Thursday, November 1, 2007
PHILADELPHIA - A multi-center, National Institutes of Health-funded report that appears in the scientific journal Genome Research details the first assembly, annotation and comparative analysis of the domestic cat genome, Felis catus. A University of Pennsylvania researcher is on the team.
The DNA of a 4-year-old Abyssinian cat named Cinnamon was sequenced using light (two-fold) genome sequence coverage, one of several mammals currently under analysis using this technique. Researchers leveraged information from previously sequenced mammalian genomes as well as previous gene-mapping studies in the cat. In doing so, they found that Cinnamons sequences spanned about 65 percent of the gene-containing regions of the feline genome.
To make sense of Cinnamons raw sequence data, a multi-center collaboration of scientists was assembled that included Urs Giger, section chief of Medical Genetics at Penns School of Veterinary Medicine.
The feline genome sequence tremendously improves the research of many feline characteristics and diseases, said Giger, who has worked more than two decades on several hereditary disorders in cats, and it is hoped that this project will improve the treatment and prevention of the approximately 200 hereditary diseases in cats. Each defect also represents homologues of human disease, and thus the advances made in cats can also benefit mankind.
The similarity between the cat genome and six recently completed mammalian genomes (human, chimpanzee, mouse, rat, dog and cow) allowed scientists to identify 20,285 putative genes in the cat genome. The comparison also revealed hundreds of chromosomal rearrangements that have occurred among the different lineages of mammals since they diverged from a diminutive ancestor that roamed the earth among the dinosaurs some 100 million years ago.
The genome sequence analysis is expected to lead to health benefits for domestic cats, 90 million of which are owned by Americans, according to The Humane Society. Additionally, the domestic cat serves as an excellent model for human disease, one reason why the National Human Genome Research Institute initially authorized the cat genome sequencing project three years ago.
Domestic cats possess more than 250 naturally occurring hereditary disorders, many of which are similar to genetic pathologies in human beings.
For example, Cinnamons pedigree carries a genetic mutation that causes retinitis pigmentosa, a degenerative eye disease that can lead to blindness. Retinitis pigmentosa affects 1 in 3,500 Americans.
The domestic cat also serves as an excellent model for human infectious diseases, including HIV/AIDS. Feline immunodeficiency virus is a genetic relative of human immunodeficiency virus.
Using the cat genome sequence data, researchers identified several hundred thousand genomic variants which can be used to determine the genetic basis for common hereditary diseases. Scientists have already used these variants to identify the causative gene for Cinnamons retinitis pigmentosa, with the results originally published in the May/June 2007 issue of the Journal of Heredity. These variants will also be useful for parentage testing, forensic analysis and studies of evolution, including the reconstruction of domestication processes, fancy-breed development and ecological adaptation among the great roaring cats.
Researchers also analyzed the feline genome for interesting features such as microRNAs, nuclear genomic fragments and a vast sea of selfish DNA-like repetitive elements. The repetitive elements included scores of genomic stretches from historic retroviruses, some with known links to cancer.
The Cat Genome Project is based at the National Cancer Institute. The sequencing data were generated by Agencourt Bioscience Corporation. Funding for the project was supported in part by the Intramural Research Program of NIH, the National Cancer Institute, the Center for Cancer Research and in part with federal funds from the National Cancer Institute and the NIH.