Human Genome
Researchers have uncovered evidence that major evolutionary changes are more likely to occur in approximately 400 'fragile' genomic regions that account for only 5 percent of the human genome. The findings, reported in the June 24 issue of the Proceedings of the National Academy of Sciences (PNAS), undercut the widely held view among scientists that evolutionary breakpoints ? disruptions in the order of genes on chromosomes ? are purely random. Apart from its implications for evolutionary theory, the study could have major implications for medical research related to diseases such as leukemia, which are caused by clinical (rather than evolutionary) chromosomal breakpoints.
Using a multiple-gene analysis technique, German researchers have gained new insights into specific genetic alterations that lead to congenital heart defects, according to a report in today's rapid access issue of Circulation: Journal of the American Heart Association. The technique, called microarray analysis, allowed investigators to identify specific patterns of gene expression in the entire human genome associated with common types of congenital heart defects. They sought to demonstrate the feasibility of using gene array analysis to study congenital heart defects. But their findings could represent an early step toward developing effective strategies to improve the quality of life in children and adults with heart defects.
Scientists at the National Human Genome Research Institute (NHGRI) and at the National Institute of Neurological Disorders and Stroke (NINDS) have identified the gene responsible for two related, inherited neurological disorders, and have, for the first time, directly implicated this gene and its enzyme product in a human genetic disease.
A team led by the National Human Genome Research Institute today announced the discovery of the genetic basis of a disorder that causes the most dramatic form of premature aging, a finding that promises to shed new light on the rare disease, as well as on normal human aging. In their study, to be released online next week in the journal Nature, researchers identified the genetic mutations responsible for Hutchinson-Gilford progeria syndrome (HGPS), commonly referred to as progeria. Derived from the Greek word for old age, "geras," progeria is estimated to affect one in 8 million newborns worldwide. There currently are no diagnostic tests or treatments for the progressive, fatal disorder.
The International Human Genome Sequencing Consortium, led in the United States by the National Human Genome Research Institute (NHGRI) and the Department of Energy (DOE), today announced the successful completion of the Human Genome Project more than two years ahead of schedule. Also today, NHGRI unveiled its bold new vision for the future of genome research, officially ushering in the era of the genome. The vision will be published in the April 24 issue of the journal Nature, coinciding with the 50th anniversary of Nature's publication of the landmark paper by Nobel Laureates James Watson and Francis Crick that described DNA's double helix. Dr. Watson also was the first leader of the Human Genome Project.
Scientists have used a powerful gene-mapping technique to produce the clearest picture yet of all the genes of an animal ? the microscopic worm Caenorhabditis elegans (better known as C. elegans). Scientists believe the same technique may be used to bring the current, somewhat blurry picture of the human genome into sharper focus. The study, in Nature Genetics, describes an effort to locate and precisely identify all of the approximately 19,000 genes that have been predicted to exist in the genome of C. elegans.
Researchers have completed sequencing the genome of Bacteroides thetaiotaomicron, one of the most prevalent bacteria that live in the human intestine. "Now that the draft sequence of the human genome is complete, it's critical that we study the environmental forces that regulate our gene expression," says principal investigator Jeffrey I. Gordon. "Humans enjoy mutually beneficial relationships with billions of bacteria that live in our gut. Discovering how these microbes manipulate our biology to benefit themselves and us should provide new insights about the foundations of our health and new therapeutic strategies for preventing or treating various diseases."
Most of the time, most of the estimated 35,000 genes in the human genome are silent, securely stored away in the tightly coiled structure of chromatin, which makes up chromosomes. Inside chromatin, the DNA is wound around small proteins called histones, making it unavailable to the cellular machinery that would otherwise read its coded genetic information. Specific cell and tissue types are characterized by the carefully controlled activation of selected sets of signature genes. Now, a team of researchers at The Wistar Institute reports discovery of a family of molecular complexes involved in the repression of extensive sets of tissue-specific genes throughout the body. Additionally, one member of the family involved in repressing brain-specific genes in other types of tissues has been found to include a gene thought to be responsible for X-linked mental retardation when mutated. Other components of these complexes have been associated with certain forms of leukemia.
The technique that helped revolutionize modern biology by making the mouse a crucible of genetic manipulation and a window to human disease has been extended to human embryonic stem (ES) cells. In a study published today (Feb. 10) in the online editions of the journal Nature Biotechnology, a team of scientists from UW-Madison reports that it has developed methods for recombining segments of DNA within stem cells.
Researchers studying rice genomes have identified the species' first active DNA transposons, or "jumping genes." The scientists also discovered the first active "miniature inverted-repeat transposable element," or "MITE," of any organism. Rice (Oryza sativa), an important food crop worldwide, has the smallest genome size of all cereals at 430 million base pairs of DNA. About 40 percent of the rice genome comprises repetitive DNA that does not code for proteins and thus has no obvious function for the plant. Much of this repetitive sequence appears to be transposons similar to MITEs. But like most genomes studied to date, including the human genome, the function of this highly repeated so-called "junk DNA" has been a mystery. The discovery of active transposons in rice provides startling new insights into how genomes change and what role transposons may play in the process.
An international conference of European scholars and scientists, with funding from the government of Flanders, goes on record supporting research leading toward safe and effective human germ line genetic modification, saying that it does not violate human rights, including any "so-called right to be born with a human genome that has not been modified by artificial means."
A California research team has mapped an entire group of human enzymes, providing important information for the development of a new generation of drugs to treat cancer and other diseases. The findings will be published in the Dec. 6 issue of Science. In the study, the team from the Salk Institute for Biological Studies and the biotechnology company SUGEN created a detailed catalog of the 518 protein kinase genes encoded by the human genome. Protein kinases are among the most important regulators of cell behavior. By chemically adding phosphate groups to other proteins, they control the activity of up to 30 percent of all cellular proteins, and are involved in almost all cellular functions.
The international Mouse Genome Sequencing Consortium today announced the publication of a high-quality draft sequence of the mouse genome - the genetic blueprint of a mouse - together with a comparative analysis of the mouse and human genomes describing insights gleaned from the two sequences. The paper appears in the Dec. 5 issue of the journal Nature. The achievement represents a landmark advance for the Human Genome Project. It is the first time that scientists have compared and contrasted the contents of the human genome with that of another mammal. This milestone is all the more significant given that the laboratory mouse is the most important animal model and is widely used in the study of human diseases.
An expert in computational biology at the University of California, San Diego (UCSD) estimates that it took many more evolutionary genome rearrangements than previously thought -- both large and small -- to account for differences in the human and mouse genomes. The findings are included in two landmark papers announced today.
The National Human Genome Research Institute said today it has made several key personnel changes, including the appointment of a new scientific director to run its intramural research program, a new director for the extramural program that oversaw the Human Genome Project and new advisors in the Office of the Director.
