Novel chromosome abnormality appears to increase risk of autism

“While epidemiologic studies indicate a very large genetic component to autism, little is known about how specific genes are involved,” says Mark Daly, PhD, of MGH Center for Human Genetic Research, the study’s senior author for gene discovery. “We’re still a long way from understanding how this chromosomal deletion or duplication increases the risk for autism, but this is a critical first step toward that knowledge.”

Population studies indicate that up to 90 percent of cases of autism and what are referred to as autism spectrum disorders have some genetic component, but only 10 percent of cases can be attributed to known genetic and chromosomal syndromes. Since several of those conditions involve deletions or duplications of chromosomal segments – including an inherited deletion of a region of chromosome 15 – the investigators conducted a complete genome scan of samples from the Autism Genome Research Exchange, which contains DNA from families in which at least one child has autism or a related disorder.

The scan of more than 1,400 affected individuals and a similar number of their unaffected parents revealed that an identical region of chromosome 16 was deleted in 5 individuals with an autism spectrum disorder but not in any of the parents, implying that the deletion had occurred spontaneously and was not inherited. To confirm this observation, clinical testing data from almost 1,000 patients from Children’s Hospital Boston – about half of whom had been diagnosed with autism or a related developmental delay – was evaluated. Among those with a developmental disorder, 5 children had the same deletion, and in another 4 the chromosome segment was duplicated. Again, no abnormalities were seen in DNA from children without autism or developmental delay.

Confirmatory data was also obtained by colleagues from deCODE Genetics of Iceland, who found the same deletion in 3 of almost 300 individuals with an autism spectrum disorder and also in a few with other psychiatric or language disorders. Among almost 20,000 members of the deCODE database who had not been evaluated for language or psychiatric disorders, the deletion was seen in only 2 individuals. Results from the deCODE scan indicate that, while this chromosomal deletion occurs in only .01 percent of the general population, it is 100 times more prevalent in those with autism spectrum disorders.

“These large, non-inherited chromosomal deletions are extremely rare,” says Daly, “so finding precisely the same deletion in such a significant proportion of patients suggests that it is a very strong risk factor for autism. We’re now pursuing more detailed genetic studies to figure out which genes in this region are responsible for this effect in order to gain a better understanding of the underlying biology and potential clues to therapeutic approaches.”

A member of the Autism Consortium, which includes 14 Boston-area institutions, Daly adds, “The ability to rapidly and seamlessly translate research findings to the evaluation of patients under clinical care – providing families with information that can help them understand their child’s condition and assess potential risks to other children – relied on the integrated community of researchers and clinicians made possible through the Autism Consortium.” Daly is an assistant professor of Medicine at Harvard Medical School and a member of the Broad Institute of Harvard and Massachusetts Institute of Technology.

Source: Massachusetts General Hospital

Aberrations in region of chromosome 1q21.1 associated with broad range of disorders in children
Researchers have discovered a submicroscopic aberration in a particular region of human chromosome 1q21.1 that appears to be associated with a variety of developmental disorders in children. The aberration can manifest itself as unexplained mild or moderate mental retardation, growth retardation, learning disabilities, seizures, autism, heart defects, other congenital abnormalities, cataracts, small head size, unusual facial features, hand deformities, or skeletal problems. Some people who have the aberration are only slightly affected or apparently unaffected, others are more seriously impaired.
The first autism disease genes
The autistic disorder was first described, more than sixty years ago, by Dr. Leo Kanner of the Johns Hopkins Hospital (USA), who created the new label 'early infantile autism'. At the same time an Austrian scientist, Dr. Hans Asperger, described a milder form of the disorder that became known as Asperger Syndrome, characterised by higher cognitive abilities and more normal language function. Today, both disorders are classified in the continuum of 'Pervasive Developmental Disorders' (PDD), more often referred to as Autism Spectrum Disorders (ASD).
Middle Eastern families yield intriguing clues to autism
Research involving large Middle Eastern families, sophisticated genetic analysis and groundbreaking neuroscience has implicated a half-dozen new genes in autism. More importantly, it strongly supports the emerging idea that autism stems from disruptions in the brain's ability to form new connections in response to experience – consistent with autism's onset during the first year of life, when many of these connections are normally made.
Researchers Pinpoint Gene Mutations Responsible for 10 Percent of Schizophrenia
Scans of the genome of patients with schizophrenia have revealed rare spontaneous copy number mutations that account for at least 10 percent of the non-familial cases of the disease. Researchers describe specific genetic mutations present in individuals who have schizophrenia, but not present in their biological parents who do not have the disease.
8 new human genome projects offer large-scale picture of genetic difference
A nationwide consortium led by the University of Washington in Seattle has completed the first sequence-based map of structural variations in the human genome, giving scientists an overall picture of the large-scale differences in DNA between individuals. The project gives researchers a guide for further research into these structural differences, which are believed to play an important role in human health and disease. The results appear in the May 1 issue of the journal Nature.
Sticky blood protein yields clues to autism
Many children with autism have elevated blood levels of serotonin – a chemical with strong links to mood and anxiety. But what relevance this “hyperserotonemia” has for autism has remained a mystery.
Recurrent genetic deletion linked to autism
Loss of a small portion of chromosome 16, known as 16p11.2, is significantly associated with autism report researchers from the University of Chicago Medical Center, the University of Illinois at Chicago, and the Roswell Park Cancer Institute in an article, published Dec. 21, 2007, online by the journal Human Molecular Genetics.
Researchers learn more about genetic mutation linked to autism
University of Iowa researchers have learned more about a genetic mutation that contributes to autism. The mutation occurred in sperm cells of a father, who does not have autism, but passed the condition on to two of his children.

Novel chromosome abnormality appears to increase risk of autism

Related stories:

News discussion: