scholarly journals Presence of pathogenic copy number variants (CNVs) is correlated with socioeconomic status

2019 ◽  
Vol 57 (1) ◽  
pp. 70-72 ◽  
Author(s):  
George J Burghel ◽  
Unzela Khan ◽  
Wei-Yu Lin ◽  
William Whittaker ◽  
Siddharth Banka
Keyword(s):  
Socioeconomic Status ◽  
General Population ◽  
Copy Number ◽  
De Novo ◽  
Copy Number Variants ◽  
Multiple Deprivation ◽  
Pathogenic Cnvs ◽  
Biological Determinants ◽  
Autosomal Copy ◽  
Index Of Multiple Deprivation

Socioeconomic status (SES) is a major determinant of health. We studied the Index of Multiple Deprivation Rank of 473 families with individuals with pathogenic autosomal copy number variants (CNVs) and known inheritance status. The IMDR distribution of families with pathogenic CNVs was significantly different from the general population. Families with inherited CNVs were significantly more likely to be living in areas of higher deprivation when compared with families that had individuals with de novo CNVs. These results provide unique insights into biological determinants of SES. As CNVs are relatively frequent in the general population, these results have important medical and policy consequences.

Genomic Syndromes in Schizophrenia

2013 ◽  
pp. 247-255
Author(s):  
George Kirov ◽  
Michael C. O’Donovan ◽  
Michael J. Owen
Keyword(s):  
Intellectual Disability ◽  
Developmental Delay ◽  
Neurodevelopmental Disorders ◽  
Copy Number ◽  
De Novo ◽  
Copy Number Variants ◽  
Individual Risk ◽  
Genomic Deletions ◽  
Pathogenic Cnvs ◽  
Cognition And Learning

Several submicroscopic genomic deletions and duplications known as copy number variants (CNVs) have been reported to increase susceptibility to schizophrenia. Those for which the evidence is particularly strong include deletions at chromosomal segments 1q21.1, 3q29, 15q11.2, 15q13.3, 17q12 and 22q11.2, duplications at 15q11.2-q13.1, 16p13.1, and 16p11.2, and deletions atthe gene NRXN1. The effect of each on individual risk is relatively large, but it does not appear that any of them is alone sufficient to cause disorder in carriers. These CNVs often arise as new mutations(de novo). Analyses of genes enriched among schizophrenia implicated CNVs highlight the involvement in the disorder of post-synaptic processes relevant to glutamatergicsignalling, cognition and learning. CNVs that contribute to schizophrenia risk also contribute to other neurodevelopmental disorders, including intellectual disability, developmental delay and autism. As a result of selection, all known pathogenic CNVs are rare, and none makes a sizeable contribution to overall population risk of schizophrenia, although the study of these mutations is nevertheless providing important insights into the origins of the disorder.

scholarly journals Trio-Based Low-Pass Genome Sequencing Reveals Characteristics and Significance of Rare Copy Number Variants in Prenatal Diagnosis

2021 ◽  
Vol 12 ◽  
Author(s):  
Matthew Hoi Kin Chau ◽  
Jicheng Qian ◽  
Zihan Chen ◽  
Ying Li ◽  
Yu Zheng ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Genome Sequencing ◽  
Copy Number ◽  
De Novo ◽  
Copy Number Variants ◽  
Recurrence Risk ◽  
Rare Cnvs ◽  
Pathogenic Cnvs ◽  
Low Pass ◽  
Clinically Significant

Background: Low-pass genome sequencing (GS) detects clinically significant copy number variants (CNVs) in prenatal diagnosis. However, detection at improved resolutions leads to an increase in the number of CNVs identified, increasing the difficulty of clinical interpretation and management.Methods: Trio-based low-pass GS was performed in 315 pregnancies undergoing invasive testing. Rare CNVs detected in the fetuses were investigated. The characteristics of rare CNVs were described and compared to curated CNVs in other studies.Results: A total of 603 rare CNVs, namely, 597 constitutional and 6 mosaic CNVs, were detected in 272 fetuses (272/315, 86.3%), providing 1.9 rare CNVs per fetus (603/315). Most CNVs were smaller than 1 Mb (562/603, 93.2%), while 1% (6/603) were mosaic. Forty-six de novo (7.6%, 46/603) CNVs were detected in 11.4% (36/315) of the cases. Eighty-four CNVs (74 fetuses, 23.5%) involved disease-causing genes of which the mode of inheritance was crucial for interpretation and assessment of recurrence risk. Overall, 31 pathogenic/likely pathogenic CNVs were detected, among which 25.8% (8/31) were small (<100 kb; n = 3) or mosaic CNVs (n = 5).Conclusion: We examined the landscape of rare CNVs with parental inheritance assignment and demonstrated that they occur frequently in prenatal diagnosis. This information has clinical implications regarding genetic counseling and consideration for trio-based CNV analysis.

