Activity of gene in the brain depends on genetic background

WASHINGTON - A new study has revealed that same genes have different activity patterns in the brain in individuals with different genetic backgrounds.

These findings from researchers at the Allen Institute for Brain Science may help to explain individual differences in the effectiveness and side-effect profiles of therapeutic drugs and thus have implications for personalized medicine.

In this study, the authors compared where in the brain each of 49 different pharmaceutically related genes is expressed, or turned on, in seven genetically distinct groups of mice with known genealogical relationships.

By analyzing 203 distinct brain areas over 15,000 thin sections of tissue, they precisely mapped where these genes are active, down to the level of individual cells.

The genes all encode molecular targets of well-known pharmaceuticals, such as antidepressants, antipsychotics and pain relievers including Prozac, Imitrex, and Aricept.

More than half of the genes examined showed striking, localized differences in expression patterns between the different genetic groups, or strains, of mice.

“It is clear that to understand how genes translate to behavioural and other differences between individuals and species, we need to look beyond just the inherited sequences of the genes themselves,” said Allan Jones of the Allen Institute for Brain Science.

“Our results show that genetic background-the specific blend of gene variants comprising an individual genome-can influence how the activity of a given gene is regulated and where it is expressed,” he said.

The date from the study has demonstrated that closer genetic relatives exhibit fewer differences in gene expression patterns, whereas more distant relatives show greater variation.

Interestingly, the researchers found that the expression variations between genetic strains were more likely to be found in areas of the brain that evolved more recently.

“This study shows how large-scale datasets can be used to reveal fundamental biological patterns that would likely be missed otherwise.

“It is likely that many important differences between individuals and species may result from combinations of many small but clear differences in gene expression,” said Jones.

The study was published in the Proceedings of the National Academy of Sciences. (ANI)