The Trask group studies large-scale facets of genome organization. Our work relies on fluorescence in situ hybridization (FISH), a means of fluorescently tagging specific DNA sequences in chromosomes or nuclei, flow cytometry, a technology for isolating specific chromosomes based on their DNA content, and various tools for genome sequence analysis.

Work in the lab is in four main areas:

1. Molecular cytogenetics

The lab has a long-standing interest in the development and application of FISH and flow cytometry to address questions of genomic structure, such as gene mapping and characterization of gene duplications, and for the detection of chromosome abnormalities in human disease. For example, the now widespread use of multicolor interphase FISH mapping is an outgrowth of research in our laboratory. We continue to be interested in collaborative projects where our experience in FISH and flow cytometry can contribute to a better understanding of human biology and disease.

2. Large scale (polymorphic) gene duplications

Much of the work in our lab focuses on the structure, function, and evolution of regions of the genome that are made complex by their involvement in relatively recent duplications. Some of these duplications have given rise to gene families, such as the olfactory receptor gene family; some are so recent that the number of copies varies among humans; and some might mediate homologous recombination events that can cause human disease.

Olfactory receptor genomics
We are studying the large and complex duplications encompassing members of the olfactory receptor gene family. Members of this 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 studying the genomic organization and function of these genes in mouse and man. We have compiled a web-searchable database of mouse OR genes and their human orthologues.

Subtelomere genomics
The subtelomeric regions of human chromosomes are particularly complex and variable mosaics of multichromosomal duplications. Because subtelomeres contain genes, the compositional variability of subtelomeric DNA may have phenotypic consequences. We are using a combination of molecular and cytogenetic techniques to unravel the structure and function of these highly dynamic regions of the genome.

3. Nuclear Organization

Another aspect of genome organization under study is 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, 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.

4. BAC clones for cytogenetic analyses of the human genome

The Trask lab, as part of the BAC Resource Consortium, has been working on a project to connect the cytogenetic and sequence maps of the human genome. This integration has been accomplished by FISH mapping Bacterial Artificial Chromosome (BAC) clones that contain one or more unique sequence tags. The sequence tags allow each BAC to be positioned on the emerging draft sequence of the human genome. More than 4000 clones have been mapped to date in the Trask lab and over 4000 in other labs, resulting in at least one clone on average per megabase (Mb) for 23 of the 24 human chromosomes. The addition of these landmarks to the draft genome sequence will aid in the detection and molecular characterization of chromosome abnormalities that cause human disease. This resource of BAC clones will be useful in conventional FISH and whole genome CGH arrays to assay for gross karyotypic changes associated with disease. These precisely mapped reagents should also be useful in studies of the organization of DNA in metaphase and interphase chromosomes.

For a list of our recent publications please go to Barbara Trask's Community of Science profile page.

Contact information

Barbara J Trask, PhD
Human Biology Division
Fred Hutchinson Cancer Research Center
1100 Fairview Ave N, C3-168
PO Box 19024
Seattle WA 98109-1024

Tel: (206) 667-1470
Fax: (206) 667-4023