scholarly journals An integrative approach to investigate the respective roles of single-nucleotide variants and copy-number variants in Attention-Deficit/Hyperactivity Disorder

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Leandro de Araújo Lima ◽  
Ana Cecília Feio-dos-Santos ◽  
Sintia Iole Belangero ◽  
Ary Gadelha ◽  
Rodrigo Affonseca Bressan ◽  
...  
Keyword(s):  
Attention Deficit Hyperactivity Disorder ◽  
Attention Deficit ◽  
Copy Number ◽  
De Novo ◽  
Copy Number Variants ◽  
Integrative Approach ◽  
Single Nucleotide Variants ◽  
Single Nucleotide ◽  
Hyperactivity Disorder ◽  
New Genes

Abstract Many studies have attempted to investigate the genetic susceptibility of Attention-Deficit/Hyperactivity Disorder (ADHD), but without much success. The present study aimed to analyze both single-nucleotide and copy-number variants contributing to the genetic architecture of ADHD. We generated exome data from 30 Brazilian trios with sporadic ADHD. We also analyzed a Brazilian sample of 503 children/adolescent controls from a High Risk Cohort Study for the Development of Childhood Psychiatric Disorders, and also previously published results of five CNV studies and one GWAS meta-analysis of ADHD involving children/adolescents. The results from the Brazilian trios showed that cases with de novo SNVs tend not to have de novo CNVs and vice-versa. Although the sample size is small, we could also see that various comorbidities are more frequent in cases with only inherited variants. Moreover, using only genes expressed in brain, we constructed two “in silico” protein-protein interaction networks, one with genes from any analysis, and other with genes with hits in two analyses. Topological and functional analyses of genes in this network uncovered genes related to synapse, cell adhesion, glutamatergic and serotoninergic pathways, both confirming findings of previous studies and capturing new genes and genetic variants in these pathways.

scholarly journals De Novo Sequence and Copy Number Variants are Strongly Associated with Tourette Disorder and Implicate Cell Polarity in Pathogenesis

2018 ◽  
Author(s):  
Sheng Wang ◽  
Jeffrey D. Mandelll ◽  
Yogesh Kumarr ◽  
Nawei Sunn ◽  
Montana T. Morris ◽  
...  
Keyword(s):  
Cell Polarity ◽  
Copy Number ◽  
De Novo ◽  
Copy Number Variants ◽  
Tourette Disorder

scholarly journals The prenatal diagnosis and clinical outcomes of fetuses with 15q11.2 copy number variants: a case series of 36 patients

2021 ◽  
Author(s):  
Jessica Kang ◽  
Chien Nan Lee ◽  
Yi-Ning Su ◽  
Ming-Wei Lin ◽  
Yi-Yun Tai ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Developmental Delay ◽  
Copy Number ◽  
De Novo ◽  
Copy Number Variants ◽  
Case Series ◽  
Copy Number Variant ◽  
University Hospital ◽  
Limited Information ◽  
Ultrasound Findings

