- Chip-based genotyping is a high-throughput molecular technique used to analyze genetic variations across an organism’s genome by detecting known DNA sequence differences, such as single nucleotide polymorphisms (SNPs), insertions and deletions (indels), or copy number variations (CNVs).
- It relies on microarray technology, where thousands to millions of oligonucleotide probes are immobilized on a small solid surface—commonly referred to as a “chip”—to capture and genotype specific regions of DNA simultaneously. This approach allows researchers to examine genetic diversity, identify disease-associated variants, and perform population-scale genetic analyses in a rapid, cost-effective, and highly parallelized manner.
- The principle behind chip-based genotyping involves the hybridization of fragmented, labeled DNA samples to complementary DNA probes fixed on the chip. Each probe is designed to target a specific genetic variant. After the DNA sample is applied to the chip, hybridization occurs if there is a perfect match between the probe and the sample DNA sequence. Fluorescent labeling is then used to detect these hybridization events, and high-resolution scanners measure the intensity of fluorescence signals to determine the genotype at each locus. This process enables the simultaneous interrogation of hundreds of thousands to millions of variants from a single DNA sample.
- Chip-based genotyping technologies have become indispensable in many areas of genomics research and clinical diagnostics. In genome-wide association studies (GWAS), they are used to identify genetic variants associated with complex diseases such as diabetes, cancer, cardiovascular disorders, and neurological conditions. In personalized medicine, chip-based assays help predict individual responses to drugs (pharmacogenomics), assess disease risk, and guide preventive or therapeutic strategies. They are also extensively employed in population genetics and evolutionary biology to study genetic diversity, ancestry, and migration patterns. In agriculture and livestock breeding, chip-based genotyping enables marker-assisted selection, trait mapping, and genomic selection to improve productivity and disease resistance.
- Clinically, chip-based platforms are also used for prenatal genetic screening, carrier testing, and oncology diagnostics, where they help identify specific mutations, chromosomal abnormalities, or somatic variants linked to cancer progression and treatment response. Additionally, they play a significant role in copy number variation (CNV) detection, which is critical for diagnosing conditions like developmental delay, intellectual disability, and certain congenital disorders.
- Despite its versatility and scalability, chip-based genotyping has some limitations. It is inherently dependent on prior knowledge of genetic variants, meaning it cannot discover novel mutations or structural variants that are not represented on the chip. The resolution is also limited compared to next-generation sequencing (NGS), which can provide base-pair level detail and detect rare variants. However, chip-based approaches remain a preferred choice in large-scale population studies, biobanking projects, and clinical testing where cost, throughput, and standardized analysis are crucial.
