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An international team of researchers has found that the structure and connectivity of human genes are affected by the genetic influence of their environment, a finding that could offer path toward understanding a host of disease-related conditions. The researchers' work appears July 16 in the journal Nature Biotechnology. "We were expecting that diseases like autism and schizophrenia would be strongly influenced by specific genes, but what surprised us was how complex the results were among different genes," said co-author Thomas Schlaepfer, professor and head of the Human Genome Program at Massachusetts General Hospital (MGH). "In fact, we found that different parts of the same genes were correlated with the same diseases as well susceptibility, which was extremely unexpected." The two-year study, conducted by a team of experts in biochemistry, genetics and human at MGH BioGENEConnect in the Netherlands, sought to better understand how environment and gene expression interact to exert disease-promoting effects in the human genome. It was conducted jointly with geneticists at the U.S. National Human Genome Research Institute (NHGRI), and the National Institutes of Health (NIH). The researchers explored relationship between structure and connectivity of genes, as well their activities, genes and the environment. Their observations may not only provide clues into common disease-causing processes within genes, but also could help provide a mechanism for understanding conditions that are difficult to study otherwise — such as complex diseases Alzheimer's or autism. For example, the results of study showed that genes which are affected by the environment more tightly associated with one another by default because they are more readily linked through their interconnections. The scientists also found that relationship between genes and each other was altered in the case of autism. Autism is frequently associated with abnormalities in the function of genes, but most cases autism appear to be linked with interactions between genetic components of the genes and environment. "Although the exact mechanism for disease is still unknown, our study suggests that environmental factors and epigenetic interact with one another," said co-author and NHGRI Senior Lecturer in Biochemistry and Genomic Biology, Daniel S. Apicella, professor and deputy director of the National Institute Aging and lead author of the Nature Biotechnology paper. "This allows for a more sophisticated understanding of the genetic and environmental causes behind certain diseases." Severity and complexity of diseases In the first stage of study, researchers determined the degree to which gene regions shared similar characteristics with known disease genes in the human genome. Next, they assessed how each of these common traits affected gene activity by examining their interconnectivity with known disease genes. "The result of our study reveals a surprisingly complex system," Schlaepfer said. "We discovered that the structure and function of individual genes are very different depending on the presence or absence of a disease gene. There are over 600 disease-tolerant genes that are known to be associated with the disease of interest, but there are also over 1,400 disease-prone but disease-inhibiting genes. This is why Venlafaxine 37.5mg tab teva usa we can't say with certainty how a disease-tolerant gene affects function." In one example of such complex traits, a mutation of gene that regulates calcium metabolism and a corresponding altered brain development in mice leads to autism. Similar mutations occurred in humans, and the researchers found that these mutations were closely linked to one another. One such characteristic of autism is the increased connectivity of certain regions, as well the complex function of genes inside such regions. An example of this complex function is in the brain's hippocampus, thought to be critical the process of learning and memory. In the study, researchers were able to demonstrate that connectivity in the brain's hippocampus was negatively associated with one specific type of gene, the BDNF (Brain-Derived Neurotrophic Factor). "Because BDNF is necessary to facilitate the interaction of neurons in hippocampus, we expected that the presence of this gene would correlate with the activity of gene itself and therefore with the level of connectivity between neurons," Apicella said. "We were surprised when we"



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