Objective: The prenatal genetic counseling of fetus diagnosed with the 15q11.2 copy number variant (CNV) involving the BP1-BP2 region has been difficult due to limited information and controversial opinion on prognosis. Design: Case series. Setting: This study uses data from National Taiwan University Hospital. Sample: Data of 36 pregnant women who underwent prenatal microarray analysis from 2012 to 2017 and were assessed at National Taiwan University Hospital. Methods: Data were collected by reviewing patients’ medical record. Comparison of patient characteristics, prenatal ultrasound findings and postnatal outcomes between different cases involving the 15q11.2 BP1-BP2 region were presented. Main outcome measured: Postnatal prognosis. Results: Out of the 36 patients diagnosed with CNVs involving the BP1-BP2 region, 5 were diagnosed with microduplication and 31 with microdeletion. Abnormal ultrasound findings were recorded in 12 cases prenatally. De novo microduplications were observed in 25% of the cases and microdeletions were found in 14%. Amongst the cases, 10 pregnant women received termination of pregnancy and 26 gave birth to healthy individuals (27 babies in total). Conclusion: The prognoses of 15q11.2 CNVs were controversial and recent studies have revealed its connection with developmental delay and autism. In our study, no obvious developmental delay or neurological disorders were detected postnatally in the 1 case of 15q11.2 microduplication and 25 cases of microdeletion.

scholarly journals De Novo Sequence and Copy Number Variants Are Strongly Associated with Tourette Disorder and Implicate Cell Polarity in Pathogenesis

Cell Reports ◽  
2018 ◽  
Vol 24 (13) ◽  
pp. 3441-3454.e12 ◽  
Author(s):  
Sheng Wang ◽  
Jeffrey D. Mandell ◽  
Yogesh Kumar ◽  
Nawei Sun ◽  
Montana T. Morris ◽  
...  
Keyword(s):  
Cell Polarity ◽  
Copy Number ◽  
De Novo ◽  
Copy Number Variants ◽  
Tourette Disorder

Corrigendum to “Challenges in the clinical interpretation of small de novo copy number variants in neurodevelopmental disorders” [Gene 706 (2019) 162–171]

Gene ◽  
2020 ◽  
Vol 735 ◽  
pp. 144393
Author(s):  
Pamela Magini ◽  
Emanuela Scarano ◽  
Ilaria Donati ◽  
Alberto Sensi ◽  
Laura Mazzanti ◽  
...  
Keyword(s):  
Neurodevelopmental Disorders ◽  
Copy Number ◽  
De Novo ◽  
Copy Number Variants ◽  
Clinical Interpretation

Are paediatric stabbings in London related to socioeconomic status?

Trauma ◽  
2018 ◽  
Vol 21 (4) ◽  
pp. 310-316 ◽  
Author(s):  
Christine Lam ◽  
Christopher Aylwin ◽  
Mansoor Khan
Keyword(s):  
Socioeconomic Status ◽  
Penetrating Trauma ◽  
Trauma Centre ◽  
Interquartile Range ◽  
Negatively Associated ◽  
Multiple Deprivation ◽  
Deprivation Score ◽  
Major Trauma Centre ◽  
Increased Risk ◽  
Index Of Multiple Deprivation

Introduction Paediatric stabbings are on the increase across the United Kingdom, especially in large urban centres. Many London trauma centres are reporting a significant annual rise in the cases of penetrating trauma. Studies have shown victims with a lower socioeconomic status have an increased risk of paediatric penetrating trauma. This study aims to determine whether high depravity of an area increases the risk of paediatric stabbings in West London. We hypothesise that more deprived areas are likely to have a higher incidence of paediatric stabbings. Methods A retrospective review of data from the emergency department at a major trauma centre in West London was conducted using patient <18 years with a stabbing injury between March 2015 and July 2017. Gender, age, incident postcode and home postcode were collected. Socioeconomic status was measured using the 2015 English index of multiple deprivation. Incident postcode and home postcode were matched to an index of multiple deprivation decile, with 1 being the most deprived. Data were analysed using SPSS© Statistics 24. Results One hundred seventy-four cases were included; 97.7% of the cases were male and the mean age was 16 years. The location of the stabbings had a median index of multiple deprivation score of 3 (interquartile range = 3) with 61% of the cases occurring in areas with an index of multiple deprivation decile of 3 or less. Index of multiple deprivation decile from incident location and frequency of stabbing were strongly negatively associated (r = −0.85, p = 0.002). The victim’s home location had a median index of multiple deprivation score of 3 (interquartile range = 3) and 59.3% of victims living in areas with an index of multiple deprivation decile of less than 3. Again, they were strongly negatively associated (r = −0.85, p = 0.002). Conclusion The location of paediatric stabbings is associated with areas of high depravity and with victims from a more deprived background. To prevent paediatric stabbings, a multifactorial approach is required to increase the socioeconomic status of these areas.

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