Human genome diversity initiative.

Abstract

The international Human Genome Project (HGP) is an effort to map and then sequence the human genome, that is, to determine the DNA sequence of all 3 billion nucleotide base pairs in the human DNA complement. This effort involves many agencies and countries and aims to identify, locate on their respective chromosomes, and sequence all functional genes, regulatory regions, and other DNA segments. Foremost among the many anticipated benefits of the project is that the data generated will lead to a better understanding of the function and expression of human genes. Unfortunately, this huge undertaking does not include any systematic consideration of variation in sequence; that is, the HGP does not address that aspect of the genome that is of driving interest in anthropology: human variation. It is the variation of the DNA sequence among individuals, both within and between populations, that illuminates the unique history of each population. That historical record cannot be inferred from a standardized genome sequence or from a gene map derived from a composite individual. In this forum we review some of the uses of studies of variation and then describe the general structure of a new initiative to organize an international project to address DNA variation in the human species. The genome is not a simple homogeneous entity; it is composed of different elements, each able to yield information on aspects of our history and evolution. Molecular genetic tools allow us to learn about the different elements and hence about our past. Although all regions of the genome are composed of nucleotides, the functional content of these sequences varies. Each component reflects particular aspects of human evolution, each has a unique evolutionary tempo, and each affects and has been affected by our evolutionary history in ways different from the others. Detailed analyses of variation in all the components of the human genome will provide essential information to advance many fields of study, including functional studies, forensics, microe volution, and medical applications.