Abstract: There have been several publications recently that reported DNA sequence alterations in human tumors. There are gene deletions, amplifications, point mutations, translocations, and other genome changes in these samples compared to normal controls. There is also considerable variation in the number of such changes seen in different cancers. Some of the changes particularly those that are mutations in genes driving cellular proliferation will be useful clinically and could be used to monitor disease. At the present time, however, there are more cost effective ways than whole genome sequencing to derive "clinically actionable information" from the molecular analysis of patients and their tumors when they come into the clinic. The number of clinical options available for patients stratified by molecular diagnostics may actually be limited more by the specific treatments available rather than by the ability to stratify the patients in the first place. ... Read more

Abstract: The past two years have brought great progress in the genetics of systemic lupus erythematosus (SLE) heralded by the publication of genome-wide association studies in humans and the identification of susceptibility genes in mouse models of spontaneous lupus. This influx of new information has revealed an ever-increasing interdependence between the mouse and human systems for unraveling the genetic basis of lupus susceptibility. SLE is a complex disease in which defects in several functional pathways have been identified. Genetic variants in a number of genes in these pathways have now been directly associated with lupus in both species. These discoveries have lead to a better understanding of the mechanisms of disease, and offer potential novel target for therapeutic intervention. As a large number of susceptibility genes are identified, lupus genetics will focus on mechanistic and molecular studies, in which mouse models will continue to serve a pre-eminent role. ... Read more

In May of 1998, Craig Venter unveiled an ambitious and audacious plan to complete the sequencing of the human genome sometime in 2001, four years ahead of the anticipated release of the complete human genome sequence being assembled by the Human Genome Project (HGP). The plan was an absolute bombshell for the publicly funded HGP, an international consortium of high profile scientists formed to undertake this mammoth project. Halfway into their fifteen year timeline, the consortium was beginning to lag behind their original timelines having sequenced only 3% of the genome. Venter’s revelation that he was in the process of ... Read more

“The concern that advances in biotechnology will come at a terrible price - the loss of authentic happiness, the loss of what makes life meaningful - struggle, suffering frailty, finitude, and death do not seem to square with what we have already experienced in the wake of biomedical progress. Do those who use glasses, insulin injections, wheelchairs, inhalers, oxygen tanks, hearing aids, or prosthetic limbs feel inauthentic or overcome by a loss of meaning in their lives?”

Arthur Caplan, Ph.D., Director, Center for Bioethics, University of Pennsylvania, Philadelphia, USA. In “Is biomedical research too dangerous to pursue?” Science February 20, 2004.

“High-fat, ... Read more

Drs. Kari Stefansson and Jeffrey Gulcher co-founded deCODE Genetics, Inc. in August 1996 in Reykjavik, Iceland. Dr. Stefansson serves as Chairman, President and CEO and Dr. Gulcher serves as the Vice President for Research and Development and Chief Scientific Officer. Under the company motto “Decoding the Language of Life,” Drs. Stefansson and Gulcher led the team, in collaboration with other groups of scientists around the globe, achieved significant accomplishment in “decoding” the genetic information associated with a number of widely prevalent, common and complex diseases such as heart diseases, diabetes, stroke, arthritis, schizophrenia, Parkinson’s disease etc. The valuable information was ... Read more

Natural antisense transcripts are endogenous transcripts that contain sequences that are complementary to other transcripts. Such complementary transcripts may be transcribed from opposing DNA strands at the same genomic locus (cis), or from different loci (trans), for example, pseudogenes. Notably, both types of antisense RNAs are genome-encoded and transcribed by DNA-directed RNA polymerases. A third putative source of antisense RNAs is transcription of the sense mRNA by an RNA-dependent RNA polymerase (Volloch et al., 1996).

Although only a few examples have been studied in detail (reviewed in Kumar and Carmichael, 1998; Lavorgna et al., 2004), a significant number of naturally occurring ... Read more

The Human Genome Project has produced a map detailing a vast genetic frontier that will continue to provide useful insights for the treatment of human diseases. The large number of uncharacterized genes reflects the degree of our progress and the wealth of opportunity. Functional genomics will broadly impact our understanding of disease and illuminate the path to better therapeutics.

One of the most definitive ways to determine gene function is to specifically inactivate a gene through knockout approaches, thereby permitting comparisons between genetically matched (i.e., isogenic) knockout and wild-type controls. Gene knockout technologies have been performed in a variety of model ... Read more

Given the recent sequencing of the human genome, we have entered into a new era of medicine, “Genome Medicine,” that transcends our traditional notion of pharmacology and drug therapies. We now have the potential to address the genetic root of disease pathology, either by identifying and modifying the function of the gene product responsible for a given pathology through pharmacological means, or by directly modifying the gene with gene therapy. However, as is the case with most new pharmacological treatments, gene therapy has encountered numerous challenges that have limited its efficacy in both preclinical and clinical situations. Some of these ... Read more

In the past few years, many studies have suggested that alternative splicing is a widespread mechanism of functional regulation in the human genome. Cancer-associated splice variants have also been reported for genes such as EGFR, CD44, and recently many others (Xu et al., 2003). High throughput genomics data, such as those obtained from EST (expressed sequence tag) sequencing, have provided a major new opportunity for discovering cancer-specific alterations in splicing (Wang et al., 2003). Over 4 million human ESTs have been sequenced, and most can be classified both by their tissue of origin and whether they were derived from a ... Read more

Pseudogenes are dysfunctional genes, i.e., they do not encode for proteins. Recent studies indicated that they are nearly as abundant as functional genes (30,000). The existence of the massive amount of these “molecular fossil” in the human genome, remains a mystery. 

Hirotsune and colleagues of Saitama Medical School, Japan have found that one such pseudogene is not junk, but in fact is down right precious — mice would die when the pseudogene was disrupted (Nature 423:91-96, May 1, 2003). Among the many mouse lines that were produced, while studying a fruitfly gene Sex-lethal by its random insertion into the mouse genome, ... Read more