Scientists at Cold Spring Harbor Laboratory (CSHL) have discoveredthat one of the most common genetic alterations in autism - deletion of a 27-gene cluster on chromosome 16 - causesautism-like features. By generating mouse models of autism using atechnique known as chromosome engineering, CSHL Professor AleaMills and colleagues provide the first functional evidence thatinheriting fewer copies of these genes leads to features resemblingthose used to diagnose children with autism. The study appears inthe Proceedings of the National Academy of Sciences in the early online edition during the week of October 3. "Children normally inherit one copy of a gene from each parent. Wehad the tools to see whether copy number changes found in kids withautism were causing the syndrome," explains Mills. In 2007,Professor Michael Wigler, also at CSHL, revealed that some childrenwith autism have a small deletion on chromosome 16, affecting 27genes in a region of our genomes referred to as 16p11.2. Thedeletion - which causes children to inherit only a single copy ofthe 27-gene cluster - is one of the most common copy numbervariations (CNVs) associated with autism. "The idea that this deletion might be causing autism was exciting,"says Mills. "So we asked whether clipping out the same set of genesin mice would have any effect." After engineering mice that had a chromosome defect correspondingto the human 16p11.2 deletion found in autism, Mills and her teamanalyzed these models for a variety of behaviors, as the clinicalfeatures of autism often vary widely from patient to patient, evenwithin the same family. "Mice with the deletion acted completely different from normalmice," explains Guy Horev, a Postdoctoral Fellow in the Millslaboratory and first author of the study. These mice had a numberof behaviors characteristic of autism: hyperactivity, difficultyadapting to a new environment, sleeping deficits, and restricted,repetitive behaviors. Interestingly, mice that had been engineered to carry an extracopy, or duplication, of the 16p11.2 region did not have thesecharacteristics, but instead, had the reciprocal behaviors. Foreach behavior, the deletion had a more dire consequence than theduplication, indicating that gene loss was more severe. This mightexplain why 16p11.2 duplications are detected much more frequentlythan deletions within the human population, and why patients with16p11.2 deletions tend to be diagnosed earlier than those withduplications. The mouse models also revealed a potential link between 16p11.2deletion and survival, as about half the mice died following birth.Whether these findings extend to the human population might beanswered by future studies that investigate the link between thisdeletion and unexplained cases of infant death. The researchers also used MRI to identify specific regions of thebrain that were altered in the autism models, revealing that eightdifferent parts of the brain were affected. The group is nowworking to identify which gene or group of genes among the 27 thatare located within the deleted region is responsible for thebehaviors and brain alterations observed. "Alea Mills has created a valuable resource for everyone engaged inautism research. The technical skill is extraordinary in creatingmouse models bearing a human genetic variant that has beenassociated with autism," says Dr. Gerald Fischbach, Director ofLife Sciences and Simons Foundation Autism Research Initiative(SFARI). These mice will be invaluable for pinpointing the genetic basis ofautism and for elucidating how these alterations affect the brain.They could also be used for inventing ways to diagnose childrenwith autism before they develop the full-blown syndrome, as well asfor designing clinical interventions. Additional References Citations. I am an expert from customsiliconerings.com, while we provides the quality product, such as Oil Seal Viton Manufacturer , Slip Clutch Disc, Rubber Ring Seals,and more.
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