Genetics update : impact of the human genome projects and identification of a stroke gene.

Abstract

Two articles were published in February 2001 that will have a significant impact on our understanding of human development, the pathogenesis of many human diseases, and the discovery of new therapies for many disorders.1 2 These articles deal with the mapping of the human genome. Two different entities, one a publicly traded company (Celera) and the other the Human Genome Project (HGP, sponsored and funded by NIH), published somewhat different versions of the human genome. The HGP began in 1990 (although extensive sequencing of the human genome began in 1995) and cost approximately $3 billion, while the Celera effort began in 1998.1 2 The HGP involved multiple laboratories in the United States and abroad. The 2 projects produced maps that differ from each other in terms of completeness, order of some genetic markers, and the ability to search the database for specific DNA sequences. A comparison of some features of both projects is in Table 1⇓. The challenge of sequencing the 3 billion base pairs of the human genome required the development of unique tools and approaches. Celera constructed a facility capable of high-throughput sequencing at a rate of 175 000 reads per day and conducted sequencing 24 hours a day, 7 days a week. The HGP divided the sequencing task among several large laboratories with demonstrated expertise in large-scale DNA sequencing. The strategy employed by the HGP focused on subcloning the human genome into bacterial artificial chromosomes (BAC), which were then sequenced and properly arranged.1 Each BAC could hold an insert of 150 000 bases on average. Celera used a shotgun whole genome approach to sequencing, which involved generating many small, random fragments of DNA for sequencing.2 After the sequence was determined, advanced computational algorithms combined with publicly available mapping and sequence information …