Biomarkers

Link Between Genetic Defect And Brain Changes In Schizophrenia Demonstrated

Source: 
Science Daily
Date Published: 
October 17, 2009
Abstract: 

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

Utah Researchers Discover Another Genetic Link to Autism

Source: 
Salt Lake Tribune
Date Published: 
October 8, 2009
Abstract: 

An international consortium of researchers, including three from the University of Utah, has discovered yet another genetic link to autism. Studying the genes of more than 1,000 families -- including 150 from Utah -- who have more than one person with the disorder, the researchers found a region on chromosome 5 that is strongly associated with autism.

Genome Wide Study of Autism Published in Nature

Source: 
EurekAlert
Date Published: 
October 7, 2009
Abstract: 

In one of the first studies of its kind, an international team of researchers has uncovered a single-letter change in the genetic code that is associated with autism. The finding, published in the October 8 issue of the journal Nature, implicates a neuronal gene not previously tied to the disorder and more broadly, underscores a role for common DNA variation. In addition, the new research highlights two other regions of the genome, which are likely to contain rare genetic differences that may also influence autism risk.

California Dept of Health Publishes Study on Autism and Maternal/Paternal Age

Source: 
American Journal of Epidemiology
Date Published: 
October 5, 2009
Abstract: 

Reviewing a larger population than in any other study of its kind, the California Department of Public Health (CDPH) has found that as parents age their risk of giving birth to a child with autism increases modestly. Published in the American Journal of Epidemiology, the new CDPH study shows that for each 10-year increase in a mother’s age, the risk of autism increased by about 38 percent. For each 10-year increase in a father’s age, the risk of autism increased by about 22 percent.

Genome-Wide Analyses of Exonic Copy Number Variants in a Family-Based Study Point to Novel Autism Susceptibility Genes

Source: 
PLOS Genetics, Bucan M, Abrahams BS, Wang K, Glessner JT, Herman EI, et al.
Date Published: 
June 2009
Year Published: 
2009

The study identified 27 different genetic regions where rare copy number variations - missing or extra copies of DNA segments - were found in the genes of children with autism spectrum disorders, but not in the healthy controls. The researchers, including geneticists from the University of Pennsylvania School of Medicine and The Children's Hospital of Philadelphia (CHOP) compared genetic samples of 3,832 individuals from 912 families with multiple autistic children against genetic samples of 1,070 disease-free children. Besides the identification of 27 regions harboring rare variants in children with ASDs, the study also uncovered two novel genes where variations were found, BZRAP1 and MDGA2 - thought to be important in synaptic function and neurological development, respectively. Interestingly, key variants on these genes were passed down in some, but not all, of the affected individuals in families.

High-density SNP association study of the 17q21 chromosomal region linked to autism identifies CACNA1G as a novel candidate gene

Source: 
Molecular Psychiatry, Strom, Stone, Bosch, Merriman, Cantor, Geschwind, and Nelson
Date Published: 
May 2009
Year Published: 
2009

(From a UCLA press release) UCLA scientists have discovered a variant of a gene called CACNA1G that may increase a child's risk of developing autism, particularly in boys. "We found that a common form of the gene occurs more frequently in the DNA of families that have two or more sons affected by autism, but no affected daughters," explained Dr. Stanley Nelson, professor of human genetics at the David Geffen School of Medicine at UCLA. The researchers traced the genetic markers to CACNA1G, which helps move calcium between the cells. They discovered that the gene has a common variant that appears in the DNA of nearly 40 percent of the population. "This alternate form of CACNA1G consistently increased the correlation to autism spectrum disorder, suggesting that inheriting the gene may heighten a child's risk of developing autism," observed Nelson. How the gene contributes to higher autism risk remains unclear, but Nelson emphasized that it cannot be considered a risk factor on its own. "This variant is a single piece of the puzzle," he said. "We need a larger sample size to identify all of the genes involved in autism and to solve the whole puzzle of this disease." The UCLA team's next step will be to sequence the gene in people who possess the altered variant in order to identify the exact change that increases autism risk. These subtle variations offer potential markers for the real mutation causing greater susceptibility to the disease.

