Researchers give new insight into human cognition, brain disorders

WASHINGTON: Researchers from the National Institutes of Health (NIH) employed computer modelling to identify mutations in the human genome that are likely to have altered the evolution of human intellect. This pioneering human genomics study might lead to a greater knowledge of human health and the development of innovative therapies for complicated brain illnesses.

The findings of the study were published in Science Advances.

Human intellect is a distinguishing aspect of human evolution that distinguishes humans from other apes. Despite the fact that there have been over 100 million mutations since the human-chimp split, only a small percentage of these have been shown to be relevant. Researchers from the National Library of Medicine (NLM) and the National Cancer Institute (NCI) developed an artificial intelligence (AI) model of gene regulation in the human brain to help them traverse this huge terrain of genetic alterations. The model discovered hundreds of mutations that are likely influencing neocortical development and enhancing mathematical ability acquisition via changed brain gene regulatory pathways.

When the human genome was sequenced in 2001, researchers learned that only 2% of the sequence of our genome is used for coding genes that, in turn, translate into proteins. This is the sequence information that is being used by every single cell. The function of the other 98% of our DNA — often referred to as “noncoding DNA” — remains relatively unknown. It is believed that 95% of disease associations hide within these noncoding parts of our genome.

The research group of Ivan Ovcharenko, PhD, senior investigator in the Computational Biology Branch of NLM’s Intramural Research Program teamed up with the research group of Sridhar Hannenhalli, PhD, senior investigator in NCI’s Center for Cancer Research to create an AI model that measures the effect of noncoding genome mutations on human brain function and development. This led to the identification of a group of noncoding mutations disrupting brain regulatory pathways and potentially causing various complex brain disorders, including autism.

“There are treasure islands within the sea of noncoding DNA in the human genome that are critically important for regulating human genes,” said Dr. Ovcharenko. “Mutations in these regions are largely benign, but there is a class of mutations which detrimentally impact the function of regulatory regions in the brain and affect cellular activity there. By being able to address the impact of individual mutations, we are advancing towards understanding the mechanism of complex diseases and disorders and paving the way for the development of novel therapeutic approaches.”