Posts tagged genomics
Articles and news from the latest research reports.
The zebrafish is a major player in the study of vertebrate biology and human disease. Its transparent, externally fertilized eggs, short reproductive cycle and fast growth mean that its embryonic development can be studied closely while the animal is alive, and the fish is a useful model for studying gene behaviour and function.
Now, researchers led by Stephen Ekker, a molecular biologist at the Mayo Clinic in Rochester, Minnesota, have for the first time made custom changes to parts of the zebrafish (Danio rerio) genome, using artificial enzymes to cut portions of DNA out of targeted positions in a gene sequence, and replace them with synthetic DNA.
Dark matter DNA active in brain during day — night cycle
NIH study of rats shows DNA regions thought inactive highly involved in body’s clock
Long stretches of DNA once considered inert dark matter appear to be uniquely active in a part of the brain known to control the body’s 24-hour cycle, according to researchers at the National Institutes of Health.
Working with material from rat brains, the researchers found some expanses of DNA contained the information that generate biologically active molecules. The levels of these molecules rose and fell, in synchrony with 24-hour cycles of light and darkness. Activity of some of the molecules peaked at night and diminished during the day, while the remainder peaked during the day and diminished during the night.
Researchers have long known that individual diseases are associated with genes in specific locations of the genome
Genetics researchers at the University of North Carolina at Chapel Hill now have shown definitively that a small number of places in the human genome are associated with a large number and variety of diseases. In particular, several diseases of aging are associated with a locus which is more famous for its role in preventing cancer.
For this analysis, researchers at UNC Lineberger Comprehensive Cancer Center catalogued results from several hundred human Genome-Wide Association Studies (GWAS) from the National Human Genome Research Institute. These results provided an unbiased means to determine if varied different diseases mapped to common ‘hotspot’ regions of the human genome. This analysis showed that two different genomic locations are associated with two major subcategories of human disease.
“Our team is interested in understanding genetic susceptibility to diseases associated with aging, including cancer,” said PhD student William Jeck, who was first author on the study, published in the journal Aging Cell.
First extensive analysis of Allen Human Brain Atlas published in Nature has implications for basic understanding of the human brain and for medicine
Scientists at the Allen Institute for Brain Science reported in the latest issue of the journal Nature that human brains share a consistent genetic blueprint and possess enormous biochemical complexity. The findings stem from the first deep and large-scale analysis of the vast data set publicly available in the Allen Human Brain Atlas.
The results of this study are based on extensive analysis of the Allen Human Brain Atlas, specifically the detailed all-genes, all-structures survey of genes at work throughout the human brain. This dataset profiles 400 to 500 distinct brain areas per hemisphere using microarray technology and comprises more than 100 million gene expression measurements covering three individual human brains to date. Among other findings, these data show that 84% of all genes are expressed somewhere in the human brain and in patterns that are substantially similar from one brain to the next.
"This study demonstrates the value of a global analysis of gene expression throughout the entire brain and has implications for understanding brain function, development, evolution and disease," said Ed Lein, Ph.D., Associate Investigator at the Allen Institute for Brain Science and co-lead author on the paper. "These results only scratch the surface of what can be learned from this immense data set. We look forward to seeing what others will discover."
Small genetic change has heavy consequences
One small change to the DNA sequence can cause more weighty changes to the human body, according to a new study released today. The discovery comes thanks to a worldwide consortium of researchers that includes Professor and Chair of Quantitative Genetics at The University of Queensland (UQ), Peter Visscher, from the Queensland Brain Institute (QBI) and Diamantina Institute (DI) at UQ.
He and his team have found a single change in genetic sequence at the gene FTO had a significant effect on the variability of body mass index (BMI). BMI is a commonly used measure of obesity. It measures someone’s weight adjusted for his or her height.
Professor Visscher said that the genetic change, called a single nucleotide polymorphism (SNP), was the replacement of one nucleotide – the units that make up our DNA – with another. “They are the most abundant type of variation in the human genome,” he said. “SNPs occur normally throughout our DNA and most have no effect on our health, however, we’ve found one that does have a small but significant effect on variation in BMI.”