Newly Found Genetic Variation Linked to Autism

Source: 
Nature
Date Published: 
April 2009
Year Published: 
2009

A newly identified genetic variant could account for up to 15 percent of autism cases, say researchers who studied genes that are important in connecting brain cells.  Researchers say the variant is carried by about 65 per cent of people with autism.
 

Two-year-olds with autism orient to non-social contingencies rather than biological motion

Source: 
Nature, Klin, Lin, Gorrindo, Ramsay, Jones
Date Published: 
March 2009
Year Published: 
2009

Typically developing human infants preferentially attend to biological motion within the first days of life. This ability is highly conserved across species and is believed to be critical for filial attachment and for detection of predators. The neural underpinnings of biological motion perception are overlapping with brain regions involved in perception of basic social signals such as facial expression and gaze direction, and preferential attention to biological motion is seen as a precursor to the capacity for attributing intentions to others. However, in a serendipitous observation, we recently found that an infant with autism failed to recognize point-light displays of biological motion, but was instead highly sensitive to the presence of a non-social, physical contingency that occurred within the stimuli by chance. This observation raised the possibility that perception of biological motion may be altered in children with autism from a very early age, with cascading consequences for both social development and the lifelong impairments in social interaction that are a hallmark of autism spectrum disorders. Here we show that two-year-olds with autism fail to orient towards point-light displays of biological motion, and their viewing behavior when watching these point-light displays can be explained instead as a response to non-social, physical contingencies—physical continimplications for understanding the altered neurodevelopmental trajectory of brain specialization in autism.

Recurrent 16p11.2 Microdeletions in Autism

Source: 
Human Molecular Genetics, Kumar, KaraMohamed, et al
Date Published: 
2008
Year Published: 
2008

Autism is a childhood neurodevelopmental disorder with a strong genetic component, yet the identification of autism susceptibility loci remains elusive. We investigated 180 autism probands and 372 control subjects by array comparative genomic hybridization (aCGH) using a 19K whole-genome tiling path bacterial artificial chromosome microarray to identify submicroscopic chromosomal rearrangements specific to autism. We discovered a recurrent 16p11.2 microdeletion in two probands with autism and none in controls. The deletion spans approximately 500-kb and is flanked by approximately 147-kb segmental duplications (SDs) that are >99% identical, a common characteristic of genomic disorders. We assessed the frequency of this new autism genomic disorder by screening an additional 532 probands and 465 controls by quantitative PCR and identified two more patients but no controls with the microdeletion, indicating a combined frequency of 0.6% (4/712 autism versus 0/837 controls; Fisher exact test P = 0.044). We confirmed all 16p11.2 deletions using fluorescence in situ hybridization, microsatellite analyses and aCGH, and mapped the approximate deletion breakpoints to the edges of the flanking SDs using a custom-designed high-density oligonucleotide microarray. Bioinformatic analysis localized 12 of the 25 genes within the microdeletion to nodes in one interaction network. We performed phenotype analyses and found no striking features that distinguish patients with the 16p11.2 microdeletion as a distinct autism subtype. Our work reports the first frequency, breakpoint, bioinformatic and phenotypic analyses of a de novo 16p11.2 microdeletion that represents one of the most common recurrent genomic disorders associated with autism to date.

Identifying autism Loci and Genes by Tracing Recent Shared Ancestry

Source: 
Science, Morrow, Yoo, et al
Date Published: 
2008

To find inherited causes of autism-spectrum disorders, we studied families in which parents share ancestors, enhancing the role of inherited factors. We mapped several loci, some containing large, inherited, homozygous deletions that are likely mutations. The largest deletions implicated genes, including PCDH10 (protocadherin 10) and DIA1 (deleted in autism1, or c3orf58), whose level of expression changes in response to neuronal activity, a marker of genes involved in synaptic changes that underlie learning. A subset of genes, including NHE9 (Na+/H+ exchanger 9), showed additional potential mutations in patients with unrelated parents. Our findings highlight the utility of "homozygosity mapping" in heterogeneous disorders like autism but also suggest that defective regulation of gene expression after neural activity may be a mechanism common to seemingly diverse autism mutations.