laboratory is interested in the development and application of advanced genome
technologies, particularly as they apply to our understanding of human disease
and evolution. Areas of special interest include the identification of genetic
factors involved in neurogenetic diseases such as autism, schizophrenia,
microcephaly and macrocephaly, and the use of novel evolutionary genomics
approaches to identify genes and genome structural variations unique to the
human and great ape lineages. Technologies that are used include advanced DNA
sequencing platforms, custom arrayCGH, Bionano optical mapping and novel
bioinformatics tools for the rapid identification of genes and copy number
variations (CNVs) underlying complex human diseases and lineage-specific traits.
These approaches are being tailored to allow the study and copy number
discrimination of highly duplicated genome sequences, such those encoding
Olduvai (DUF1220) protein domains.
domains, human brain evolution and cognitive disease: We were the first to
show sequences encoding Olduvai protein domains had undergone the largest
human-specific copy number increase of any coding region in the genome.
Subsequently, we have generated multiple lines of evidence that link Olduvai
copy number increase to the expansion of the human brain, while also
implicating Olduvai copy number variation in autism and schizophrenia. Based on
such findings we believe that the Olduvai family may constitute a cognitive
genomic tradeoff in our species, capable of playing both a beneficial role (in
brain evolution and cognition) and a detrimental role (in autism and
schizophrenia), and which outcome occurs depends on which, where, how, and when
copies are changing.