Centromere Structure and Function

Centromeres of mammalian chromosomes are structurally and epigenetically complex. The dominant class of DNA at human centromeres is a family of highly repeated, tandemly arrayed alpha satellite DNA. Both experimental and computational efforts are directed at determining the cytological, molecular and genomic organization of long arrays of alpha satellite, which measure 300-5,000 kb in length, examining the genomic and epigenetic nature of boundaries of the functional centromere in both human and model organisms, and revealing the complex evolutionary history of centromeres. (click for MORE) 

Human Artificial Chromosomes

Understanding the complex centromeres of natural human chromosomes has served as a platform for creation of human artificial chromosomes, first accomplished in our lab in 1997.  Current efforts involve optimization of centromere sequences and development of new vectors to improve the efficiency of human artificial chromosome formation.(click for MORE) 

X Chromosome Inactivation

In female mammals, most genes on one X chromosome are silenced as a result of X-chromosome inactivation.  Previous studies have included determining the profile of X-linked genes that appear to "escape" inactivation, identifying and characterizing the X inactivation center in mouse and humans that appears to be required for inactivation to occur, and examining the cytological, genomic and chromatin patterns of epigenetic modification along the inactive X chromosome.  Mechanisms of inactivation, chromosome choice and factors responsible for the escape ability of some X genes are all issues being addressed in the Willard Lab.  A variety of approaches include in vitro studies, use of mouse models, computational analyses, and epigenetic studies. (click for MORE) 

Lemur Biology and Primate Genome Evolution

Lemurs hold a key position at the base of the primate evolutionary tree and include more than 50 species. Our interests center on the biology of different lemur species and how we can use a deep understanding of genetic and genomic diversity among and within different lemur species to add to our understanding of primate genome evolution. The Duke Lemur Center (DLC) houses over 15 species of lemurs as well as numerous subspecies. We are using small-scale sequencing to obtain orthologous nuclear sequence from each lemur species at DLC for genomic and phylogenetic comparisons. We hope these primer pairs and sequences will constitute a "genetic toolkit" that can be used by all future lemur researchers for multi-species comparisons. (click for MORE)