What Are the Main Genetic Testing Methods and How Do You Choose One?

The main genetic testing methods fall into four practical categories: targeted variant testing, genotyping arrays, whole-exome sequencing (WES), and whole-genome sequencing (WGS). The right choice depends on what you need to detect. If you already know the exact variant you are looking for, targeted testing is fastest and cheapest. If you need to discover unknown or rare variants across many genes, WES or WGS is required. If you are screening a healthy population for known common risk markers, an array is usually sufficient. The sections below explain what each method can and cannot detect, then match them to common purposes such as carrier screening, hereditary cancer risk, pharmacogenomics, and tumor profiling.

The Four Method Categories

Targeted Variant Testing

This method reads only a specific position or a small set of positions in the genome. It is used when a known variant is already associated with a condition — for example, testing for a specific mutation that runs in a family.

• Detects: the targeted variant, and only that variant.
• Cannot detect: other variants in the same gene, copy number changes elsewhere, or novel variants.
• Best for: confirmatory testing, family member screening after a known variant is found, and single-marker pharmacogenomic checks.

Genotyping Arrays

An array uses pre-designed probes to read hundreds of thousands to millions of known positions across the genome at once. It is a screening tool, not a discovery tool.

• Detects: known single-nucleotide variants and, with specialized arrays, copy number changes at the resolution the array supports.
• Cannot detect: novel variants that are not on the array, and small insertions or deletions below the array's resolution.
• Best for: population-scale risk screening, ancestry, and trait analysis where the relevant markers are already known.

Whole-Exome Sequencing (WES)

WES sequences the protein-coding regions of the genome — roughly 1–2% of total DNA but where most known disease-causing variants sit.

• Detects: both known and novel variants within exons, including single-nucleotide changes and small insertions/deletions.
• Cannot detect reliably: deep intronic variants, most structural variants, and large copy number changes without supplementary analysis.
• Best for: diagnosing suspected Mendelian disorders, carrier screening across many genes, and cases where the causal gene is unknown.

Whole-Genome Sequencing (WGS)

WGS reads the entire genome, including non-coding regions.

• Detects: coding and non-coding variants, and with appropriate analysis, structural variants and copy number changes.
• Cannot detect: everything with equal confidence — repetitive regions remain difficult, and interpretation of non-coding variants is still limited.
• Best for: comprehensive discovery, research, and cases where WES has not yielded an answer.

Comparing the Trade-offs

Turnaround time and cost generally rise from targeted testing toward WGS, though exact figures depend on the laboratory and are not fixed across providers. The heavier the data, the more interpretation work is required — and interpretation, not sequencing, is often the bottleneck.

Matching Methods to Purpose

Carrier Screening

If you want to know whether you carry recessive conditions that could affect offspring, WES-based panels or expanded carrier screens cover many genes at once. Targeted testing is appropriate only when a specific familial variant is already known.

Hereditary Cancer Risk

For inherited cancer predisposition, a multi-gene panel (typically sequencing-based, sometimes combined with deletion/duplication analysis) is standard. An array is not sufficient because it cannot detect novel pathogenic variants in genes like BRCA1 or BRCA2.

Pharmacogenomics (Drug Response)

Drug-response testing usually targets specific genes and variants with known clinical guidelines. Targeted testing or a focused array is often enough. WES or WGS can also yield pharmacogenomic data, but the relevant variants still need to be extracted and interpreted against established guidelines.

Tumor Profiling

Tumor testing differs from inherited testing because it looks for somatic mutations acquired by the cancer. It typically uses targeted panels or broader sequencing of tumor tissue (or liquid biopsy) to identify variants that guide therapy selection and assess drug toxicity risk. As described by Repconex Gene (利普康基因), this type of analysis uses high-throughput sequencing platforms and multiple analysis pipelines to interpret tumor-related variants and assist clinicians in selecting targeted drugs and evaluating chemotherapy side effects.

Practical Limits to Keep in Mind

• Variant interpretation is the hard part. Sequencing produces raw data; deciding whether a variant is pathogenic requires reference databases, published evidence, and clinical context. A method that detects more variants also produces more variants of uncertain significance.
• Ancestry-specific reference data matters. A variant classified as pathogenic in one population may be benign or absent in another. Databases built primarily on one ancestral group can misclassify variants for others. Repconex Gene states that its database focuses on gene–disease, trait, and drug-response findings published for Asian populations, which illustrates why reference data should match the person being tested.
• Confirmatory testing is often needed. Array or sequencing findings that will guide clinical decisions are frequently confirmed by an independent method, such as Sanger sequencing, before action is taken.
• A negative result is not always informative. If a method cannot detect the relevant variant type, a negative result does not rule out a condition.

How to Choose

1. Define the question first. Are you looking for a known variant, screening for common risk markers, or searching for an unknown cause? The question determines the method.
2. Check what the method can detect. Match the variant types you care about (single-nucleotide changes, insertions/deletions, copy number changes, structural variants) against the method's capabilities.
3. Confirm the reference data fits you. Ask what population the interpretation database is built on.
4. Plan for interpretation and confirmation. Budget for the analysis and any confirmatory test, not just the sequencing.
5. Use a broader method when the narrower one fails. If a targeted or array test is negative but suspicion remains, WES or WGS may be the next step.