Copy number variations in 119 Chinese children with idiopathic short stature identified by the custom genome-wide microarray

Abstract Background Congenital heart disease (CHD) is one of the most common birth defects. Copy number variations (CNVs) have been proved to be important genetic factors that contribute to CHD. Here we screened genome-wide CNVs in Chinese children with complete atrioventricular canal (CAVC) and single ventricle (SV), since there were scarce researches dedicated to these two types of CHD. Methods We screened CNVs in 262 sporadic CAVC cases and 259 sporadic SV cases respectively, using a customized SNP array. The detected CNVs were annotated and filtered using available databases. Results Among 262 CAVC patients, we identified 6 potentially-causative CNVs in 43 individuals (16.41%, 43/262), including 2 syndrome-related CNVs (7q11.23 and 8q24.3 deletion). Surprisingly, 90.70% CAVC patients with detected CNVs (39/43) were found to carry duplications of 21q11.2–21q22.3, which were recognized as trisomy 21 (Down syndrome, DS). In CAVC with DS patients, the female to male ratio was 1.6:1.0 (24:15), and the rate of pulmonary hypertension (PH) was 41.03% (16/39). Additionally, 6 potentially-causative CNVs were identified in the SV patients (2.32%, 6/259), and none of them was trisomy 21. Most CNVs identified in our cohort were classified as rare (< 1%), occurring just once among CAVC or SV individuals except the 21q11.2–21q22.3 duplication (14.89%) in CAVC cohort. Conclusions Our study identified 12 potentially-causative CNVs in 262 CAVC and 259 SV patients, representing the largest cohort of these two CHD types in Chinese population. The results provided strong correlation between CAVC and DS, which also showed sex difference and high incidence of PH. The presence of potentially-causative CNVs suggests the etiology of complex CHD is incredibly diverse, and CHD candidate genes remain to be discovered.

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Combination of Genome-Wide Polymorphisms and Copy Number Variations of Pharmacogenes in Koreans

Journal of Personalized Medicine ◽

10.3390/jpm11010033 ◽

2021 ◽

Vol 11 (1) ◽

pp. 33

Author(s):

Nayoung Han ◽

Jung Mi Oh ◽

In-Wha Kim

Keyword(s):

Copy Number ◽

Genome Wide Association Study ◽

Copy Number Gain ◽

Copy Number Variations ◽

Gene Gain ◽

Single Nucleotide Variants ◽

Single Nucleotide ◽

Haplotype Blocks ◽

Genome Wide ◽

Control And Prevention

For predicting phenotypes and executing precision medicine, combination analysis of single nucleotide variants (SNVs) genotyping with copy number variations (CNVs) is required. The aim of this study was to discover SNVs or common copy CNVs and examine the combined frequencies of SNVs and CNVs in pharmacogenes using the Korean genome and epidemiology study (KoGES), a consortium project. The genotypes (N = 72,299) and CNV data (N = 1000) were provided by the Korean National Institute of Health, Korea Centers for Disease Control and Prevention. The allele frequencies of SNVs, CNVs, and combined SNVs with CNVs were calculated and haplotype analysis was performed. CYP2D6 rs1065852 (c.100C>T, p.P34S) was the most common variant allele (48.23%). A total of 8454 haplotype blocks in 18 pharmacogenes were estimated. DMD ranked the highest in frequency for gene gain (64.52%), while TPMT ranked the highest in frequency for gene loss (51.80%). Copy number gain of CYP4F2 was observed in 22 subjects; 13 of those subjects were carriers with CYP4F2*3 gain. In the case of TPMT, approximately one-half of the participants (N = 308) had loss of the TPMT*1*1 diplotype. The frequencies of SNVs and CNVs in pharmacogenes were determined using the Korean cohort-based genome-wide association study.

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Genome-wide copy number variations as molecular diagnostic tool for cutaneous intermediate melanocytic lesions: a systematic review and individual patient data meta-analysis

Virchows Archiv ◽

10.1007/s00428-021-03095-5 ◽

2021 ◽

Author(s):

Chiel F. Ebbelaar ◽

Anne M. L. Jansen ◽

Lourens T. Bloem ◽

Willeke A. M. Blokx

Keyword(s):

Systematic Review ◽

Sensitivity And Specificity ◽

Copy Number ◽

Individual Patient Data ◽

Meta Analysis ◽

Copy Number Variations ◽

Patient Data ◽

Melanocytic Lesions ◽

Genome Wide ◽

Malignant Lesions

AbstractCutaneous intermediate melanocytic neoplasms with ambiguous histopathological features are diagnostically challenging. Ancillary cytogenetic techniques to detect genome-wide copy number variations (CNVs) might provide a valuable tool to allow accurate classification as benign (nevus) or malignant (melanoma). However, the CNV cut-off value to distinguish intermediate lesions from melanoma is not well defined. We performed a systematic review and individual patient data meta-analysis to evaluate the use of CNVs to classify intermediate melanocytic lesions. A total of 31 studies and 431 individual lesions were included. The CNV number in intermediate lesions (median 1, interquartile range [IQR] 0–2) was significantly higher (p<0.001) compared to that in benign lesions (median 0, IQR 0–1) and lower (p<0.001) compared to that in malignant lesions (median 6, IQR 4–11). The CNV number displayed excellent ability to differentiate between intermediate and malignant lesions (0.90, 95% CI 0.86–0.94, p<0.001). Two CNV cut-off points demonstrated a sensitivity and specificity higher than 80%. A cut-off of ≥3 CNVs corresponded to 85% sensitivity and 84% specificity, and a cut-off of ≥4 CNVs corresponded to 81% sensitivity and 91% specificity, respectively. This individual patient data meta-analysis provides a comprehensive overview of CNVs in cutaneous intermediate melanocytic lesions, based on the largest pooled cohort of ambiguous melanocytic neoplasms to date. Our meta-analysis suggests that a cut-off of ≥3 CNVs might represent the optimal trade-off between sensitivity and specificity in clinical practice to differentiate intermediate lesions from melanoma.

