This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5).
The mouse t complex is a naturally occurring chromosomal variant consisting of four segments that are inverted relative to the normal homolog. Genetic recombination between the two chromosome types is rare, making it difficult to analyze the biological roles of individual mutant genes within the t complex. This project aims to develop and characterize segmental recombinants as a gene mapping resource for the mouse t complex, and to investigate a naturally occurring segmental recombinant as a possible evolutionary precursor to the t complex. This research focuses on the fourth inversion of the t complex. This inversion harbors the greatest number of genes affecting t complex phenotypes (sperm function and embryonic development), and has persisted in mouse populations for an estimated 1.5 million years. Aim 1 is designed to generate recombinant chromosomes using a genetic cross that has proven to yield segmental recombinants. As a result of this aim, a panel of recombinant chromosomes will be created for gene mapping purposes. Aim 2 is designed to assess the properties conferred by the recombinant chromosomes. Genetic crosses will be used to determine the presence or absence of these properties for each recombinant chromosome. This will allow particular candidate genes to be excluded or included as factors contributing to these biological properties. Aim 3 will characterize a unique variant of the fourth inversion using DNA sequencing, genetic recombination assessment, and gene expression studies. This unique variant may represent a "molecular fossil" present at the time when the inversion arose in the ancestral mouse population. There are two important outcomes from this work. First, these experiments will generate a mapping resource that will be used to identify the genes responsible for fundamentally important mammalian biological processes. Second, this work is designed to elucidate the origin and evolution of the largest inversion in the mouse t complex, contributing substantially to the long-standing debate about the reasons why the t complex exists in nature at a frequency lower than expected.
Chicago State University (CSU) serves a largely underrepresented clientele, with a student enrollment of >83% African Americans and a location in one of the largest African American communities in the US. The primary mission of CSU is teaching. In the science disciplines at CSU, research and research training are recognized as being essential to the teaching and intellectual advancement of the clientele. The activities described in this project will take place in a laboratory environment in which training of both undergraduate and MS-level graduate students has been a priority for 18 years. The project principal investigator currently coordinates two research training programs designed to increase the number of underrepresented minorities entering Ph.D. programs in the science disciplines: A summer research training program for CSU undergraduate science majors, and a MS to Ph.D. Bridge program for CSU Biology graduate students. Students in both of these programs will participate in hypothesis-driven research described in this project. In addition, because CSU is the lead institution of the NSF-funded Illinois LS-AMP consortium, LS-AMP scholars will have an opportunity to contribute to this research. The principal investigator also will incorporate experiments from this work into a CSU lab course (Recombinant DNA Laboratory) as a means to teach modules on DNA isolation, gene expression, and bioinformatics. Taken together, these approaches will (1) recruit more underrepresented minorities to research activities, (2) afford MS students in the lab an opportunity to mentor undergraduates through organized research training activities, and (3) increase the number of underrepresented minorities going to Ph.D. programs.
