CROSS SPECIES MICROARRAY-BASED GENOMIC SELECTION APPLICATION

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 技术的进步和比较基因组学的价值已经得到证实，导致脊椎动物基因组的多样化样本的测序。即便如此，所有物种中只有一小部分被选中进行基因组测序。这个R21建议的重点是测试和展示一种新开发的基因组技术，基于微阵列的基因组选择（MGS）的能力，作为一种方法，使用现有的非人灵长类动物基因组资源作为跳板，在更大的物种多样性的群体为基础的基因组测序。 迄今为止，我们已经开发了一个MGS阵列的基础上，人类基因组的序列，并测试了该阵列的能力，以捕获orthopathic片段从4个非人灵长类动物（黑猩猩，猩猩，恒河猴和绒猴）在不断增加的进化距离人类（1-10%）。与预期的一样，MGS的效率与与人的分歧呈负相关。也就是说，虽然MGS效率在人类与黑猩猩和猩猩之间基本相等（与人类相同97-99%），但MGS效率在恒河猴中低2.4倍（与人类相同94%），在绒猴中低8倍（与人类相同90%）。总之，我们迄今为止的结果表明，当探针和靶序列具有97.5%的同一性时，MGS方法对探针和靶序列之间的错配具有相当大的容忍度，但随着分歧的增加，该方法的效率显著下降。此外，这些初步结果表明，我们正在量化这种方法的跨物种效率。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Technological advances and the proven value of comparative genomics have led to the sequencing of a diverse sample of vertebrate genomes. Even so, only a tiny fraction of all species have been selected for genome sequencing. The focus of this R21 proposal is to test and to demonstrate the capability of a newly developed genomic technology, microarray-based genomic selection (MGS), as a method that uses the available nonhuman primate genomic resources as a springboard for population-based genomic sequencing in a greater diversity of species. To date we have developed an MGS array based on the sequence of the human genome and have tested the ability of this array to capture orthologous fragments from 4 nonhuman primates (chimpanzee, orangutan, rhesus macaque and marmoset) at increasing evolutionary distances to human (1-10%). As expected the efficiency of MGS was correlated was negatively correlated with the divergence from human. That is, while the MGS efficiency was basically equivalent between human and chimpanzee and orangutan (which are 97-99% identical to human), the efficiency of MGS was 2.4-fold lower in rhesus (94% identical to human), and 8-fold lower in the marmoset (90% identical to human). In summary, our results to date suggest that the MGS methodology is quite tolerant of mismatches between the probe and target sequence when they are 97.5% identical, but the efficiency of this method drops off significantly as the divergence increases. Moreover, these initial results demonstrate that we are well on our way to quantifying the cross-species efficiency of this method.