Fred Hutchinson Cancer Research Center
1100 Fairview Avenue N, C3-168
P.O. Box 19024
Seattle, WA 98109-1024
University of Washington
Box 358080, C3-168
Seattle, WA 98109
Phone: (206) 667-1470
FAX: (206) 667-4023
The Trask group studies large-scale facets of genome organization. Our work relies on use of molecular cytogenetics and computational genomics. Two techniques, fluorescence in situ hybridization (FISH), a means of fluorescently tagging specific DNA sequences in chromosomes or nuclei, and flow cytometry, a technology for isolating specific chromosomes for molecular analyses based on their DNA content, are used often in our research
The structure, function, and evolution of some of the more complex and variable regions of the human genome are under investigation. One project focuses on the subtelomeric regions of human chromosomes. These regions are a patchwork of sequence-blocks that are duplicated near the ends of multiple chromosomes. They exhibit remarkable polymorphism: the number and location of large blocks can vary among individuals. Because these segments can contain genes, the compositional variability of subtelomeric DNA may have phenotypic consequences. A combination of molecular and cytogenetic techniques is currently being used to unravel the structure and function of these highly dynamic regions of the genome.
We are also studying the large and complex duplications encompassing members of the olfactory receptor gene family. Members of this large gene family are distributed over 40 sites in the human genome, yet each sensory neuron expresses only one gene. In order to determine how the expressed repertoire of olfactory receptors has evolved and is regulated, we are analyzing the genomic organization and function of these genes in mouse and man.
We also study the arrangement of DNA within the interphase nucleus. Two meters of DNA are packed within each nucleus in interphase, the stage when transcription, repair, and replication occur. FISH is used to mark sites of sequences lying at known distances from each other on the same chromosome (or on different chromosomes). By comparing interphase distances between these points to predictions of various physical models, such as that of a random-walk, and developing techniques for labeling specific DNA sequences in live cells, we hope to learn which arrangements, if any, are dictated by functional constraints and which can be explained by the physical forces acting on these large molecules.
Finally, we are applying new cytogenetic technologies to study the DNA lost and gained as cancer cells develop the capacity to metastasize. This work involves development of CGH arrays and collaboration with several oncology research groups.