First Sequencing for the Full Genome of Autism

The first full genome sequencing for autism has been completed which provides immense promise regarding autism prevention, diagnosis, and treatment.

A collaborative formed by Autism Speaks, the world's leading autism science and advocacy organization, has found full genome sequencing examining the entire DNA code of individuals with autism spectrum disorder (ASD) and their family members to provide the definitive look at the wide ranging genetic variations associated with ASD. The study published online today in American Journal of Human Genetics, reports on full genome sequencing on 32 unrelated Canadian individuals with autism and their families, participants in the Autism Speaks Autism Genetic Resource Exchange (AGRE). The results include both inherited as well as spontaneous or de novo, genetic alterations found in one half of the affected families sequenced.

This dramatic finding of genetic risk variants associated with clinical manifestation of ASD or accompanying symptoms in 50 percent of the participants tested is promising, as current diagnostic technology has only been able to determine a genetic basis in about 20 percent of individuals with ASD tested. The large proportion of families identified with genetic alterations of concern is in part due to the comprehensive and uniform ability to examine regions of the genome possible with whole genome sequencing missed in other lower resolution genome scanning approaches.

"From diagnosis to treatment to prevention, whole genome sequencing efforts like these hold the potential to fundamentally transform the future of medical care for people with autism," stated Autism Speaks Chief Science Officer and study co-author Robert Ring, Ph.D.

The study identified genetic variations associated with risk for ASD including de novo, X-linked and other inherited DNA lesions in four genes not previously recognized for ASD; nine genes previously determined to be associated with ASD risk; and eight candidate ASD risk genes. Some families had a combination of genes involved. In addition, risk alterations were found in genes associated with fragile X or related syndromes (CAPRIN1 and AFF2), social-cognitive deficits (VIP), epilepsy (SCN2A and KCNQ2) as well as NRXN1 and CHD7, which causes ASD-associated CHARGE syndrome.

"Whole genome sequencing offers the ultimate tool to advance the understanding of the genetic architecture of autism," added lead author Dr. Stephen Scherer, senior scientist and director of the Centre for Applied Genomics at The Hospital for Sick Children (SickKids) and director of the McLaughlin Centre at the University of Toronto. "In the future, results from whole genome sequencing could highlight potential molecular targets for pharmacological intervention, and pave the way for individualized therapy in autism. It will also allow for earlier diagnosis of some forms of autism, particularly among siblings of children with autism where recurrence is approximately 18 per cent."

This $1 million collaboration of Autism Speaks, SickKids, BGI and Duke University piloted Autism Speaks' initiative to generate the world's largest library of sequenced genomes of individuals with ASD announced in late 2011. "As we continue to test more individuals and their family members from the AGRE cohort, we expect to discover and study additional genetic variants associated with autism. This collaboration will accelerate basic and translational research in autism and related developmental disabilities," concluded Autism Speaks Vice President for Scientific Affairs Andy Shih, Ph.D. who oversees the collaboration, "and this collection of sequenced genomes will facilitate new collaborations engaging researchers around the world, and enable public and private entities to pursue pivotal research."

In this pilot effort, a total of 99 individuals were tested, including the 32 individuals with ASD (25 males and seven females) and their two parents, as well as three members of one control family not on the autism spectrum. Using families in the Autism Speaks AGRE collection, this Autism Speaks initiative will ultimately perform whole genome sequencing on more than 2,000 participating families who have two or more children on the autism spectrum. The data from the 10,000 AGRE participants will enable new research in the genomics of ASD, and significantly enhance the science and technology networks of Autism Speaks and its collaborators.

Read more here

New technologies utilized for epilepsy treatment

This article claims that developing new technologies is the best way to treat epilepsy. It also goes over a few of the technologies currently utilized for epilepsy treatment.

Speaking in the lead up to Purple Day for Epilepsy Awareness (Tuesday 26 March), geneticist Professor Jozef Gecz says advances in DNA sequencing have been a huge leap forward in understanding epilepsy. 

This, combined with the use of stem cells in laboratory research, will lead to further advances in epilepsy treatment, he says. 

However, he cautions that the same technology has also helped to reveal that epilepsy is a far more complex condition than previously thought. 

"Scientists used to believe that epilepsy was just one condition, possibly with one main cause. But now we know it is a very complex series of neurological disorders – it is many epilepsies, instead of just one epilepsy, with multiple causes and various symptoms," says Professor Gecz, from the University of Adelaide's School of Paediatrics and Reproductive Health. 

Epilepsy is common, with up to 3% of the Australian population experiencing epilepsy at some stage in their lives. Genetic and environmental factors, and trauma, can all play a role in the development of epilepsy. Most (but not all) forms cause sufferers to experience seizures, which vary in severity. 

Research in Adelaide has played an important role in the understanding of epilepsy in recent years. 

"It's really thanks to the pioneering work of Dr John Mulley (Women's and Children's Hospital and University of Adelaide), who discovered the first gene for idiopathic epilepsy almost 20 years ago. Since then, almost 40 idiopathic epilepsy genes have been discovered, many of them by researchers here in Adelaide," Professor Gecz says. 

"There are more than 300 genes known today in which DNA mutations can give rise to some form of epilepsy, in addition to other problems like intellectual disability, autism or psychiatric problems. 

"Thanks to genetic sequencing technology, in most cases we are now able to solve the mystery about what kind of epilepsy a patient has, and we can do this very quickly, very accurately, and cost effectively. 

"Molecular diagnosis is making a huge impact on treatment – it's really taken off in the last few years, and it has the potential to be even more effectively used in the future. Clinicians can now be guided by genetic information when considering treatment of patients with specific epilepsies." 

Professor Gecz and colleagues are currently involved in a major national study of epilepsy, with his lab focusing on the "genetic architecture" of the condition.

Read more here