Abnormalities in a Highly Duplicated Genome Region May Reveal Continuities in Symptoms of Schizophrenia and Autism

Abnormalities in a Highly Duplicated Genome Region May Reveal Continuities in Symptoms of Schizophrenia and Autism

Posted: March 7, 2016

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Schizophrenia and autism may be related disorders that, at least in part, share similar genetic roots, new research suggests. Indeed, say the scientists, rather than distinct and independent disorders, various subtypes of each may represent different manifestations of changes in the same gene family, with varying symptoms creating a broad continuum of symptoms.

In a study published online December 15, 2015 in Translational Psychiatry, the researchers observed how a region of DNA previously associated with autism is also altered in patients with schizophrenia. The research team from the University of Colorado was led by James Sikela, Ph.D., and lead author Veronica Searles Quick, Ph.D.; it also included Ann Olincy, M.D., a 1997 and 2002 NARSAD Young Investigator grantee.

Scientists over the years have proposed a wide range of theories about the connection between autism and schizophrenia. Looking at the symptoms selectively, it is possible to find support for many hypotheses.

Schizophrenia & autism may be related disorders that partly share genetic roots, new research suggests. Tweet >

Schizophrenia symptoms broadly fall into two classes. So-called positive symptoms are those that manifest as hallucinations or delusions, for example. In contrast, negative symptoms are characteristics that patients lose, like diminished cognitive and social capabilities. Positive symptoms in schizophrenia are unlike any features of autism, while negative symptoms mirror some features of autism, like deficits in communication and social behavior.

The new work proposes that both autism and schizophrenia may arise from common genetic origins. Indeed, other studies have found that duplications within a specific genomic region are linked with one disorder while deletions of the same region are linked with the other, suggesting that the diseases involve “copy number” changes (dosage changes) of the same DNA sequences. The researchers looked at changes in one gene family that is composed of hundreds of copies of a protein domain known as DUF1220, which has been previously associated with both autism and human brain evolution. The number of copies of DUF1220 can vary greatly from one individual with autism to the next but increase as severity increases.

The researchers measured the number of copies of DUF1220 (subtype CON1) in schizophrenia patients with positive and negative symptoms. They found that negative symptoms correlated with extra copies of DUF1220. Extra copies are also seen in autism patients. In contrast, patients with positive symptoms had fewer than normal copies of DUF1220.  The team also found that as the severity of positive symptoms increased, DUF1220 copy number decreased, a finding that is the opposite of what was found with autism severity.

The work suggests that specific symptoms of autism and schizophrenia may be shared as a result of abnormal copy numbers of DNA sequences from the same gene family.  In some individuals, in other words, mutations in one critical area of the genome might account for aspects of both illnesses, in at least some patients. “Specifically,” says Dr. Sikela, “variation in DUF1220 copy number contributes in a dose-dependent manner -- to schizophrenia disease risk and to the severity of both disorders.  

This research, he stressed, is only a preliminary inquiry into the ways in which these two disorders, and indeed other psychiatric illnesses, may share symptoms as a result of anomalies within the same gene family.

Takeaway: Mutations in one critical genome area may account for aspects of both schizophrenia and autism, in some patients. A study revealed that the number of copies of a variant of the DUF1220 gene contributes to schizophrenia disease risk and to the severity of both disorders.