ScienceDaily (Aug. 9, 2010) — In one of the first efforts of its kind, UCLA researchers have taken mammalian genome maps, including human maps, one step further by showing not just the order in which genes fall in the genome but which genes actually interact.
This map of subnetwork centered around the gene cyclooxygenase-1 (COX1 or PTGS1) involved in synthesis of prostaglandins, which control smooth muscle activity in the body along with many other physiological functions. (Credit: UCLA)
The findings, published in the August issue of the journal Genome Research, will help researchers better understand which genes work together and shed light on how they collaborate to help cells thrive or die.
Mammals, including humans, have roughly 20,000 different genes. Genes hold instructions to create proteins that determine not only physical characteristics, like outward appearance, but all bodily processes, from moving blood through the veins to stimulating the immune system to attack a cold virus. They can also be pivotal in the development of diseases like cancer.
Each mammalian cell contains the full complement of genes, although depending on the activity of the cell, not all the genes are active. The genes engage not only in one-on-one interactions but also create wide networks involving dozens of genes. Little had previously been known about which genes work together most often in mammals and the networks they form.
For this study, the UCLA scientists used human radiation hybrid genome maps developed several years ago for the worldwide Human Genome Project, as well as several other mammalian radiation hybrid maps, for dogs, cats and mice.
They found substantial overlap and commonalities between gene interactions and networks across all four species, thus creating the first complete and comprehensive genetic interaction maps for mammalian cells.
Previous research had mapped interactions between proteins, which are set in motion by genes, but not the genes themselves, which provide more direct and nearly comprehensive information about the connection strength between genes. Researchers say this is an important step in furthering the understanding of the role each gene plays in triggering a process or function in the body.
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A genome-wide map of human genetic interactions inferred from radiation hybrid genotypes
Andy Lin1, Richard T. Wang1, Sangtae Ahn2, Christopher C. Park1 and Desmond J. Smith1,3
-Author Affiliations
1 Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, California 90095, USA;
2 Signal and Image Processing Institute, University of Southern California, Los Angeles, California 90089, USA
Abstract
Using radiation hybrid genotyping data, 99% of all possible gene pairs across the mammalian genome were tested for interactions based on co-retention frequencies higher (attraction) or lower (repulsion) than chance. Gene interaction networks constructed from six independent data sets overlapped strongly. Combining the data sets resulted in a network of more than seven million interactions, almost all attractive. This network overlapped with protein–protein interaction networks on multiple measures and also confirmed the relationship between essentiality and centrality. In contrast to other biological networks, the radiation hybrid network did not show a scale-free distribution of connectivity but was Gaussian-like, suggesting a closer approach to saturation. The radiation hybrid (RH) network constitutes a platform for understanding the systems biology of the mammalian cell.
Footnotes
↵3 Corresponding author.
E-mail DSmith@mednet.ucla.edu; fax (310) 825-6267.
[Supplemental material is available online at http://www.genome.org.]
Article published online before print. Article and publication date are at
Copyright © 2010 by Cold Spring Harbor Laboratory Press
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