TUESDAY, MARCH 20, 2012
An Advance in the Genetics Underlying Autism
I recently read an interesting article published in Biological Psychiatry by Yale researchers Abha Gupta & Matthew State about new advances in the genetics of autism. Autism is a hereditary disorder that belongs to a group known as Autism Spectrum Disorders (ASDs). Children express signs of autism such as language deficiencies, developmental abnormalities, repetitive behaviours and impairments in social communication and interaction at the age of three or younger.
Up until the late 20th century, there was little understood about what caused children to be born with autism. Sequencing of the human genome however, and increases in the efficiency of genomic technologies have significantly increased the understanding of the disorder. Based on this, scientists have been able to discover the molecular and cellular origins of ASDs based from gene identification.
Based on observations from the patterns of inheritance within immediate and extended family members; Gupta & State found that ASDs were not the result of a single gene transmitted in a simple dominant, recessive or x-linked fashion.
To further understand the pathophysiology of autism, Gupta & State undertook an approach called Linkage studies. This process determines whether there is a correlation between the transmission of a chromosomal segment amongst generations, and the phenotype of interest. In Gupta & State’s study, they used a sib-pair study, whereby siblings with ASDs were examined to determine whether any regions of their genome were shared more commonly than as if by chance.
Now this is what gets interesting! The patterns that Gupta & State observed from these analyses, identified regions located on chromosome 7 that showed a significant relationship to ASDs. Evidence supporting this included the identification of rearrangements within chromosome 7q in patients with ASDs. Known functions of chromosome 7q, a chromosome to where several brain-expressed transcripts have been mapped, are potentially linked to the pathophysiology of ASDs; this includes the Engrailed-2 (EN2) gene.
Development of the cerebellum foliation pattern is attributable to the involvement of the homeodomain gene, EN2. When Gupta & State undertook testing on mice that lacked the EN2 coded protein, the mice developed a cerebellar foliation pattern with decreases in the number of cells in their cerebellar circuits. Transgenic mice overexpressing EN2 in Purkinje cells developed an incomplete cerebellum with a reduced number of Purkinje cells and there were disruptions to their banding patterns. These exact same defects were similar to the results of Gupta & State’s histopathologic observations of ASD in humans.
This basically sums up just one of the advancements that Gupta & State found in their research of the genetics underlying autism. Quite interesting I thought, for a condition that is still widely unknown!