Copy Number Variations (CNVs) represent a significant aspect of human genetic diversity, involving differences in the number of copies of specific DNA segments among individuals. These variations are a type of structural alteration within the genome, meaning they involve larger changes to the DNA structure than single-letter variations. Studying these genomic differences helps scientists gain insight into the genetic underpinnings of various conditions.
Understanding Copy Number Variations
CNVs are segments of DNA that are present in a variable number of copies within the genomes of different individuals. These variations are broadly categorized into two main types: deletions, where a segment of DNA is missing, and duplications, where an extra copy of a DNA segment is present. These segments can range significantly in size, from small stretches of DNA containing only a few base pairs to large regions spanning multiple genes. These structural differences often involve segments exceeding 1 kilobase in length and can affect one or more genes. While some CNVs are common and do not cause any health issues, others can have considerable biological effects due to their impact on gene dosage.
How CNVs Influence Health
CNVs can significantly influence health by altering gene dosage, which refers to the number of copies of a particular gene an individual possesses. This alteration can lead to either an excess or a deficiency of gene products, disrupting normal cellular processes. For example, a duplication of a gene encoding a transcription factor might lead to increased expression of its target genes, while a deletion could result in decreased expression.
These genomic changes are associated with a range of genetic disorders, including developmental delays, intellectual disabilities, and autism spectrum disorder. Studies indicate that rare CNVs are frequently observed in individuals with autism spectrum disorder, contributing to approximately 5-10% of cases. CNVs can also contribute to congenital anomalies and increase susceptibility to complex conditions such as certain neurological or psychiatric disorders.
For instance, variations in the amylase gene copy number are linked to dietary adaptations, with populations consuming more starchy foods typically having more copies. This illustrates how some CNVs can confer an evolutionary advantage without causing disease, showcasing the varied impact of these genomic alterations.
Identifying CNVs Through Testing
Detecting CNVs in a clinical setting often involves specialized laboratory techniques designed to identify these structural variations in an individual’s genome. Chromosomal microarray analysis (CMA) has been a standard method for identifying CNVs in individuals with unexplained developmental differences, intellectual disabilities, or congenital anomalies. CMA works by comparing a patient’s DNA to a reference genome to detect deletions or duplications across chromosomes.
Next-generation sequencing (NGS) is another powerful technique used for CNV detection, offering higher resolution and increased coverage compared to traditional methods. NGS can detect smaller or novel CNVs that array-based methods might miss, and it can precisely map their genomic locations. These tests are used when there is a suspicion of a genetic condition linked to copy number changes, providing valuable information for diagnosis and genetic counseling.