Some travel to Everest. Some visit the bottom of the ocean. Anda few lucky explorers have even made it to the moon. But CraigVenter has been having just as much fun in his own laboratory,exploring the genome. His recent discoveries are helpingscientists to determine the functions of genes.

It was drudgery that drove Venter to advance the science ofsequencing, and to establish his Institute for Genomic Research,based in Gaithersburg, Md., he told the audience at the FirstInternational Conference of Nature Genetics. "I didn't want tospend another decade purifying another protein," he said.When he heard about automated sequencing, he decided hehad to have it.

Automated sequencing had done wonders for genome research,but there was so much to do, and it had its own tedium.Desperate for understanding of what sequence meant, Venterand his colleagues tried sequencing randomly picked cDNAs.

"We didn't think this was interesting until we started findinggenes in the brain of a 2-year-old female that were identical togenes that others had sequenced from testes and bone," hesaid. At first they thought their assay was inaccurate, but then,"a more interesting set of things came out of the new braincDNA sequence that were closely related to sequences fromother species."

Soon, the strange became ordinary. "It's not surprising wefound genes in the human brain whose closest match is barley,"Venter said.

In fact, 20 percent of genes from a yeast have counterparts inthe human brain, which motivated Venter to characterize theyeast genome, a project he expects to complete this summer."We think this will be helpful to understanding genes fromevery organ and tissue."

At the institute, he said, "we are generating 250,000 to 500,000base pairs of human sequence each day."

Venter proceeded to show slides of new ion channels,oncogenes, an olfactory-like receptor from a fetal lung thatmatched a testicular gene, and plenty of other genetic wonders.

Another highlight of the conference was an exploration of thegenetics of cancer. Kenneth Kinzler, professor of oncology at theJohns Hopkins University Oncology Center, described thecascade of mutations that leads to colorectal cancer,culminating in the loss of the p53 gene on chromosome 17. Hefocused on the APC gene, which, when defective, causes familialadenomatous polyposis (FAP), which can carpet the colon withpolyps.

This is one of the strongest predisposing factors in a cancer thatafflicts 5 percent of the U.S. population. Like Mary-Claire King,who told the conference that it might be possible to reverse thealtered phenotype for breast cancer "if we could identify theprotein," Kinzler suggested that diagnosis and prevention ofcolon cancer might also be possible, in this case throughdetection of early changes in the APC gene.

Francis Collins, who last week agreed to head the HumanGenome Project at the National Institutes of Health, discussedthe molecular genetics of neurofibromatosis, a diseasecharacterized by brown spots, bone problems, learningdisabilities and malignancies. The condition is as common ascystic fibrosis (a gene that Collins mapped), with a frequency ofone in 2,500 in all races and a high -- 50 percent -- rate ofspontaneous mutation, Collins said.

Using linkage analysis, Collins mapped the responsible gene,NF1, to chromosome 17, near the centromere.

Comparing the sequence from known genes in other organismsshowed homology with certain proteins that interact with theras oncogene in yeast.

Part of the importance of characterizing the genes involved incancer is to generate new hypotheses about associationsbetween environmental agents and mutational spectra thatcould be tested in the laboratory, concluded Curtis Harris,executive editor of Carcinogenesis.

Finally, Mark Hughes of the Institute of Molecular Genetics atBaylor College of Medicine described a new technique fordiagnosing genetic disorders prior to implementation.

For couples who have already had a child with a lethal orseverely debilitating genetic disease, facing another pregnancycan be filled with anxiety and conflicting emotions. "To start apregnancy with the idea that they might have to stop it, theyare saying they don't want another child like Johnny, who theylove," Hughes explained.

Women in the in vitro fertilization program are superovulatedto make 10 to 20 eggs instead of just one. The man fertilizesthe eggs with his sperm, and the eggs are cultured to the 8 cellstage. One cell from each surviving egg is removed andgenetically analyzed. Healthy embryos, which are homozygousfor the intact gene or heterozygous recessives are implanted inthe uterus.

The method has been reliable in tests of more than 3,000 eggs,and several couples have given birth to healthy babies with themethod.

-- David C. Holzman Washington Editor

(c) 1997 American Health Consultants. All rights reserved.

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