Genomics

Mutations in a single gene can cause several types of developmental brain abnormalities that experts have traditionally considered different disorders. With support from the National Institutes of Health, researchers found those mutations through whole exome sequencing – a new gene scanning technology that cuts the cost and time of searching for rare mutations. Whole exome sequencing can be applied to dozens of other rare genetic disorders where the culprit genes have so far evaded discovery. Such information can help couples assess the risk of passing on genetic disorders to their children. It can also offer insights into disease mechanisms and treatments.

Together with colleagues from an international research group, autism researcher Christopher Gillberg of the University of Gothenburg, Sweden, has found in a new study that autism can be partially explained by abnormalities in certain genes. The group's results could, in the long run, pave the way for more appropriate treatments for autism.

In the article the group reveals that a survey of 1,000 individuals with autism and 1,300 without showed that Copy Number Variants (CNVs) sub-microscopic abnormalities in the chromosomes are heavily over-represented in autistic people.

This study analysed the genome-wide characteristics of rare (<1% frequency) copy number variation in ASD using dense genotyping arrays. When comparing 996 ASD individuals of European ancestry to 1,287 matched controls, cases were found to carry a higher global burden of rare, genic copy number variants (CNVs), especially so for loci previously implicated in either ASD and/or intellectual disability. Among the CNVs there were numerous de novo and inherited events, sometimes in combination in a given family, implicating many novel ASD genes such as SHANK2, SYNGAP1, DLGAP2 and the X-linked DDX53–PTCHD1 locus. We also discovered an enrichment of CNVs disrupting functional gene sets involved in cellular proliferation, projection and motility, and GTPase/Ras signaling. Our results reveal many new genetic and functional targets in ASD that may lead to final connected pathways.

New research from the lab of Michael Greenberg, Nathan Marsh Pusey professor and chair of neurobiology at HMS, in collaboration with bioinformatics specialist and neuroscientist Gabriel Kreiman, assistant professor of ophthalmology at Children's Hospital, Boston, has found that a particular set of RNA molecules widely considered to be no more than a genomic oddity are actually major players in brain development - and are essential for regulating the process by which neurons absorb the outside world into their genetic machinery.

Researchers at the University of North Carolina at Chapel Hill School of Medicine have found that the 22q11 gene deletion -- a mutation that confers the highest known genetic risk for schizophrenia -- is associated with changes in the development of the brain that ultimately affect how its circuit elements are assembled.

The researchers would now like to figure out how these alterations in the circuitry of the brain affect the behavior of the mouse. They also hope that understanding the "mis-wiring" of the brain in a genetic animal model of schizophrenia would help them understand the causes of the disease in the general population