Dr. Holloway’s main research interests lie in the control of mammalian meiotic progression and the mechanisms governing timing and placement of meiotic recombination events in the germ line.
Dr. Holloway attained her Ph.D from the University of Leicester in the UK, studying the patterns of linkage disequilibrium (LD) in the human genome and directly measuring the frequency and distribution of meiotic recombination events in the male germ line. It is a general feature of most eukaryotic genomes that recombination events are clustered into narrow 2kb intervals, known as hotspots, which tend to punctuate extended blocks of limited haplotype diversity, or coldspots. To date, several human meiotic recombination hotspots have been characterized at high resolution by these single molecule techniques mapping recombination events in single sperm. She identified and characterized hotspots within the human genome, both in terms of crossover frequency, and in terms of non-crossover, or gene conversion, frequency. The main focus of Dr. Holloway’s studies centered around the recombination hotspot within the β-globin gene. In addition to the crossover analysis, she also identified novel deletion breakpoints within the β-globin gene region, which appeared to avoid the hotspot region, proving that this hotspot had little, or no, affect on creating de novo disease causing deletions.
More recently, Dr. Holloway has become interested in the mechanisms controlling crossover placement and frequency within the murine genome. She characterized a mutation in the Mus81 gene in the mouse germ line, and how it affects recombination, seemingly increasing the number of MLH1 foci, the markers for class I crossovers, without increasing the physical number of crossovers, or chiasmata, within the cell. Stemming from this research, she went on to study the Blm mutation in the mouse, which has the adverse effect on recombination, causing many more physical chiasmata in the cell. Taken together, these studies marked the first evidence that these two classes of crossover exist in the mouse, as they had been previously shown to do in yeast and plants. Dr. Holloway has also begun to work on characterizing the effects of multiple mutations within the Fanconi Anemia family of genes, most specifically in a gene called Slx4 (also known as Btbd12, or more recently named FancP), which shows a mild meiotic phenotype coupled with a much more serious pre-meiotic phenotype in the germ line stem cell population. Coupled together, these defects lead to a massive decrease in fertility in these mice. Stemming from this, her research has lead to study other Fanconi Anemia genes within the context of germ line stem cell production and meiotic progression.
The First Annual CRG Retreat in Reproductive and Developmental Genomics was held at Cornell Ithaca on June 14th and 15th. Sponsored by the editorial board of Molecular Reproduction and Development (MRD), and by Wiley Press, this event attracted researchers from all over the NorthEast. For more details, see the website. A meeting review will be published in MRD by trainees in our Center.