Related Experiment Video

Updated: Sep 8, 2026

A Strategy to Identify de Novo Mutations in Common Disorders such as Autism and Schizophrenia
05:51

A Strategy to Identify de Novo Mutations in Common Disorders such as Autism and Schizophrenia

Published on: June 15, 2011

Alteration of branch site consensus sequence and enhanced pre-mRNA splicing of an NMDAR1 intron not associated with

Linda Hammond1, Daniela Castanotto, Sharmon R Rice

  • 1Division of Molecular Medicine, City of Hope National Medical Center, Duarte, California 91010-0269, USA.

American Journal of Medical Genetics
|September 5, 2002
PubMed

Insights

A genetic variant in the N-methyl-D-aspartate receptor 1 (NMDAR1) gene, initially suspected to disrupt splicing in schizophrenia, actually enhanced splicing efficiency. This finding suggests the variant is not a cause of schizophrenia in the studied population.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genetics

Background:

  • Aberrant pre-mRNA splicing contributes to genetic diseases.
  • The N-methyl-D-aspartate receptor 1 (NMDAR1) gene has eight known splice variants.
  • NMDAR1 was investigated as a candidate gene for schizophrenia.

Purpose of the Study:

  • To investigate a microdeletion/insertion (del/ins) in NMDAR1 intron 10 in an African-American male with schizophrenia.
  • To determine the effect of the del/ins variant on NMDAR1 splicing efficiency.
  • To assess the association and cosegregation of the variant with schizophrenia.

Main Methods:

  • Mini genes containing the del/ins variant were analyzed using primer-extension assays in NIH293 cells.
  • Association analysis was performed on additional schizophrenic cases and unaffected controls of African-American descent.
  • Family studies were conducted to examine allele cosegregation with psychiatric disease.

Main Results:

  • The del/ins variant in NMDAR1 intron 10 resulted in a fivefold enhancement of splicing, not disruption.
  • The mutant allele frequency was similar in schizophrenic patients and controls of African-American descent.
  • No significant cosegregation of the variant allele with psychiatric disease was observed in families.

Conclusions:

  • The investigated NMDAR1 intronic variant enhances splicing rather than disrupting it.
  • The variant does not appear to be a significant risk factor or causative mutation for schizophrenia in the studied African-American population.
  • Further research is needed to understand the functional implications of altered NMDAR1 splicing variants.

More Related Videos

A Novel Strategy Combining Array-CGH, Whole-exome Sequencing and In Utero Electroporation in Rodents to Identify Causative Genes for Brain Malformations08:22

A Novel Strategy Combining Array-CGH, Whole-exome Sequencing and In Utero Electroporation in Rodents to Identify Causative Genes for Brain Malformations

Published on: December 1, 2017

Dynamic Clamp Methods to Investigate Impaired Neuronal Excitability Associated with Autism08:44

Dynamic Clamp Methods to Investigate Impaired Neuronal Excitability Associated with Autism

Published on: October 17, 2025

Related Concept Videos

RNA Splicing01:32

RNA Splicing

Splicing is the process by which eukaryotic RNA is edited before its translation into protein. The RNA strand transcribed from eukaryotic DNA is called the primary transcript. The primary transcripts that become mRNAs are called precursor messenger RNAs (pre-mRNAs). Eukaryotic pre-mRNA contains alternating sequences of exons and introns. Exons are nucleotide sequences that code for proteins, whereas introns are the non-coding regions. In RNA splicing, introns are removed and exons are bonded...
RNA Splicing01:32

RNA Splicing

Splicing is the process by which eukaryotic RNA is edited before its translation into protein. The RNA strand transcribed from eukaryotic DNA is called the primary transcript. The primary transcripts that become mRNAs are called precursor messenger RNAs (pre-mRNAs). Eukaryotic pre-mRNA contains alternating sequences of exons and introns. Exons are nucleotide sequences that code for proteins, whereas introns are the non-coding regions. In RNA splicing, introns are removed and exons are bonded...
Chromatin Structure Regulates pre-mRNA Processing02:41

Chromatin Structure Regulates pre-mRNA Processing

In eukaryotic cells, nascent mRNA transcripts need to undergo many post-transcriptional modifications to reach the cell cytoplasm and translate into functional proteins. For a long time, transcription and pre-mRNA processing were considered two independent events that occur sequentially in the cell. However, it has now been well established that transcription and pre-mRNA processing are two simultaneous processes that are precisely regulated inside the cell.
The chromatin structure, especially...
Alternative RNA Splicing02:18

Alternative RNA Splicing

Alternative RNA splicing is the regulated splicing of exons and introns to produce different mature mRNAs from a single pre-mRNA. Unlike in constitutive splicing where a single gene produces a single type of mRNA, alternative splicing allows an organism to produce multiple proteins from a single gene and plays an important role in protein diversity.
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
Exon Recombination02:32

Exon Recombination

The evolution of new genes is critical for speciation. Exon recombination, also known as exon shuffling or domain shuffling, is an important means of new gene formation. It is observed across vertebrates, invertebrates, and in some plants such as potatoes and sunflowers. During exon recombination, exons from the same or different genes recombine and produce new exon-intron combinations, which might evolve into new genes. 
Exon shuffling follows “splice frame rules.” Each exon has three reading...
Biological Causes of Schizophrenia01:29

Biological Causes of Schizophrenia

Schizophrenia, a severe psychiatric disorder, arises from a complex interplay of biological factors, including genetic predisposition, structural brain abnormalities, neurotransmitter dysregulation, and developmental irregularities. These factors collectively contribute to the onset and progression of the disorder, which typically manifests in late adolescence or early adulthood.
Genetic Factors in Schizophrenia
The genetic basis of schizophrenia is strongly supported by family and twin studies.