Welcome to the fifth edition of Gene Genie, the carnival devoted to genes, clinical genetics and genomics. Gene Genie is the brainchild of Bertalan, whose aim with the carnival is to cover the entire human genome by the year 2082. That’s no mean feat, as the human genome is believed to contain some 30,000 genes. That number was presumably reached using the conventional definition of a gene as a discrete length of DNA that contains the coding sequence of a single protein and resides at a specific location (called a locus) of a chromosome.
For geneticists, who are concerned with the gene as a unit of inheritance, that definition is fine. But for molecular biologists, who study the physical processes by which information in the DNA is used to synthesize proteins, it is inadequate, because in recent years, they have discovered, among other things, that the coding sequences of some genes overlap with those of others, and that parts of the coding sequences for some proteins are separated by large distances or are actually found on different chromosomes. Nevertheless, lets rub those chromosomes, and see what genes the genie has for us in this edition.
First of all, Hsein-Hsein Lei provides details about a DNA test for Type 2 diabetes at Genetics & Health. Type 2 (or non-insulin dependent) diabetes, is a metabolic disorder that affects up to 100 million people worldwide. It occurs later in life, when the body becomes resistant to insulin, the hormone that normally mediates the uptake by cells of glucose from the bloodstream, leading to high blood sugar levels (hyperglycaemia). The gene being tested for illustrates nicely the inadequacy of the conventional definition of the gene – its coding sequence lies entirely within that of a gene encoding the transcription factor 7-like 2 protein. By the way, people with type 1 diabetes need to inject themselves with insulin regularly to maintain their blood sugar levels. The insulin gene was one of the very first genes to be cloned. Researchers from Genentech, the world’s first biotechnology company, generated a recombinant insulin gene that they expressed in bacteria. This eventually enabled the synthesis of insulin on an industrial scale, for the benefit of those suffering from type 1 diabetes.
Another condition for which genetic testing is available is Huntington’s Disease (HD), an inherited, progressive neurodegenerative disorder characterised primarily by involuntary movements. These symptoms are caused by the death of neurons in the basal ganglia, a set of subcortical brain structures involved in the control of movement. One of the genes involved, huntingtin, is found on the short arm of chromosome 4, and the condition is inherited in an autosomal dominant manner. HD is a trinucleotide repeat disease; at one end of the gene, a sequence of 3 DNA bases are repeated multiple times, and mutations in the huntingtin gene cause an increase in the number of repeats. If the number of repeats reaches 40 or above, a mutated form of the Huntingtin protein is synthesized; this mutant protein is somehow involved in the neuronal cell death. Their is a direct correlation between the number of trinucleotide repeats and age of onset of HD – the greater the number of repeats, the earlier the age of onset. Leslie, who writes a blog called Paternal Age and De Novo Single Gene Disorders etc., has submitted the abstract for a 1993 paper about the association between Huntington’s disease mutations and advanced paternal age.
Larry Moran, author of the Sandwalk blog, gives us two posts about blood clotting, a very elegant process that occurs as a result of an intricate biochemical cascade involving more than a dozen proteins. At the heart of the clotting process are two proteins, called fibrinogen and thrombin. Fibrinogen contains a number of adhesive regions which are usually covered up. Thrombin is a protease – an enzyme that snips other proteins. Following an injury, thrombin acts on fibrinogen molecules to expose their adhesive regions, causing them to form an insoluble clump that stems blood flow at the site of injury. In organisms with a simple circulatory system containing relatively low volumes of blood flowing at a low temperature, these two proteins are all that is needed for the clotting reaction. But in the vertebrate lineage, blood flows through its vessels under high pressure and, during the course of evolution, a series of gene duplications resulted in an increased number of clotting factors; as a result, there was a massive amplification of the clotting process, such that a more rapid and efficient response can be generated after the initial stimulus. Larry’s first post is about a number of human anticoagulant genes implicated in various cardiovascular conditions, while the second is about anticoagulants, the chemicals which prevent blood clotting. Larry also submitted a third post, about human genes for the pyruvate hydrogenase complex. The products of these genes form a large enzyme complex that catalyzes a very important reaction – the conversion of pyruvate to acetyl-Coenzyme A, a molecule involved in many biochemical reactions that are crucial to the cell.
We’ll finish with general genetics posts and posts about genes in organisms other than humans. Over at ScienceRoll, Bertalan has two posts; one about genetics in Second Life, the three-dimensional virtual world recently built by internet users, and another containing a slideshow of a recent presentation he gave on genetics and Web 2.0. Grrl Scientist, who blogs at Living the Scientific Life, has a post about a mouse model of bipolar disorder (also known as manic depression). Individuals who suffer from this condition experience dramatic mood swings, in which they cycle between episodes of euphoria and hopelessness. It’s not surprising, then, that a number of the genes implicated in bipolar disorder are expressed in the suprachiasmatic nucleus, where they regulate the circadian rhythm. At Ouroboros, Chris has a post about Sirtuin-2, one of a family of proteins that have been implicated in the extension of life span associated with calory restriction. This phenomenon has most extensively studied in yeast cells and nematode worms, but there are also mammalian versions of the sirtuin genes.
At Sciencesque, Tim discusses the sequencing of the Tyrannosaurus rex collagen protein. This story was big news recently; the surprising similarity between the T. rex protein sequence and that of chickens led most commentators to state that barbequed T. rex would have tasted like chicken! Finally, my contribution is about the evolution of dorso-ventral (D-V) patterning in the developing nervous system. This process is regulated by a highly evolutionarily conserved family of proteins called the BMPs (bone morphogenetic proteins). Research published this week shows that the mechanisms of D-V patterning in the marine ragworm, a “living fossil” thought to most closely resemble the common ancestor of vertebrates, worms and insects, occurs in a very similar way to, and involves exactly the same molecules as, D-V patterning in the zebrafish, which is a vertebrate. The implication is that vertebrates (including humans) may have inherited the organization of their nervous systems from an ancient worm.