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Genes found for schizophrenia are involved in brain signaling

Date:
May 10, 2010
Source:
Children's Hospital of Philadelphia
Summary:
By analyzing the genomes of patients with schizophrenia, genetics researchers have discovered numerous copy number variations -- deletions or duplications of DNA sequences -- that increase the risk of developing schizophrenia. Significantly, many of these variations occur in genes that affect signaling among brain cells.

By analyzing the genomes of patients with schizophrenia, genetics researchers have discovered numerous copy number variations -- deletions or duplications of DNA sequences -- that increase the risk of developing schizophrenia. Significantly, many of these variations occur in genes that affect signaling among brain cells.

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"When we compared the genomes of patients with schizophrenia to those of healthy subjects, we found variations in genes that regulate brain functions, several of which are already known to be perturbed in patients with this disorder," said study leader Hakon Hakonarson, M.D., Ph.D., director of the Center for Applied Genomics at The Children's Hospital of Philadelphia. "Although much research remains to be done, detecting genes on specific pathways is a first step to identifying more specific targets for improved drug treatments."

The research appears in the Proceedings of the National Academy of Sciences.

A devastating psychiatric disorder that affects an estimated 1.5 percent of the population, or millions of Americans, schizophrenia may include hallucinations, disorganized speech, abnormal thought processes and other symptoms. It typically becomes apparent in late adolescence or early adulthood. Patients often have a family history of schizophrenia, and scientists believe the disorder results from an interaction of genetic predisposition and environmental effects.

Hakonarson and colleagues compared DNA samples from a total of 1,735 adult patients with schizophrenia to DNA from 3,485 healthy adult subjects, using highly automated genotyping tools. They used a whole-genome approach, covering the full set of genetic material from each individual, following their first analysis with a replication study.

The study team found copy number variations (CNVs) in or near genes that play important roles in the brain. Among those genes were CACNA1B and DOC2A, both of which carry the codes for proteins that use calcium signals to help control how neurotransmitters are released in the brain. Two other genes, RET and RIT2, are members of another signaling gene family known to be involved in brain development.

The researchers found that the genes and signaling systems linked to schizophrenia had some overlap with those for autism and for attention-deficit hyperactivity disorder. In fact, the current study found deletions in the same region of chromosome 16 as that found in a CNV study of autism spectrum disorders that Hakonarson led in 2009. "Although different brain regions may be affected in these different neuropsychiatric disorders, these overlaps suggest that there may be common features in their underlying pathogenesis," said Hakonarson. "These genes affect synaptic function, so deletions or duplications in those genes may alter how brain circuits are formed."

Hakonarson said future studies will investigate how these CNVs and other CNVs yet to be discovered may alter brain function. Ultimately, he added, better understanding of signaling pathways in the brain may enable researchers to devise better drugs for schizophrenia, drugs that can selectively act on those biological pathways, with better efficacy and fewer side effects for patients.

The National Institutes of Health provided funding support for this study, along with the Cotswold Foundation, and an Institutional Development Award to the Center for Applied Genomics from The Children's Hospital of Philadelphia. Hakonarson's co-authors were from The Children's Hospital of Philadelphia, the University of Pennsylvania School of Medicine; Mount Sinai School of Medicine; Sheba Medical Center, Tel Hashomer, Israel; and King's College, London, UK.


Story Source:

The above story is based on materials provided by Children's Hospital of Philadelphia. Note: Materials may be edited for content and length.


Journal Reference:

  1. Hakonarson et al. Strong synaptic transmission impact by copy number variations in schizophrenia. Proceedings of the National Academy of Sciences, 2010; DOI: 10.1073/pnas.1000274107

Cite This Page:

Children's Hospital of Philadelphia. "Genes found for schizophrenia are involved in brain signaling." ScienceDaily. ScienceDaily, 10 May 2010. <www.sciencedaily.com/releases/2010/05/100510151342.htm>.
Children's Hospital of Philadelphia. (2010, May 10). Genes found for schizophrenia are involved in brain signaling. ScienceDaily. Retrieved December 18, 2014 from www.sciencedaily.com/releases/2010/05/100510151342.htm
Children's Hospital of Philadelphia. "Genes found for schizophrenia are involved in brain signaling." ScienceDaily. www.sciencedaily.com/releases/2010/05/100510151342.htm (accessed December 18, 2014).

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