| Author: Aaron Hall |
Scientists analyzing the sequence of the longest (685-kb) continuous segment of human DNA published to date have uncovered powerful information about the human immune system that may help doctors prevent autoimmune diseases such as arthritis and multiple sclerosis. Analysis of the human beta T-cell receptor (TCR) locus comprising a complex family of genes was reported in the June 21, 1996, issue of Science (272, 1755-62). The locus contains a cluster of genes that play a vital role in recognizing foreign viruses, bacteria, and cancer cells and in triggering the body's defense mechanisms to destroy these invaders.
Authors Lee Rowen and Leroy Hood (both at University of Washington, Seattle) and Ben F. Koop (University of Victoria, Canada) reported identifying and classifying all related genes at the locus. This information will enable development of tests specific to each individual gene, allowing easier identification of genes involved in autoimmune diseases. "This may ultimately lead to a new form of medicine focusing on preventing, not curing, diseases," said Hood. The research was funded by a grant from DOE with support from NIH.
Unexpected findings include identification of genes encoding trypsinogen, an important enzyme for digesting protein-rich food. The discovery raises the possibility that trypsinogens and immune receptors may work in concert. Researchers also confirmed that a piece of the immune receptor gene has been copied and moved from chromosome 7 to chromosome 9, providing evidence of evolutionary transfer of genes. The Science cover depicts chromosomes 7 and 9 with the TCR and trypsinogen genes identified.
The authors attribute their dual achievements sequencing and analyzing the entire TCR locus to advances in automated DNA sequencing and development of computational tools for sequence assembly and analysis.
Importance of Computational Tools
According to Rowen, "Computational tools are critical they are used to store and manage large amounts of data and conduct sequence comparisons. They are also essential for detecting and organizing large-scale patterns within long stretches of sequence."
Sequences can be analyzed in a number of ways, she said. For example, two sequences covering the same chromosomal region in different people can be compared for variations, some of which may correlate with disease susceptibilities. A sequence also can be compared against other sequences in large public databases, for example, gene-coding sequences (cDNAs or ESTs) against genomic sequences, sequences from one species against those in another species, or amino acid sequences against protein motif databases.
The laboratory at the University of Washington is one of six centers chosen recently by NIH to participate in a pilot study of large-scale human sequencing in the Human Genome Project [HGN 7(6), 20]. It is also taking part in the DOE pilot study of BAC end sequencing |
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