A large-scale study headed by Yale University researchers has found that most genes associated with psychiatric illnesses are expressed before birth in the developing human brain. In addition, the researchers found hundreds of genetic differences between males and females as their brains take shape in the womb.
The study identified genes expressed in the human brain, and when and where in the brain they were expressed. The researchers analyzed 1,340 tissue samples taken from 57 subjects aged from 40 days after conception to 82 years.
The study appears in the journal Nature, October 27, 2011.
The creation of a hundred billion brain cells and the incalculable number of connections between them is such a complex task that 86 percent of 17,000 human genes studied are involved in the process. The study tracked not only what genes are involved in development, but where and when they are expressed, or activated.
Nenad Sestan, a neurobiologist and senior author of the study, said:
We knew many of the genes involved in the development of the brain, but now we know where and when they are functioning in the human brain. The complexity of the system shows why the human brain may be so susceptible to psychiatric disorders.
The researchers’ analysis of 1.9 billion data points gives an unprecedented map of genetic activity in the brain at different stages of development. In dramatic fashion, the findings show just how much of the human brain is shaped prior to birth.
For instance, the team analyzed genes and variants previously linked with autism and schizophrenia, the symptoms of which are evident in the first few years of life or during early adulthood, respectively. The new analysis shows molecular evidence of expression of these suspect genes prior to birth.
We found a distinct pattern of gene expression and variations prenatally in areas of the brain involving higher cognitive function. It is clear that these disease-associated genes are developmentally regulated.
The team also looked for differences in brains of males and females. They expected to find clear differences in Y chromosome genes that are possessed only by males. However, they also demonstrated that men and women showed distinct differences in many genes that are shared by both sexes – both in whether the gene was expressed and the level of the gene’s activity. Most of the differences were noted prenatally.
Bottom line: A study led by neurobiologist Nenad Sestan of Yale University showed that most genes associated with mental illnesses are expressed before birth in the developing human brain. The study also found genetic differences between males and females as their brains develop prenatally. Results of the study appear in the October 27, 2011, issue of Nature.
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