After analysing data from almost 170,000 people, he and his team established that those with a sequence variant in the FTO gene not only weighed more on average, but the measured weights varied more than in the group without the variant. The variability of BMI within the group with two copies of the variant was, in fact, 7 per cent larger than the group without the variant.
Professor Visscher said this equated to around half a kilogram difference in the standard deviation of weight. “So as a group, people with two copies of the weight increasing variant are a few kilograms heavier and vary more,” he said. Genetic differences in variability of specific traits have been seen in many plant and animal species but specific genes or mechanisms to explain the phenomenon had not been identified.
Professor Visscher’s study is the first to look systematically at genetic effects on variation of a complex trait in humans using a very large sample size. “The study is important because it demonstrates that genes can be found that affect trait variability. “This is a first step towards understanding how genes control variation,” Professor Visscher said.
This study is also the first to offer researchers an indirect method to measure genotype by environment interactions without having a measure of specific environmental factors. “If a gene interacts with specific environmental factors then this can be observed with our method,” Professor Visscher said.
“For example, if the effect of a gene on weight is smaller in people who physically exercise than in people who do not, then this will lead to less variation among people with two copies of the weight decreasing variant.
“In our study we did not measure specific environmental effects such as physical exercise so we can’t say for sure whether our results are due to a genotype-environment interaction.”
This is the second study Professor Visscher has published in the prestigious journal Nature this year. Earlier this year he identified that genetic differences also affect how intelligence changes across a lifetime. The work also suggested these changes in intelligence were largely influenced by environmental factors.
(Source: uq.edu.au)
This is how a heart becomes a heart
A “synchronised dance” of thousands of genes generates a healthy heart, but one faux pas may result in congenital heart defects.
Congenital heart defects (CHD) are one of the most common birth abnormalities in the world. In Australia six babies are born with a heart disease every day and more than 32,000 children under the age of 18 live with a CHD, but a team of researchers at the Gladstone Institutes have found the genetic switches that translate as a functional heart.
Using next-generation DNA sequencing and stem cell technology, the researchers were able to decipher the genomic blueprint (the instruction manual) of a heart. The finding will help understand how certain CHDs such as holes in the heart (septal defects) are formed. “Congenital heart defects are the most common type of birth defects,” said Gladstone Senior Investigator Benoit Bruneau to UCFS news. “But how these defects develop at the genetic level has been difficult to pinpoint because research has focused on a small set of genes. Here, we approach heart formation with a wide-angle lens by looking at the entirety of the genetic material that gives heart cells their unique identity.”
![According to ENCODE’s analysis, 80 percent of the genome has a “biochemical function”. More on exactly what this means later, but the key point is: It’s not “junk”.
Scientists have long recognised that some non-coding DNA has a function, and more and more solid examples have come to light [edited for clarity - Ed]. But, many maintained that much of these sequences were, indeed, junk. ENCODE says otherwise. “Almost every nucleotide is associated with a function of some sort or another, and we now know where they are, what binds to them, what their associations are, and more,” says Tom Gingeras, one of the study’s many senior scientists.
And what’s in the remaining 20 percent? Possibly not junk either, according to Ewan Birney, the project’s Lead Analysis Coordinator and self-described “cat-herder-in-chief”. He explains that ENCODE only (!) looked at 147 types of cells, and the human body has a few thousand. A given part of the genome might control a gene in one cell type, but not others. If every cell is included, functions may emerge for the phantom proportion. “It’s likely that 80 percent will go to 100 percent,” says Birney. “We don’t really have any large chunks of redundant DNA. This metaphor of junk isn’t that useful.”
