Introduction

The long-term goal of the McCombie lab is to understand genetic variation and its implications on the biology of organisms. Much of this effort is focused on understanding the genetic variation that contributes to severe psychiatric disorders such as bipolar disorder, major recurrent depression and schizophrenia. We are taking several approaches to achieve this goal. In collaboration with Douglas Blackwood and David Porteous and colleagues at the University of Edinburgh we are carrying out large case-control studies to look at genomic variation in candidate genes for major psychiatric disorders. Also in collaboration with Edinburgh group we are carrying out whole genome analysis of families that are highly burdened with major psychiatric disorders particularly bipolar disease and major recurrent depression. In collaboration Jimmy Potash and colleagues at Johns Hopkins University we are carrying out large case-control studies focusing on the variation in genes that make the proteins that function in the synapses of the brain. This study is being carried out on patients with bipolar disorder and we are seeking to see which genes differ when the patient's are compared to the unaffected controls. We also have several other studies underway using both case control methodologies and more recently family-based studies to look at either exon coding regions of the genome or the entire genome to discover variation that contributes to these significant disorders.

In the cancer research area we have several active programs in looking at the changes occurring in the genome during the development and progression of cancer. These studies range from whole genome analysis to focusing on target genes in circulating tumor cells. Much of our effort is focused on the bio informatics needed to understand the variation we detect in these different populations.

We also have an active program in plant genomics. Here we are focused on using new strategies and technologies to carry out de novo sequencing of plant genomes. These studies will ultimately 1provide critical information to breeders attempting to improve important agricultural crops for either food or energy use.