American Association of Clinical Endocrinologists Meeting, May 2002

Sequencing the human genome

J. Craig Venter (Rockville, Maryland) gave the keynote address, discussing his work in the sequencing of the human genome using high through-put technologies with biocomputational analysis. He reviewed his initial work in the field during the 1980s sequencing the epinephrine receptor, a task which took a decade. He subsequently developed an approach using a “shotgun sequencing strategy” using mechanical shearing to cut a whole genome into different sized expressed sequence tags (ESTs), developing a computational algorithm to piece the EST into a full genome. With the development of more powerful algorithms and computers, his group progressed from sequencing the Haemophilus influenzae genome, 1.8 Mbp, in 1995, to analyzing the Drosophila genome, 120 Mbp, and to sequencing the 3,000-Mbp human genome, reported in June 2000. “The biggest surprise,” Venter stated, “was the small number of genes.” Approximately 26,000 different genes were present, with some sections of chromosomes highly dense in genes, but many sections with very few genes. Overall, only 1.1% of the genome actually encodes genes, and 42% of those discovered are of unknown function. Comparison of the genomes of Drosophila with man reveals that new genes appear in the immune and hemostatic systems as well as many aspects of cell signaling, particularly those transcription factors that regulate the expression of other genes.

Venter noted the phenomenon of repeat gene sequences in the human genome. Chromosome 19 has the highest density of genes, many of which are repeated in other chromosomes. Analysis of these repeats, he suggested, may allow assessment of our “genetic history.” The mouse genome is 90% the size of that of …