That the genome is complex will come as no surprise to scientists, but ENCODE does two fresh things: it catalogues the DNA elements for scientists to pore over; and it reveals just how many there are. “The genome is no longer an empty vastness – it is densely packed with peaks and wiggles of biochemical activity,” says Shyam Prabhakar from the Genome Institute of Singapore. “There are nuggets for everyone here. No matter which piece of the genome we happen to be studying in any particular project, we will benefit from looking up the corresponding ENCODE tracks.”](http://41.media.tumblr.com/tumblr_m9y0xaewSN1rog5d1o1_500.jpg)
According to ENCODE’s analysis, 80 percent of the genome has a “biochemical function”. More on exactly what this means later, but the key point is: It’s not “junk”.
Scientists have long recognised that some non-coding DNA has a function, and more and more solid examples have come to light [edited for clarity - Ed]. But, many maintained that much of these sequences were, indeed, junk. ENCODE says otherwise. “Almost every nucleotide is associated with a function of some sort or another, and we now know where they are, what binds to them, what their associations are, and more,” says Tom Gingeras, one of the study’s many senior scientists.
And what’s in the remaining 20 percent? Possibly not junk either, according to Ewan Birney, the project’s Lead Analysis Coordinator and self-described “cat-herder-in-chief”. He explains that ENCODE only (!) looked at 147 types of cells, and the human body has a few thousand. A given part of the genome might control a gene in one cell type, but not others. If every cell is included, functions may emerge for the phantom proportion. “It’s likely that 80 percent will go to 100 percent,” says Birney. “We don’t really have any large chunks of redundant DNA. This metaphor of junk isn’t that useful.”
That the genome is complex will come as no surprise to scientists, but ENCODE does two fresh things: it catalogues the DNA elements for scientists to pore over; and it reveals just how many there are. “The genome is no longer an empty vastness – it is densely packed with peaks and wiggles of biochemical activity,” says Shyam Prabhakar from the Genome Institute of Singapore. “There are nuggets for everyone here. No matter which piece of the genome we happen to be studying in any particular project, we will benefit from looking up the corresponding ENCODE tracks.”
Researchers have discovered two gene variants that raise the risk of the pediatric cancer neuroblastoma. Using automated technology to perform genome-wide association studies on DNA from thousands of subjects, the study broadens understanding of how gene changes may make a child susceptible to this early childhood cancer, as well as causing a tumor to progress.
“We discovered common variants in the HACE1 and LIN28B genes that increase the risk of developing neuroblastoma. For LIN28B, these variants also appear to contribute to the tumor’s progression once it forms,” said first author Sharon J. Diskin, PhD, a pediatric cancer researcher at The Children’s Hospital of Philadelphia. “HACE1 and LIN28B are both known cancer-related genes, but this is the first study to link them to neuroblastoma.”
Diskin and colleagues, including senior author John M. Maris, MD, director of the Center for Childhood Cancer Research at Children’s Hospital, published the study online Sept. 2 in Nature Genetics.
High quality Denisovan genome sheds light on human evolution: Sequencing our extinct relatives let us know how we differ from chimps.
The discovery that a second branch of the human family shared Asia with our ancestors and the Neanderthals was a real shock, but the Denisovans have continued to surprise many. All we have of them is a bit of a finger and some molars, but those few fragments have yielded a wealth of DNA, and with it the knowledge that the Denisovans interbred with the ancestors of some modern human populations. Now, with the help of a new approach to sequencing ancient DNA, we actually know more about the Denisovans’ genome than we do about Neanderthals’. In the process, we’ve discovered some of the changes that are distinct to modern humans.
Expectant mothers are used to fuzzy images on ultrasound monitors and blood tests to screen for potential health problems in their unborn babies. But what if one of those blood tests came back with a readout of the baby’s entire genome? What if a simple test gave parents every nuance of a baby’s genetic makeup before birth?
Recent studies show that it’s possible to decode an entire fetal genome from a sample of the mother’s blood. In the future, doctors may be able to divine a wealth of information about genetic diseases or other characteristics of a fetus from the pregnant mother’s blood. Such tests will raise ethical questions about how to act on such information. But they could also lead to research on treating diseases before birth, and leave parents and their doctors better prepared to care for babies after birth.