Autism Gene Screen Highlights Protein Network

In HHMI,  findings from University of Washington’s Jay Shendure and HHMI investigator Evan Eichler showed that nearly 40 percent of the 125 most deleterious mutations found in patients with autism affected proteins which work in concert in one central hub of interconnected metabolic activity.  This central hub is a control point for numerous developmental processes during cell differentiation and morphological development, such as the upregulation/downregulation of gene expression by the large-scale packaging of DNA, a process called chromatin remodeling.

Autism is understood to be a spectrum of neurological disorder typified by inhibited communication and social skills.  Although it has been long suspected that autistic syndromes are congenital, the exact genetic and biochemical interplay that causes the disease state remained poorly understood, with dozens to hundreds of genes implicated in its epidemiology.

However, in the latest research findings, Eichler and his colleagues studied data from the Simons Simplex Collection wherein only one member from a genealogical pedigree had autism.  The presumption became that since only one progeny had autism, then the mutation which led to the disease state was spontaneous and only occurred in the germ line of the parents, most often the father.  "By comparing the genetics of the parents, who don’t have autism, and the child who does, researchers can spot genetic differences and narrow down the list of mutations that could be responsible for the disorder in that individual."  The analysis of the Simons Simplex Collection data showed that the mutations which led to autism all involved proteins that were interconnected in a single metabolic activity hub that functioned as a control point for cell differentiation.

Further research is required to fully understand autism and its umbrella of neurological disease state, but the recent findings published in HHMI give scientists a vital staging point for their research and inquiries.

[caption id="attachment_5152" align="aligncenter" width="1051" caption="Metabolic flux."][/caption]