Tiny Variation in One Gene May Have Led to Brain Convolutions

The human brain has yet to explain the origin of one its defining features – the deep fissures and convolutions that increase its surface area and allow for rational and abstract thoughts. An international collaboration of scientists from the Yale School of Medicine and Turkey may have discovered an important clue – a tiny variation within a single gene that determines the formation of brain convolutions – they report online on May 15, 2011, in Nature Genetics. A genetic analysis of a Turkish patient whose brain lacks the characteristic convolutions in part of his cerebral cortex revealed that the deformity was caused by the deletion of two genetic letters from three billion in the human genetic alphabet. Similar variations of the same gene, called laminin gamma 3 (LAMC3), were discovered in two other patients with similar abnormalities. "The demonstration of the fundamental role of this gene in human brain development affords us a step closer to solve the mystery of the crown jewel of creation, the cerebral cortex," said Dr. Murat Gunel, senior author of the paper and the Nixdorff-German Professor of Neurosurgery, co-director of the Neurogenetics Program and professor of genetics and neurobiology at Yale. The folding of the brain is seen only in mammals with larger brains, such as dolphins and apes, and is most pronounced in humans. These fissures expand the surface area of the cerebral cortex and allow for complex thought and reasoning without taking up more space in the skull. Such foldings aren't seen in mammals such as rodents or other animals. Despite the importance of these foldings, no one has been able to explain how the brain manages to create them. The LAMC3 gene – involved in cell adhesion that plays a key role in embryonic development – may be crucial to the process.