Obesity is becoming the major epidemic of the 21st century, and we are studying this disease in an integrated way - from the perspective of genomics, microbiomics, and epigenomics. We are following a large group of newborn children until they are at least 3 years of age.
With sequencing now possible at high depth, we aim to examine mutation process directly, by examining the DNA of children and their parents. Mitochondrial DNA (mtDNA) provides a good starting point for such an investigation due to its compact size and high mutation rate.
Approximately 13% of the genome can fold into DNA structures different from the B-form double-helix discovered by Watson and Crick. Such “non-B DNA” structures include cruciforms, triplexes, slipped-strand structures, G-quadruplexes (G4s), Z-DNA, and bent DNA. They form at certain DNA sequence motifs that are ubiquitous in the genomes of prokaryotes and eukaryotes.
Mutation rates vary at a fine scale - even within individual chromosomes. We are using statistical modeling to study such regional variation in mutation rates. Moreover, we are able to segment the genome into regions with high and low rates of different mutation types.
We are determining the gene repertoire and structure of the Y chromosome in several mammalian species. The Y chromosome has very high rates of mutation compared with other chromosomes in the mammalian genome due to a higher number of cell divisions in the male than female germ line.
