Nikale Pettie and Matt Cring Present at Genetics Student Seminar 4/17/17

 

EVALUATING RECOMBINATION REGULATION: LESSONS FROM HYBRIDS OF DROSOPHILA

N Pettie1, J Comeron1,2 , and A Llopart1,2

1 Interdisciplinary Graduate Program in Genetics, University of Iowa, 2 Department of Biology, University of Iowa

Meiotic recombination is a polygenic, highly regulated, evolutionarily conserved process that increases genetic diversity and ensures proper chromosome segregation.  Despite the almost universal presence of recombination among eukaryotes, the molecular processes responsible for the number and distribution of recombination events across genomes are highly variable. The mechanisms responsible for hotspot localization of meiotic recombination, for instance, are not conserved.  Recombination localization in most mammals including humans and mice is regulated by PRDM9, which targets specific sequences of DNA motifs. In canids, however, there is no active PRDM9 and recombination is highly correlated with CpG content, which is also the case in yeast. Recombination in Drosophila appears to be controlled differently than in mammals or yeast.  Recombination rates and distribution in Drosophila are influenced by many epigenetic factors, such as age, nutrition, temperature, and transcription.  Here, we use the term epigenetic to describe any factor that changes the ‘phenotype’ of recombination, including gene expression changes, while maintaining equivalent genetic material. We will generate high-resolution recombination maps from two closely related species of Drosophila, D. yakuba and D. santomea, to study short-term evolutionary differences between species. We will also generate high-resolution recombination maps in their hybrids to evaluate the hypothesis that the independent evolution of this polygenic ‘phenotype’ of recombination in the two lineages has led to incompatible interactions in hybrids and ultimately distorted genetic maps.

 

Genetic therapeutic strategies for the BBS1 M390R mutation

Matthew Cring

Bardet-Biedl syndrome (BBS) is a rare ciliopathy caused by mutations in a number of cilia related genes. Common features of BBS include retinopathy, male infertility, polycystic kidney disease, hypogonadism, polydactyly, obesity, and several others. Currently, there are no efficacious treatments for BBS, illustrating a critical need to develop therapeutic strategies. The most common genetic cause of BBS is the M390R mutation in BBS1, accounting for approximately 20% of all genetically diagnosed BBS cases. BBS1 is normally part of a multi-protein complex called the BBsome, a complex that is important for trafficking proteins to cilia and the cell membrane. Due to the accessibility of the eyes and testes, the retinal degeneration and male infertility phenotypes of BBS are strong candidates for treatment via gene therapy and gene correction. Previous work in mice focused at using gene therapy for the treatment of retinal degeneration in BBS mice has met some challenges, as overexpression of BBS1 causes toxicity and further loss of photoreceptor cells. Our lab has previously shown that postnatal correction of BBsome proteins can halt photoreceptor death and restore male fertility in mouse models of BBS. Continued work is underway using naked DNA, viral vectors, and CRISPR-Cas9 mediated gene correction to ameliorate the phenotypes of BBS in mouse models.

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Posted on April 13, 2017, in Uncategorized. Bookmark the permalink. Leave a comment.

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