Comparative Microarray Sequencing of Chimpanzee genomes

描述(申请人提供)：随着人类基因组序列的完成，对黑猩猩基因组进行测序是有根本原因的。首先，黑猩猩为人类疾病的生物医学研究提供了一个很好的动物模型。识别导致基因表达差异的固定序列变异可能会解释对艾滋病毒、癌症和阿尔茨海默病等共同疾病的不同生理反应。人类和黑猩猩之间98-99%的DNA序列相似性和蛋白质的近似性表明，物种特有的基因调控可能解释了它们的生物学差异，如颅骨形态和认知。此外，对人类和黑猩猩的多态比率和基因组中固定的差异进行比较，将指出选择性压力可能在维持基因组完整性方面发挥作用的区域。这些区域是进一步研究它们的生物学作用的候选区域。最后，与其他非人类灵长类动物的比较将表明，起源的谱系存在固定的差异，准确地指出了区分人类和黑猩猩的区域。对于这些比较序列研究，需要了解在黑猩猩种群中发现的种内遗传变异。PerLegen的微阵列技术可以快速、经济和准确地确定人类和黑猩猩基因组之间高度保守区域的位置和序列差异。

DESCRIPTION (provided by applicant): With the finishing of the human genome sequence, there are fundamental reasons to sequence the chimpanzee genome. First, the chimpanzee provides an excellent animal model for biomedical research of human diseases. Identifying fixed sequence variants responsible for differential gene expression may explain the different physiological responses to shared diseases such as HIV, cancer and Alzheimer's disease. The 98-99% DNA sequence similarity and the near identity of proteins between human and chimpanzee suggest species-specific gene regulations likely account for their biological distinctiveness such as cranial morphology and cognition. Additionally, comparison of human and chimpanzee polymorphism rates and fixed differences across the genome will indicate regions in which selective pressure may play a role in maintaining genomic integrity. Such regions are candidates for further investigation of their biological roles. Finally, comparisons to other non-human primates would indicate the lineage of origin in fixed differences, pinpointing regions involved in distinguishing humans from chimpanzees. For these comparative sequence studies, an understanding of the intraspecific genetic variation found within chimpanzee populations is required. Perlegen's microarray technology allows rapid, economical, and accurate determination of where and what sequence differences exist in highly conserved regions between human and chimpanzee genomes.