Amazing Science

The Cancer Genome Atlas' 1st Annual Scientific Symposium November 17-18, 2011 - Watch the meeting online!

INTO THE MIDDLE EAST - 150,000 to 125,000 years ago.

The global migration began when modern humans left Africa and crossed the Sinai or the base of the Red Sea. Fossils in Israel record their presence, and a 2011 discovery in Arabia suggests that by 125,000 years ago, modern humans had reached the doorstep of Asia.

ASIAN EXPANSION - 125,000 to 50,000 years ago.

Modern humans may have crossed into Asia as far back as 125,000 years ago and reached India before the eruption of Toba 74,000 years ago. An alternative view holds that humans colonized Asia no earlier than 60,000 years ago by spreading rapidly along the coast of the Indian Ocean.

EUROPEAN MIGRATION - 50,000 to 20,000 years ago.

Better purification techniques in radiocarbon dating have pushed back the arrival of the earliest humans in Europe to 45,000 years ago, 5,000 years earlier than was thought, and may shed light on when and how they interacted with Neanderthals.

JOURNEY TO AMERICA - 20,000 to 10,000 years ago.

Archaeological remains and genetic clues suggest that modern humans left Siberia and made it to North America more than 14,000 years ago, at the end of the last ice age. Researchers debate whether the colonists walked down through central Canada or skirted the coast in boats. A controversial hypothesis suggests that the first Americans came from Europe by boat.

There are approximately 30 genes that were selectively duplicated in humans - some of our most recent genomic innovations. Intriguingly, many of these genes appear to play some role in the developing brain. Franck Polleux and Evan Eichler, genome scientists at the University of Washington, focused their expertise and attention on one of the genes known as SRGAP2. This gene has, in fact, been duplicated at least twice during the course of human evolution, first about 3.5 million years ago and then again about 2.5 million years ago.

Interestingly, the novel gene appears to have arisen just as the fossil record shows a transition from human's extinct Australopithecus ancestors to the genus Homo (as in Homo sapiens), which led to modern humans. That's also when the brains of our ancestors began to expand and when dramatic changes in cognitive abilities are likely to have emerged.

The researchers don't think SRGAP2 is solely responsible for that brain expansion, but the genetic interference does have potential benefits. Polleux and colleagues mimic the function of the human-specific SRGAP2 duplication in mice. They show that loss of SRGAP2 function accelerates neurons' migration in the developing brain, potentially helping them reach their final destination more efficiently. Moreover, neurons that have decreased SRGAP2 function, due to expression of the human-specific SRGAP2 display more knob-like extensions or spines on their surfaces, making the neurons appear much more like those found in the human brain. These spines enable connections between neurons to form.

The key to treating one of the most common types of human leukemia may lie within mutations in a gene called FLT3, according to new research led by physician-scientists at the University of California, San Francisco (UCSF) Helen Diller Family Comprehensive Cancer Center.

Researchers have identified two genes that affect brain size and may be linked not only to IQ, but also to our risk of developing brain disorders like Alzheimer’s disease.

Scientists have known for some time that the size and volume of certain parts of the brain are linked to disorders including developmental conditions such as autism and degenerative diseases like Alzheimer’s. The brains of autistic children, for example, tend to be bigger than those of unaffected youngsters, and in Alzheimer’s patients, the brain region responsible for memory, the hippocampus, tends to be smaller.

Read more: http://tinyurl.com/73d65oc

A group of researchers found a unique viral genome that has never before been reported - a circular, single-stranded DNA virus encoding a major capsid protein seen previously only in RNA viruses. This unusual genome provides proof that integration of an RNA virus into a DNA virus may have occurred between two unrelated virus groups at some point in evolution - something that has not been observed before. Moreover, this suggests that entirely new virus types may emerge via recombination of functional and structural modules between vastly different viruses, using mechanisms that are as-yet unknown. The team observed that the Boiling Springs Lake RNA-DNA hybrid virus (BSL RDHV) genome is circular, but its size is roughly double that of typical circoviruses, with the ORFs arranged in an uncommon orientation. They compared the BSL RDHV genome to other metagenomic DNA sequences from the Global Ocean Survey, and found strong evidence to conclude that previously undetected BSL RDHV-like viruses could be widespread in the marine environment and are likely to be found in other environments as well.

The answer is, of course, that curing a single cancer, much less many cancers, is really, really hard. Scientists not only have to contend with basically a continuous spectrum of mutations between individual cancers that renders the concept of even single cancer subtypes horribly naive, but with a near continuous spectrum of mutations between groups of cells in a single tumor.

