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

人们普遍希望能够对人类生物变异的数量和地理分布有代表性的了解。获取此类信息的一种方法是从世界各地的人口中收集样本。此外，世界各国的许多实验室已经收藏了过去制作的藏品。这些“档案”收藏可能是未来人类变异研究的重要资源，其中一些数据无法再次收集，因为种群不再存在，或者材料来自埋葬，或者因为成本。然而，档案材料往往在数量或保存质量上受到限制，而且我们今天想要问的许多关于基因数据的问题，如果没有大量的DNA(遗传物质)是无法提出的。新鲜的样本可以在实验室里处理，这样细胞就可以持续生长，产生无限制的DNA供应，但这不能从死亡的细胞或保存不佳的材料中完成。我们正在研究通过以酶(非生物)方式复制DNA来从这种材料中获得大量DNA的方法。当这样做的时候，档案材料就可以像其他类型的材料一样可用了。我们将通过这种方式，从亚马逊和中美洲人口中扩增大量具有广泛兴趣和人类学重要性的DNA样本。当HGDP DNA库正式建立时，这些样本将被提供给HGDP DNA库，这样研究人类变异和人口历史的科学家就可以广泛获得这些样本。这些方法也可以应用于数量非常少的新鲜样本(例如，从脸颊拭子中提取的细胞)。然而，档案样本可能会被降解，以至于很难从单倍型(单染色体)中获得长DNA序列。我们将研究获得更长序列的方法，使用与脂(脂肪)代谢相关的基因，称为脂蛋白脂肪酶(LPL)，作为一个恰当的例子，因为我们从其他研究中获得了关于该基因变异的大量数据。LPL基因的突变形式可能与人类健康(心脏病)有关。这项工作将展示或开发获得如此长序列的方法，但本身也将提供该基因的全球变异图景，将美洲印第安人的变异添加到已经记录的其他种群的变异中。

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.