Pilot HGDP: Banking, Sequencing, and Haplotyping of ArchivalHuman DNA Samples

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There is widespread interest in having available a representative understanding of the amount and geographical distribution of human biological variation. One way to obtain such information is to collect samples from human populations around the world. In addition, many laboratories in nations around the world already house collections that were made in the past. These 'archival' collections could be an important resource for the future study of human variation, and some of the data could not be collected again, because the populations no longer exist, or the material was from burials, or because of cost. However, archival material is often limited in amount or preservation quality and many questions we would like to ask of genetic data today cannot be asked without large amounts of DNA (genetic material). Fresh samples can be manipulated in the laboratory so that the cells can be grown continually, producing an open-ended supply of DNA, but this cannot be done from dead cells or material in poor preservation. We are working on methods for obtaining large amounts of DNA from such material by making copies of the DNA in an enzymatic (non-living) manner. When this is done, archival materials could be as available as other types of material. We will amplify, in this way, a substantial number of DNA samples from Amazonian and Central American populations that are of widespread interest and anthropological importance. These would be made available to the HGDP DNA bank when that is formally established, so that the samples would be widely available to scientists studying human variation and population history. The methods could also be applied to fresh samples that were very small in quantity (cells from cheek swabs, for example). Archival samples may, however, be degraded in such a way that obtaining long DNA sequences from haplotypes (single chromosomes) could be difficult to obtain. We will work on methods for obtaining such longer sequences, using a gene related to lipid (fat) metabolism, called Lipoprotein Lipase (LPL), as a case in point, because we have extensive data on variation in this gene from other studies. Mutant forms of the LPL gene may be related to human health (heart disease). This work will demonstrate or develop methods for obtaining such long sequences, but will in itself also provide a picture of the global variation in this gene, adding Amerindian variation to that already being documented for other populations.