Schizophrenia is associated with somatic mutations occurring in utero


Date:
July 6, 2023
Source:
Cell Press
Summary:
As a psychiatric disorder with onset in adulthood, schizophrenia
is thought to be triggered by some combination of environmental
factors and genetics, although the exact cause is still not fully
understood.

Researchers have now found a correlation between schizophrenia and
somatic copy-number variants, a type of mutation that occurs early
in development but after genetic material is inherited. This study
is one of the first to rigorously describe the relationship between
somatic -- not inherited -- genetic mutations and schizophrenia
risk.


Facebook Twitter Pinterest LinkedIN Email

==========================================================================
FULL STORY ==========================================================================
As a psychiatric disorder with onset in adulthood, schizophrenia is
thought to be triggered by some combination of environmental factors and genetics, although the exact cause is still not fully understood. In a
study published in the journal Cell Genomics on July 6, researchers find
a correlation between schizophrenia and somatic copy-number variants,
a type of mutation that occurs early in development but after genetic
material is inherited. This study is one of the first to rigorously
describe the relationship between somatic -- not inherited -- genetic
mutations and schizophrenia risk.

"We originally thought of genetics as the study of inheritance. But now we
know that genetic mechanisms go way beyond that," says senior author Chris Walsh, an investigator at the Howard Hughes Medical Institute and chief
of genetics and genomics at Boston Children's Hospital. "We're looking
at mutations that are not inherited from the parents." The researchers analyzed genotype-marker data from over 20,000 blood samples of people
with or without schizophrenia from the Psychiatric Genomics Consortium.

They ultimately identified two genes -- NRXN1and ABCB11 -- that correlated
with schizophrenia cases when disruptedin utero. NRXN1, a gene that
helps transmit signals throughout the brain, has been associated with schizophrenia before.

However, this is the first study to associate somatic, not inherited,
NRXN1 mutations with schizophrenia.

Unlike inherited mutations, which are present in all the cells of the
body, somatic mutations are only present in a fraction of cells based
on when and where a mutation occurred. If a mutation occurs early in development, it is expected that the variant is present throughout the
body in a mosaic pattern.

On the basis of this principle, researchers can identify somatic mutations
that occurred early in development and are present not only in the brain
but also in a fraction of cells in the blood.

"If a mutation occurs after fertilization when there are only two cells,
the mutation will be present in half of the cells of the body," says
Walsh. "If it occurs in one of the first four cells, it will be present
in about a quarter of the cells of the body, and so on." The second
gene the researchers identified, ABCB11, is most known to encode a liver protein. "That one came out of nowhere for us," says Eduardo Maury, a
student in Harvard-MIT's MD-PhD program. "There have been some studies associating mutations in this gene with treatment-resistant schizophrenia,
but it hasn't been strongly implicated in schizophrenia per se." When the
team investigated further, they found that ABCB11is also expressed in
very specific subsets of neurons that carry dopamine from the brainstem
to the cerebral cortex. Most schizophrenia drugs are thought to act on
these cells to decrease an individual's dopamine levels, so this might
explain why the gene is associated with treatment resistance.

Next, the team is working towards identifying other acquired mutations
that might be associated with schizophrenia. Given that the study analyzed blood samples, it will be important to look at more brain-specific
mutations that might have been too subtle or recent in a patient's
life for this analysis to detect. In addition, somatic deletions or duplications might be an under- investigated risk factor associated with
other disorders.

"With this study, we show that it is possible to find somatic variants
in a psychiatric disorder that develops in adulthood," says Maury. "This
opens up questions about what other disorders might be regulated by
these kinds of mutations."
* RELATED_TOPICS
o Health_&_Medicine
# Mental_Health_Research # Birth_Defects # Brain_Tumor
# Genes
o Mind_&_Brain
# Schizophrenia # Disorders_and_Syndromes # Mental_Health
# Psychiatry
* RELATED_TERMS
o Schizophrenia o Dopamine_hypothesis_of_schizophrenia o
Psychiatric_service_dog o Alzheimer's_disease o Mental_illness
o Hip_dysplasia o Mutation o Molecular_biology

==========================================================================

Print

Email

Share ========================================================================== ****** 1 ****** ***** 2 ***** **** 3 ****
*** 4 *** ** 5 ** Breaking this hour ==========================================================================
* First_Snapshots_of_Fermion_Pairs *
Why_No_Kangaroos_in_Bali;_No_Tigers_in_Australia
* New_Route_for_Treating_Cancer:_Chromosomes *
Giant_Stone_Artefacts_Found:_Prehistoric_Tools
* Astonishing_Secrets_of_Tunicate_Origins *
Most_Distant_Active_Supermassive_Black_Hole *
Creative_People_Enjoy_Idle_Time_More_Than_Others
* Restoring_Fragile_X_Protein_Production *
Earth's_Solid_Metal_Sphere_Is_'Textured' *
Elephants_Vary_Their_Dinner_Menu_Day-To-Day

Trending Topics this week ========================================================================== HEALTH_&_MEDICINE Patient_Education_and_Counseling Birth_Defects
Cholesterol MIND_&_BRAIN Educational_Psychology Stroke Autism
LIVING_&_WELL Fitness Healthy_Aging Nutrition


==========================================================================

Strange & Offbeat ========================================================================== HEALTH_&_MEDICINE Holograms_for_Life:_Improving_IVF_Success Grocery_Store_Carts_Set_to_Help_Diagnose_Common_Heart_Rhythm_Disorder_and Prevent_Stroke DNA_Can_Fold_Into_Complex_Shapes_to_Execute_New_Functions MIND_&_BRAIN AI_Tests_Into_Top_1%_for_Original_Creative_Thinking Everyone's_Brain_Has_a_Pain_Fingerprint_--_New_Research_Has_Revealed_for_the First_Time Scientists_Discover_Spiral-Shaped_Signals_That_Organize_Brain_Activity LIVING_&_WELL Illusions_Are_in_the_Eye,_Not_the_Mind Amputees_Feel_Warmth_in_Their_Missing_Hand Why_Do_Champagne_Bubbles_Rise_the_Way_They_Do?_Scientists'_New_Discovery_Is Worthy_of_a_Toast Story Source: Materials provided by Cell_Press. Note:
Content may be edited for style and length.


========================================================================== Journal Reference:
1. Eduardo A. Maury et al. Schizophrenia-associated somatic copy-number
variants from 12,834 cases reveal recurrent NRXN1 and ABCB11
disruptions.

Cell Genomics, 2023; 100356 DOI: 10.1016/j.xgen.2023.100356 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2023/07/230706124520.htm

--- up 1 year, 18 weeks, 3 days, 10 hours, 50 minutes
* Origin: -=> Castle Rock BBS <=- Now Husky HPT Powered! (1:317/3)