| Title |
Post‐zygotic genomic changes in glutamate and dopamine pathway genes may explain discordance of monozygotic twins for schizophrenia
|
|---|---|
| Published in |
Clinical and Translational Medicine, November 2017
|
| DOI | 10.1186/s40169-017-0174-1 |
| Pubmed ID | |
| Authors |
C. A. Castellani, M. G. Melka, J. L. Gui, A. J. Gallo, R. L. O’Reilly, S. M. Singh |
| Abstract |
Monozygotic twins are valuable in assessing the genetic vs environmental contribution to diseases. In the era of complete genome sequences, they allow identification of mutational mechanisms and specific genes and pathways that offer predisposition to the development of complex diseases including schizophrenia. We sequenced the complete genomes of two pairs of monozygotic twins discordant for schizophrenia (MZD), including one representing a family tetrad. The family specific complete sequences have allowed identification of post zygotic mutations between MZD genomes. It allows identification of affected genes including relevant network and pathways that may account for the diseased state in pair specific patient. We found multiple twin specific sequence differences between co-twins that included small nucleotides [single nucleotide variants (SNV), small indels and block substitutions], copy number variations (CNVs) and structural variations. The genes affected by these changes belonged to a number of canonical pathways, the most prominent ones are implicated in schizophrenia and related disorders. Although these changes were found in both twins, they were more frequent in the affected twin in both pairs. Two specific pathway defects, glutamate receptor signaling and dopamine feedback in cAMP signaling pathways, were uniquely affected in the two patients representing two unrelated families. We have identified genome-wide post zygotic mutations in two MZD pairs affected with schizophrenia. It has allowed us to use the threshold model and propose the most likely cause of this disease in the two patients studied. The results support the proposition that each schizophrenia patient may be unique and heterogeneous somatic de novo events may contribute to schizophrenia threshold and discordance of the disease in monozygotic twins. |
X Demographics
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Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Canada | 2 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 50% |
| Scientists | 1 | 50% |
Mendeley readers
The data shown below were compiled from readership statistics for 40 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 40 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Bachelor | 10 | 25% |
| Researcher | 6 | 15% |
| Student > Ph. D. Student | 5 | 13% |
| Student > Master | 4 | 10% |
| Professor > Associate Professor | 3 | 8% |
| Other | 6 | 15% |
| Unknown | 6 | 15% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 9 | 23% |
| Biochemistry, Genetics and Molecular Biology | 8 | 20% |
| Agricultural and Biological Sciences | 5 | 13% |
| Neuroscience | 5 | 13% |
| Engineering | 2 | 5% |
| Other | 3 | 8% |
| Unknown | 8 | 20% |
Attention Score in Context
This research output has an Altmetric Attention Score of 17. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 30 January 2018.
All research outputs
#2,170,808
of 25,632,496 outputs
Outputs from Clinical and Translational Medicine
#86
of 1,077 outputs
Outputs of similar age
#46,926
of 448,374 outputs
Outputs of similar age from Clinical and Translational Medicine
#2
of 8 outputs
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