Related Experiment Video
Updated: Dec 2, 2025
Array Comparative Genomic Hybridization Array CGH for Detection of Genomic Copy Number Variants
Published on: February 21, 2015
Lessons Learned from CNV Analysis of Major Birth Defects
Alina Christine Hilger1,2,3, Gabriel Clemens Dworschak1,2,3, Heiko Martin Reutter2,4
1Department of Pediatrics, Children's Hospital Medical Center, University Hospital Bonn, 53127 Bonn, Germany.
Abstract:
The treatment of major birth defects are key concerns for child health. Hitherto, for the majority of birth defects, the underlying cause remains unknown, likely to be heterogeneous. The implicated mortality and/or reduced fecundity in major birth defects suggest a significant fraction of mutational de novo events among the affected individuals. With the advent of systematic array-based molecular karyotyping, larger cohorts of affected individuals have been screened over the past decade. This review discusses the identification of disease-causing copy-number variations (CNVs) among individuals with different congenital malformations. It highlights the differences in findings depending on the respective congenital malformation. It looks at the differences in findings of CNV analysis in non-isolated complex congenital malformations, associated with central nervous system malformations or intellectual disabilities, compared to isolated single organ-system malformations. We propose that the more complex an organ system is, and the more genes involved during embryonic development, the more likely it is that mutational de novo events, comprising CNVs, will confer to the expression of birth defects of this organ system.
Insights
Major birth defects often stem from unknown causes. Copy-number variations (CNVs) are increasingly identified as key genetic contributors, especially in complex congenital malformations.
Area of Science:
- Genetics
- Developmental Biology
- Pediatric Health
Background:
- Major birth defects pose significant challenges in child health, with unknown etiologies for most cases.
- High mortality and reduced fecundity in major birth defects suggest a substantial role for de novo mutations.
- Recent advancements in molecular karyotyping have enabled large-scale screening of affected individuals.
Purpose of the Study:
- To review the identification of disease-causing copy-number variations (CNVs) in various congenital malformations.
- To analyze differences in CNV findings based on the type and complexity of congenital malformations.
- To explore the relationship between organ system complexity, gene involvement, and the occurrence of de novo CNVs in birth defects.
Main Methods:
- Systematic review of studies utilizing array-based molecular karyotyping.
- Analysis of large cohorts of individuals with congenital malformations.
- Comparative analysis of CNV findings in complex versus isolated malformations.
Main Results:
- Copy-number variations (CNVs) are identified as significant contributors to various congenital malformations.
- Distinct patterns of CNV findings emerge depending on the specific congenital malformation.
- Complex congenital malformations, particularly those involving the central nervous system or intellectual disabilities, show different CNV profiles compared to isolated malformations.
Conclusions:
- The complexity of an organ system and the number of genes involved in embryonic development correlate with the likelihood of de novo CNVs causing birth defects.
- CNV analysis is crucial for understanding the genetic basis of congenital malformations.
- Further research into de novo mutations, including CNVs, is warranted for improving diagnosis and treatment of birth defects.
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%...
02:46Genome Copying Errors
01:17Karyotyping
01:05Single Nucleotide Polymorphisms-SNPs
02:30Genomic Imprinting and Inheritance
The expression of some genes depends on which parent passed the gene to the offspring, through a phenomenon known as...