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High-resolution genome-wide array-CGH reveals copy number variations associated with premature ovarian failure

Placenta ◽

10.1016/j.placenta.2011.07.029 ◽

2011 ◽

Vol 32 ◽

pp. S282

Author(s):

Paola Scaruffi ◽

Sara Stigliani ◽

Annamaria Jane Nicoletti ◽

Pier Luigi Venturini ◽

Gian Paolo Tonini ◽

...

Keyword(s):

High Resolution ◽

Premature Ovarian Failure ◽

Copy Number ◽

Array Cgh ◽

Copy Number Variations ◽

Ovarian Failure ◽

Genome Wide

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Genome-wide Association of Copy-Number Variation Reveals an Association between Short Stature and the Presence of Low-Frequency Genomic Deletions

The American Journal of Human Genetics ◽

10.1016/j.ajhg.2011.10.014 ◽

2011 ◽

Vol 89 (6) ◽

pp. 751-759 ◽

Cited By ~ 45

Author(s):

Andrew Dauber ◽

Yongguo Yu ◽

Michael C. Turchin ◽

Charleston W. Chiang ◽

Yan A. Meng ◽

...

Keyword(s):

Copy Number Variation ◽

Short Stature ◽

Copy Number ◽

Low Frequency ◽

Genome Wide Association ◽

Genomic Deletions ◽

Genome Wide ◽

Number Variation

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Genome-wide burden and association analyses implicate copy number variations in asthma risk among children and young adults from Latin America

Scientific Reports ◽

10.1038/s41598-018-32837-w ◽

2018 ◽

Vol 8 (1) ◽

Cited By ~ 3

Author(s):

Pablo Oliveira ◽

Gustavo N. O. Costa ◽

Andresa K. A. Damasceno ◽

Fernando P. Hartwig ◽

George C. G. Barbosa ◽

...

Keyword(s):

Young Adults ◽

Latin America ◽

Copy Number ◽

Copy Number Variations ◽

Association Analyses ◽

Asthma Risk ◽

Genome Wide ◽

Children And Young Adults

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Detection of genome-wide copy number variations in two chicken lines divergently selected for abdominal fat content

BMC Genomics ◽

10.1186/1471-2164-15-517 ◽

2014 ◽

Vol 15 (1) ◽

pp. 517 ◽

Cited By ~ 16

Author(s):

Hui Zhang ◽

Zhi-Qiang Du ◽

Jia-Qiang Dong ◽

Hai-Xia Wang ◽

Hong-Yan Shi ◽

...

Keyword(s):

Copy Number ◽

Copy Number Variations ◽

Abdominal Fat ◽

Fat Content ◽

Genome Wide

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Clinical and Molecular Evaluation of SHOX/PAR1 Duplications in Léri-Weill Dyschondrosteosis (LWD) and Idiopathic Short Stature (ISS)

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2010-1689 ◽

2011 ◽

Vol 96 (2) ◽

pp. E404-E412 ◽

Cited By ~ 41

Author(s):

S. Benito-Sanz ◽

E. Barroso ◽

D. Heine-Suñer ◽

A. Hisado-Oliva ◽

V. Romanelli ◽

...

Keyword(s):

Short Stature ◽

Skeletal Dysplasia ◽

Copy Number ◽

Clinical Manifestations ◽

Idiopathic Short Stature ◽

Pseudoautosomal Region ◽

Height Gain ◽

Multiple Copies ◽

Copy Number Changes ◽

Design And Methods

abstract Context: Léri-Weill dyschondrosteosis (LWD) is a skeletal dysplasia characterized by disproportionate short stature and the Madelung deformity of the forearm. SHOX mutations and pseudoautosomal region 1 deletions encompassing SHOX or its enhancers have been identified in approximately 60% of LWD and approximately 15% of idiopathic short stature (ISS) individuals. Recently SHOX duplications have been described in LWD/ISS but also in individuals with other clinical manifestations, thus questioning their pathogenicity. Objective: The objective of the study was to investigate the pathogenicity of SHOX duplications in LWD and ISS. Design and Methods: Multiplex ligation-dependent probe amplification is routinely used in our unit to analyze for SHOX/pseudoautosomal region 1 copy number changes in LWD/ISS referrals. Quantitative PCR, microsatellite marker, and fluorescence in situ hybridization analysis were undertaken to confirm all identified duplications. Results: During the routine analysis of 122 LWD and 613 ISS referrals, a total of four complete and 10 partial SHOX duplications or multiple copy number (n > 3) as well as one duplication of the SHOX 5′ flanking region were identified in nine LWD and six ISS cases. Partial SHOX duplications appeared to have a more deleterious effect on skeletal dysplasia and height gain than complete SHOX duplications. Importantly, no increase in SHOX copy number was identified in 340 individuals with normal stature or 104 overgrowth referrals. Conclusion: MLPA analysis of SHOX/PAR1 led to the identification of partial and complete SHOX duplications or multiple copies associated with LWD or ISS, suggesting that they may represent an additional class of mutations implicated in the molecular etiology of these clinical entities.

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