was developed by Michael Zhang and his colleagues. A paper describing the program is published in the December issue of Nature Genetics.

"FirstEF is the first program that can readily and accurately detect a class of gene segments that has previously been extraordinarily difficult to find," says Zhang. "It's like looking for buried treasure."

The gene segments Zhang is referring to occur at the very beginning of genes, and are called "non-coding first exons." Because they do not encode protein segments, non-coding first exons are undetectable by conventional computer programs that rely on protein coding patterns found in DNA.

Instead, FirstEF recognizes five other DNA "signatures" that betray the presence and location of first exons in genes. The biological basis of some of these telltale genetic signatures is unknown, says Zhang. "But they are real, and perhaps someday biology will explain why they are there." One such signature is the frequency with which two building blocks of DNA, C and G, occur next to each other.

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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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