There is reason for hope, however. As was discussed at AACR 2012, the vast majority of cancer-causing driver mutations can be divided into 12 key molecular signaling pathways, and mutations at the “trunk” of the divergent branching evolution tend to remain as divergent evolution occurs, and targeting them is likely to be more effective than targeting mutations further out on the branches. It might be possible to hone in on these different pathways. In the meantime, as the cost of sequencing continues to fall, it might become feasible to sequence several parts of a tumor and its metastases and map out treatments that cover all of them. Personalized medicine is thus possible and still holds promise. It’s just not going to be as simple as getting a biopsy of a tumor and picking a targeted agent or two to blast the tumor into oblivion. The point is not that personalized medicine is impossible or that it’s impossible to develop cures for various cancers. The point is that biology is always way more complicated than we ever thought it was, and evolution almost always wins out. Even so, the reason we haven’t cured cancer yet is because we haven’t figured out how to overcome the power of evolution. Until we figure out a way to do that, we will continue to make only incremental progress.

Horses were domesticated 6,000 years ago on the grasslands of Ukraine, southwest Russia and west Kazakhstan, a genetic study shows. Domestic horses then spread across Europe and Asia, breeding with wild mares along the way.

TYRP1 is known to be involved in skin and hair pigmentation in several species. In normally black mice, for example, a mutation in the gene produces light brown coats. A rare kind of human albinism is also caused by mutations in TYRP1, which produces reddish skin colour and ginger hair. TYRP1 isn't, however, one of the genes that produces blond hair in Europeans. The novel blond mutation in Solomon Islanders is likely to have cropped up around 10,000 years ago, and it appears to be the same one behind blondness in Fiji and other regions of the South Pacific.

http://tinyurl.com/d5gpp7b

The Genomics in Medicine Lecture Series is sponsored by NHGRI, in collaboration with Suburban Hospital and Johns Hopkins. Each lecture takes place at Suburban Hospital's lower level auditorium at 8600 Old Georgetown Road in Bethesda, Md. All are welcome to the hour-long lectures, which begin at 8 a.m. on the first Friday of the month, from December 2011 through June 2012.

Scientists have identified a gene (USP9X) that slows the spread of pancreatic cancer tumours, paving the way for targeted treatment of one of the deadliest forms of the disease. After discovering the gene USP9X at work in a study of pancreatic cancer in mice, the international research team found it also played a role in humans. USP9X is a member of the peptidase C19 family and encodes a protein that is similar to ubiquitin-specific proteases. Though this gene is located on the X chromosome, it escapes X-inactivation. Mutations in this gene have been associated with Turner syndrome. Alternate transcriptional splice variants, encoding different isoforms, have also been characterized.

Deubiquitinases play an important role regulatory role at the level of protein turnover by preventing degradation of proteins through the removal of conjugated ubiquitin and are an essential component of TGF-beta/BMP signaling cascade. They influence chromosome alignment and segregation in mitosis by regulating the localization of BIRC5/survivin to mitotic centromeres. Specifically hydrolyzing both 'Lys-29'- and 'Lys-33'-linked polyubiquitins chains and deubiquitinating mono-ubiquitinated SMAD4, opposing the activity of E3 ubiquitin-protein ligase TRIM33.

Scientists have discovered a striking association between genes found disrupted in children with autism and genes that are targets of FMRP, the protein generated by the gene FMR1, whose dysfunction causes Fragile-X syndrome.

Long stretches of DNA are currently created in a costly and time-consuming manner by stitching together short strings of nucleic acids known as oligonucleotides. Where the bottleneck occurs -- and where the expense mounts -- is in the production of the smaller building blocks, called oligonucleotides. Recent technological advances, discussed here by Wyss researcher Sriram Kosuri, have made it possible to create hundreds of thousands of these oligonucleotides on a single DNA microchip, resulting in a low-cost, reliable gene-synthesis technology.

A Pulitzer Prize-winning series of articles by Amy Harmon exploring the impact of new genetic technology on American life. E-mails to Amy Harmon about this series may be sent to: dna@nytimes.com

Medical geneticists are giving genome sequencing its first big test in the clinic by applying it to some of their most baffling cases. By the end of this year, hundreds of children with unexplained forms of intellectual disability and developmental delay will have had their genomes decoded as part of the first large-scale, national clinical sequencing projects.

Fast forwarding to the near future and based on the recent past, sequencing instrument companies will continue to develop more user-friendly and cheaper technology, focused on the benchtop and clinical markets. Manufacturers will also continue to form partnerships and make acquisitions that place heavy bets on completely novel, potentially disruptive sequencing technologies.

By far the largest market opportunity, though, is in emerging applications of personal genomics and clinical diagnostics. These segments are expected to account for $541 million by 2015 from $15.5 million in 2010, representing a CAGR of 103.5%.

Recent advancements in the field of next-generation sequencing have resulted in the advent of so-called personal genome machines (PGMs), smaller-scale, benchtop genome sequencers marketed by Illumina (MiSeq), Life Technologies (Ion Torrent), and Roche 454 (GS Junior). Companies like Diagnomics ( http://www.diagnomics.com ) provide sophisticated annotation.