Despite advances in genomics in recent years, schizophrenia remains one of the most complex challenges of both genetics and neuroscience. The chromosomal abnormality 22q11 deletion syndrome, also known as DiGeorge syndrome, offers a way in, since it is one of the strongest genetic risk factors for schizophrenia.
Out of dozens of genes within the 22q11 deletion, several encode proteins found in mitochondria. A team of Emory scientists, led by cell biologist Victor Faundez, recently analyzed Read more
A recent issue of Emory Health magazine had an article describing the progress of clinical trials for fragile X syndrome, the most common inherited cause of intellectual disability. The article included interviews with the parents of a boy, Samuel McKinnon, who is participating in one of the phase III clinical trials here at Emory.
Last week, results for the phase II study for the same medication were published in Science Translational Medicine. The drug, called STX209 or arbaclofen, is one of the first designed to treat the molecular changes in the brain caused by fragile X syndrome. STX209 shows some promise in its ability to reduce social withdrawal, a key symptom of fragile X syndrome.
In one case, a boy was able to attend his birthday party for the first time in his life. In the past, he had been too shy and couldn’t tolerate hearing people sing Happy Birthday to You, the studyâ€™s lead author Elizabeth Berry-Kravis, MD, PhD from Rush University, told USA Today.
These results have generated excitement among autism researchers and specialists, because a fraction of individuals with fragile X mutations have autism and the same drug strategy may be able to address deficits in other forms of autism.
1. Autism and fragile X are not the same thing.
2. This was a phase II study, the phase III results are yet to come.
3. The study authors are up front about saying that the â€œprimary endpointâ€ (irritability) showed no difference between drug and placebo.
A team led by Emory genetics chair Steve Warren identified the gene responsible for fragile X in 1991, and Emory scientists have been important players in figuring out its effects on the brain.
Warren and colleague Mika Kinoshita are co-authors on a companion paper in STM on treatment of fragile X mice. A thoughtful review piece in the same issue of STM lays out current issues in developing therapies for â€œchildhood disorders of the synapse.â€
Geneticist Madhuri Hegde and her colleagues have a paper in the journal Genome Researchthat addresses the question: where do copy number variations come from?
Madhuri Hegde, PhD
Copy number variations (CNVs), which are deletions or duplications of small parts of the genome, have been the subject of genetic research for a long time. But only in the last few years has it become clear that copy number variations are where the action is for complex diseases such as autism and schizophrenia. Geneticists studying these diseases are shifting their focus from short, common mutations (often, single nucleotide polymorphisms or SNPs) to looking at rarer variants such as CNVs. A 2009 discussion of this trend with Steve Warren and Brad Pearce can be found here.
Hegde is the Scientific Director of the Department of Human Geneticsâ€™ clinical laboratory. Postdoctoral fellow Arun Ankala is the first author. In the new paper, Ankala and Hegde examine rearrangements in patientsâ€™ genomes that arose in 62 clinical cases of Duchenneâ€™s muscular dystrophy and several other diseases. Mutations in the DMD gene are responsible for Duchenneâ€™s muscular dystrophy.
The pattern of the rearrangement hints what events took place in the cell beforehand, and hint that a problem took place during replication of the DNA. The signature is a tandem duplication of a short segment next to a large deletion, indicating how the DNA was repaired.
The authors note that the DMD locus is especially prone to these types of problems because it is much larger than other gene loci. The gene is actually the longest human gene known on the DNA level, covering 2.4 megabases (0.08 percent of the genome.)
Replication origins are where the DNA copying machinery in the cell starts unwinding and copying the DNA.Â Bacterial circular chromosomes have just one replication origin. In contrast, humans have thousands of replication origins spread across our chromosomes. In the discussion, the authors suggest that DNA copying problems may also explain duplications and historically embedded rearrangements of the genome.
Emory genetic researchers Daniel Moreno De Luca, Christa Lese Martin and David Ledbetter were part of a team that produced a landmark result in autism genetics. The team identified hundreds of regions of the genome where spontaneous mutations are implicated in autism.Â Spontaneous mutations are those that arise for the first time in an individual, rather than being inherited from parents.
Christa Lese Martin, PhD
The team was led by Matthew State at Yale, and their results were published in the journal Neuron. Moreno De Luca discussed the topic in Spanish on a recent edition of the NPR program Science Friday. The June 10 segment was focused onÂ autism genetics.
The teamÂ made an intriguing finding on a segment of chromosome 7. Deletion of the region is associated with Williams syndrome, where individuals can exhibit “striking verbal abilities, highly social personalities and an affinity for music.” Duplication of the same region, they found, is associated with autism.
Daniel Moreno De Luca, MD MSc
Companion studies also shed light on the question of why boys are more likely to develop autism than girls, and begin to outline a network of genes whose activity is altered in the brains of individuals with autism.
Researchers at Emory University and the University of Georgia have received funding from the National Institutes of Health to study the neurobiological mechanisms for how regular aerobic exercise may prevent drug abuse relapse. The grant is for $1.9 million over the next five years.
â€œThis research will provide new insight into how regular exercise may attenuate drug abuse in humans,â€ Weinshenker says â€œMore importantly, it may reveal a neural mechanism through which exercise may prevent the relapse into drug-seeking behavior.â€
During the study, Weinshenker and UGA co-investigator Philip Holmes, professor of psychology in the Franklin College of Arts and Sciences, will measure exercise-induced increases of the galanin gene activity in the rat brain.