• Research

    Our lab is driven to answer important outstanding questions in human genetics using a diverse set of methods. There has been an historical emphasis on computational analysis, especially population genetic and epidemiological ones, and much of our research requires novel statistical methodology. We have wet lab space and are planning a number of experiments using next generation sequencing, mass spectrometry and other data-dense techniques.

     

    Our research is currently organized around several major themes.

    1. Variation in human chromosome structure.  We have played a leading role in mapping and characterizing the functional impact of structural variants (“SVs”: deletions, duplications, inversions, and more complex rearrangements) over the past 7 years. As the map of common SVs is growing more and more complete, we are now moving towards functional analysis of SV as a class (ie by describing their impact on global gene expression) as well as testing hypotheses regarding individual SVs that show striking evidence for being subject to adaptive evolution.
    2. The causes of new mutation, and variation in mutation rate, both within and among individuals.  Our work on mapping breakpoints of CNVs and rare aneuploidies has provided new insights to the formation of chromosome rearrangements. Most recently, we have developed novel statistical methods for identifying de novo point mutations from next-generation sequencing data, and used this to estimate germ line mutation rates from parent-offspring trios as part of the 1000 genomes project. We would like to continue developing these tools to handle more complex forms of mutation and arbitrary pedigree structure.
    3. Human reproduction. Reproduction is a natural biological system to approach from a genetics background – many open questions pertaining to the origins of mutation and the distribution of mutation frequencies will require an investigation of gametogenesis, fertilization, and pregnancy.  The lab has a number of projects ongoing in this area covering topics such as the biology of spermatogenesis and the placenta. We are trying to facilitate genetic medicine through this work and are eager to collaborate with clinicians in this area.