The Use of DNA Microarrays to Study Non-Human Primate Genetics

Joseph Hacia
University of Southern California
Keck School of Medicine

The Human Genome Project has already had a major impact on a wide variety of scientific disciplines ranging from biomedical research to evolutionary biology. A complete database of human genetic information is an invaluable resource for researchers interested in defining the biochemical basis for distinctly human traits. However, it is only a piece of the puzzle, as similar genetic information from non-human primates is needed to make meaningful comparisons.
DNA microarrays have emerged as a powerful new technology for rapidly acquiring genetic information from virtually any organism. This technology has been used to uncover DNA sequence changes between members of closely related species as well as DNA sequence variation within a species. In addition, it can be used to measure the relative intracellular concentrations of several thousand mRNA species simultaneously. This versatile technology will have a major impact on a number of different fields including human evolutionary biology.
I will present the results of DNA microarray experiments designed to study inter- and intra-species DNA sequence variation in non-human primates. I will focus on two topics: (1) evolutionary sequence analysis of the hereditary breast and ovarian cancer BRCA1 gene in primate lineages and (2) analysis of single nucleotide polymorphisms in humans and great apes. The relative strengths and limitations of the approaches will be discussed.
I will also discuss experiments aimed at measuring differences in gene regulation in human and non-human primates. In collaboration with Dr. Oliver Ryder at the Center for the Reproduction of Endangered Species, I have obtained RNA samples from at least ten separate human, chimpanzee, and gorilla fibroblast cell lines. The relative amounts of over 12,000 distinct mRNA species present in each cell line will be determined. A database of inter- and intra- species gene expression differences will be established. Results from these experiments could shed light on fundamental biochemical differences among human and non-human primates.


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