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Updated: Aug 26, 2025
Detection of Copy Number Alterations Using Single Cell Sequencing
Published on: February 17, 2017
Investigation of Copy Number Variation in South African Patients With Congenital Heart Defects
Nicole A Saacks1, James Eales2, Timothy F Spracklen1,3
1Division of Pediatric Cardiology, Department of Pediatrics and Child Health (N.A.S., T.F.S., T.A., J.L., G.C., R.D.D., L.S., A.J., L.J.Z.).
Insights
This study identified copy number variants (CNVs) in South African children with congenital heart disease (CHD), revealing genetic factors similar to European populations. Novel candidate genes for CHD were also discovered in this diverse cohort.
Area of Science:
- Genetics
- Pediatrics
- Genomics
Background:
- Congenital heart disease (CHD) is a major global cause of childhood illness and death.
- Genetic factors, including copy number variants (CNVs), are implicated in CHD risk, particularly in European populations.
- The role of rare CNVs in African CHD populations remains largely unexplored.
Purpose of the Study:
- To identify pathogenic and likely pathogenic CNVs in South African patients diagnosed with CHD.
- To investigate the genetic underpinnings of CHD in an African pediatric cohort.
Main Methods:
- Genotyping of 90 nonsyndromic CHD patients using the Affymetrix CytoScan HD platform.
- Identification of large, rare CNVs in known CHD-associated and candidate genes.
Main Results:
- Eight CNVs were found in known CHD-associated genes (e.g., GATA4, TBX1) in six patients.
- CNVs in five candidate genes (e.g., DGCR8, JARID2) were identified in five patients.
- A 6.7% overall discovery yield was achieved, with 5.6% of patients harboring pathogenic or likely pathogenic CNVs.
Conclusions:
- Chromosomal microarray is effective for identifying CNVs in African CHD patients.
- Genetic findings in this cohort are comparable to those in European CHD studies.
- Novel potential CHD genes were identified, highlighting the importance of studying diverse populations.
Background:
Congenital heart disease (CHD) is a leading non-infectious cause of pediatric morbidity and mortality worldwide. Although the etiology of CHD is poorly understood, genetic factors including copy number variants (CNVs) contribute to the risk of CHD in individuals of European ancestry. The presence of rare CNVs in African CHD populations is unknown. This study aimed to identify pathogenic and likely pathogenic CNVs in South African patients with CHD.
Methods:
Genotyping was performed on 90 patients with nonsyndromic CHD using the Affymetrix CytoScan HD platform. These data were used to identify large, rare CNVs in known CHD-associated genes and candidate genes.
Results:
We identified eight CNVs overlapping known CHD-associated genes (GATA4, CRKL, TBX1, FLT4, B3GAT3, NSD1) in six patients. The analysis also revealed CNVs encompassing five candidate genes likely to play a role in the development of CHD (DGCR8, KDM2A, JARID2, FSTL1, CYFIP1) in five patients. One patient was found to have 47, XXY karyotype. We report a total discovery yield of 6.7%, with 5.6% of the cohort carrying pathogenic or likely pathogenic CNVs expected to cause the observed phenotypes.
Conclusions:
In this study, we show that chromosomal microarray is an effective technique for identifying CNVs in African patients diagnosed with CHD and have demonstrated results similar to previous CHD genetic studies in Europeans. Novel potential CHD genes were also identified, indicating the value of genetic studies of CHD in ancestrally diverse populations.
Related Concept Videos
02:26Comparing Copy Number Variations and SNPs
Copy number variations or CNVs are the structural variations that cover more than 1kb of DNA sequence. The single nucleotide polymorphism (SNP), on the other hand, is a single nucleotide change or a point mutation that is found in more than 1%...
01:05Single Nucleotide Polymorphisms-SNPs