Using DNA to predict schizophrenia and autism

August 31, 2017, Osaka University
A statistically significant association between the variant Ala55Thr in CX3CR1 with SCZ and ASD phenotypes. Credit: Osaka University

Huntington's disease, cystic fibrosis, and muscular dystrophy are all diseases that can be traced to a single mutation. Diagnosis in asymptomatic patients for these diseases is relatively easy—you have the mutation? Then you are at risk. Complex diseases, on the other hand, do not have a clear mutational footprint. A new multi-institutional study by Japanese researchers shows a potential rare gene mutation that could act as a predictor for two neurodevelopmental disorders, schizophrenia and autism.

"Aberrant synapse formation is important in the pathogenesis of and autism," says Osaka University Professor Toshihide Yamashita, one of the authors of the study. "Microglia contribute to the structure and function of synapse connectivities."

Microglia are the only cells in the brain that express the receptor CX3CR1. Mutations in this receptor are known to affect synapse connectivity and cause abnormal social behavior in mice. They have also been associated with neuroinflammatory diseases such as multiple sclerosis, but no study has shown a role in neurodevelopment disorders.

Working with this hypothesis, the researchers conducted a statistical analysis of the CX3CR1 gene in over 7000 schizophrenia and autism patients and healthy subjects, finding one mutant candidate, a single amino acid switch from alanine to threonine, as a candidate marker for prediction.

"Rare variants alter gene function but occur at low frequency in a population. They are of high interest for the study of complex diseases that have no clear mutational cause," said Yamashita, who added the alanine threonine substitution was a rare variant.

Illustration. Credit: Osaka University

The structure of CX3CR1 includes a domain known as Helix 8, which is important for initiating a signaling cascade. Computer models showed that one amino acid change is enough to compromise the signaling.

"The variant changes the region from hydrophobic to hydrophilic and destabilize Helix 8. We overexpressed the mutation in cells and found Akt signaling was disrupted," explains Yamashita.

According to Yamashita, the findings are the first to connect a genetic variation in microglia with . Moreover, he hopes that the discovery could become a basis for predictive diagnostics.

"There is no reliable way to diagnose schizophrenia or autism in . Deeper understanding of the will help us develop preventative measures."

Explore further: Genetic analysis finds rare, damaging variants contribute to the risk of schizophrenia

More information: K Ishizuka et al, Rare genetic variants in CX3CR1 and their contribution to the increased risk of schizophrenia and autism spectrum disorders, Translational Psychiatry (2017). DOI: 10.1038/tp.2017.173

Related Stories

Genetic analysis finds rare, damaging variants contribute to the risk of schizophrenia

June 27, 2017
(Medical Xpress)—Via genetic analysis, a large international team of researchers has found rare, damaging gene variants that they believe contribute to the risk of a person developing schizophrenia. In their paper published ...

Stabilizing TREM2 – a potential strategy to combat Alzheimer's disease

August 30, 2017
A gene called triggering receptor expressed on myeloid cells 2, or TREM2, has been associated with numerous neurodegenerative diseases, such as Alzheimer's disease, Frontotemporal lobar degeneration, Parkinson's disease, ...

Active non-coding DNA might help pinpoint genetic risk for psychiatric disorders

August 16, 2017
Northwestern Medicine scientists have demonstrated a new method of analyzing non-coding regions of DNA in neurons, which may help to pinpoint which genetic variants are most important to the development of schizophrenia and ...

Drugs that alter inhibitory targets offer therapeutic strategies for autism, schizophrenia

February 21, 2017
Memories are formed at structures in the brain known as dendritic spines, which communicate with other brain cells through "synapses." The number of these brain connections decreases by half after puberty in a process termed ...

'Overlooked and misunderstood' gene linked to schizophrenia

October 4, 2016
Scientists have discovered new evidence strengthening the link between a previously misunderstood gene and major mental illnesses such as schizophrenia, bipolar disorder, depression and autism.

Defect in non-coding DNA might trigger brain disorders such as severe language impairment

March 14, 2017
Genetic variation in the non-coding DNA could give rise to language impairments in children and other neurodevelopmental disorders including schizophrenia, autism, and bipolar disorder, scientists from the Max Planck Institute ...

Recommended for you

Beef jerky and other processed meats associated with manic episodes

July 18, 2018
An analysis of more than 1,000 people with and without psychiatric disorders has shown that nitrates—chemicals used to cure meats such as beef jerky, salami, hot dogs and other processed meat snacks—may contribute to ...

Forty percent of people have a fictional first memory, says study

July 17, 2018
Researchers have conducted one of the largest surveys of people's first memories, finding that nearly 40 per cent of people had a first memory which is fictional.

Celebrating positives improves classroom behavior and mental health

July 17, 2018
Training teachers to focus their attention on positive conduct and to avoid jumping to correct minor disruption improves child behaviour, concentration and mental health.

Protein found to be key component in irregularly excited brain cells

July 17, 2018
In a new study in mice, researchers have identified a key protein involved in the irregular brain cell activity seen in autism spectrum disorders and epilepsy. The protein, p53, is well-known in cancer biology as a tumor ...

Algorithm identifies patients best suited for antidepressants

July 17, 2018
McLean Hospital researchers have completed a study that sought to determine which individuals with depression are best suited for antidepressant medications. Their findings, published in Psychological Medicine on July 2, ...

World's largest study on allergic rhinitis reveals new risk genes

July 17, 2018
An international team of scientists led by Helmholtz Zentrum München and University of Copenhagen has presented the largest study so far on allergic rhinitis in the journal Nature Genetics. The data of nearly 900,000 participants ...

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

dnatwork
not rated yet Aug 31, 2017
If it changes the region from hydrophobic to hydrophilic, you don't just have a diagnostic target; that's a treatment target. Find something that switches it back despite the mutation, and the effects should be mitigated.

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.