Washington, November 25 (ANI): Short snippets of DNA found in human brain tissue have provided new insight into human cognitive function and risk for developing certain neurological diseases, researchers from the Departments of Psychiatry and Neuroscience at Mount Sinai School of Medicine have revealed.
There are nearly 40 million positions in the human genome with DNA sequences that are different than those in non-human primates, making the task of learning which are important and which are inconsequential a challenge for scientists.
Rather than comparing these sequences strand by strand, Schahram Akbarian, MD, PhD, Professor of Psychiatry and Neuroscience at Mount Sinai School of Medicine, wanted to identify the crucial set of differences between the two genomes by looking more broadly at the chromatin, the structure that packages the DNA and controls how it is expressed.
They found hundreds of regions throughout the human genome, which showed a markedly different chromatin structure in neurons in the prefrontal cortex, a brain region that controls complex emotional and cognitive behaviour, compared to non-human primates. The findings of the study provide important insights for diseases that are unique to humans such as Alzheimer's disease and autism.
"While mapping the human genome has taught us a great deal about human biology, the emerging field of epigenomics may help us identify previously overlooked or discarded sequences that are key to understanding disease," said Dr. Akbarian.
"We identified hundreds of loci that represent untapped areas of study that may have therapeutic potential," he stated.
Dr. Akbarian and his research team isolated small snippets of chromatin fibers from the prefrontal cortex. Next, they analyzed these snippets to determine what genetic signals they were expressing. Many of the sequences with human-specific epigenetic characteristics were, until recently, considered to be "junk DNA" with no particular function.
Now, they present new leads on how the human brain has evolved, and a starting point for studying neurological diseases. For example, the sequence of DPP10-a gene critically important for normal human brain development-not only showed distinct human-specific chromatin structures different from other primate brains such as the chimpanzee or the macaque, but the underlying DNA sequence showed some interesting differences from two extinct primates-the Neanderthal and Denisovan, most closely related to our own species and also referred to as 'archaic hominins'.
"Many neurological disorders are unique to human and are very hard as a clinical syndrome to study in animals, such as Alzheimer's disease, autism, and depression. By studying epigenetics we can learn more about those unique pieces of the human genome," said Dr. Akbarian.
The research team also discovered that several of these chromatin regions appear to physically interact with each other inside the cell nucleus, despite being separated by hundreds of thousands of DNA strands on the genome. This phenomenon of "chromatin looping" appears to control the expression of neighbouring genes, including several with a critical role for human brain development.
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Short DNA strands in human genome could shed light on Alzheimer's and autism
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