CROSS SPECIES MICROARRAY-BASED GENOMIC SELECTION APPLICATION

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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.