How Whole-Genome Testing Differs from PCR and Other Methods

Most people picture a genetic test as the search for one known trait. A PCR test for COVID looks for viral RNA. A paternity test compares the same stretch of DNA in two people. A hereditary cancer test looks for one of the known pathogenic variants in the gene BRCA1 (breast cancer gene 1). In each of these examples the laboratory knows in advance exactly what to look for, and the answer is always narrow: is this specific marker present in the sample or not.

Whole-genome testing operates on a different logic. Instead of checking one chosen point, it simultaneously reads millions of points across the genome, without any prior hypotheses about the role of each individual point. The term "genetic test" remains common to both approaches. The tasks they address are substantially different.

How a genetic test differs from a blood test — DNA Test and Blood Test: What Is the Difference

The Method of Genetic Testing Determines How Complete and Accurate the Result Will Be

Genetics has at least three distinct technologies for reading DNA, and each produces a result of a different nature:

1. PCR (polymerase chain reaction) checks one pre-selected stretch of DNA and gives a precise answer about that stretch alone.

2. Genotyping reads hundreds of thousands of points simultaneously — a volume sufficient for assessing polygenic risks.

3. Whole genome sequencing (WGS) determines the sequence of every nucleotide without any prior constraints — for tasks that require a maximally complete picture.

These are NOT three quality levels of the same test, where one method is "better" than another. They are three distinct tools that answer three questions of different scope: about one point, about hundreds of thousands of points, or about the entire genome.

How PCR Works: One Answer to One Specific Question

PCR is a widely used method of laboratory diagnostics. The laboratory synthesises an artificial primer — a short DNA fragment that matches only one pre-specified genetic target. If that target is present in the sample, the instrument amplifies it, copying it repeatedly until the signal is strong enough to be detected. If the target is absent, no amplification occurs, and there is no signal. The result is always binary: present or absent.

During the pandemic, PCR made it possible to rapidly and accurately identify specific mutations in variants of SARS-CoV-2, distinguishing Delta from Omicron, for example (Esman et al., Diagnostics, 2022). In clinical oncogenetics, the same principle underlies targeted testing for a pathogenic variant already confirmed in a family — in BRCA1 or BRCA2 (breast cancer gene 2): once a specific variant has been confirmed in one relative, other family members are tested for that variant rather than for the entire gene (Samadder et al., JAMA Oncol., 2021).

PCR works exclusively with what it is told to look for. Anything outside the chosen target simply does not exist for this method.

How Genotyping Works: Scanning the Genome at Hundreds of Thousands of Points Simultaneously

Every genotyping result rests on two components: the GSA (Global Screening Array, Illumina) platform, which physically reads the sample, and the GWAS (Genome-Wide Association Study) database, which provides the scientific context for interpretation. Together they allow more than 600,000 genomic points to be read simultaneously using a microarray chip whose surface carries an equal number of molecular probes.

Each such point is a SNP (single-nucleotide polymorphism) — a position in the genome where different versions of one DNA "letter" occur naturally across the population. The instrument reads signals from all points simultaneously and converts them into a digital genotype profile for the individual (Verlouw et al., Eur. J. Hum. Genet., 2021). The scale of this approach is illustrated by large biobanks: one of the best-known projects read genomic arrays on chips from nearly 500,000 participants simultaneously, generating data across hundreds of thousands of points per sample (Bycroft et al., Nature, 2018).

Why Searching for a Single Mutation Cannot Assess Polygenic Risk

Most common conditions and predispositions analysed by Apixmed Prism are not determined by a single fault in a single gene. They are shaped by the simultaneous action of thousands of genetic variants, each of which has a minimal individual effect. Decades of GWAS studies — involving large-scale comparisons of genomes from hundreds of thousands of participants — have established which of the 600,000-plus chip points are statistically associated with specific predispositions or conditions (Uffelmann et al., Nat. Rev. Methods Primers, 2021). The sum of these associations is used to calculate a PRS (Polygenic Risk Score).

Genotyping generates precisely the data array needed for such calculations: hundreds of thousands of points simultaneously, each with pre-established weight coefficients from GWAS studies. PCR cannot reproduce this array — it checks one point at a time, and scaling it to thousands of targets simultaneously is technically impractical.

Whole Genome Sequencing: No Pre-Selected Points

WGS determines the sequence of each of the approximately 3 billion nucleotides in human DNA, without any pre-selected targets or points. It is particularly useful when searching for rare, as-yet-undescribed variants — for example, in complex oncological or rare disease clinical cases where a pre-defined set of points does not cover the relevant region.

Apixmed Prism supports both approaches — genotyping and whole genome sequencing. For most indicators covered by the report, polygenic analysis based on either method yields a comparable, clinically meaningful result, because the key variants used in the calculations are well represented in both cases. The difference between approaches becomes more significant when searching for rare or novel variants, which falls outside the scope of standard polygenic analysis.

What This Means for Someone Taking the Test

When you see the phrase "approximately 600,000 genetic markers are analysed," this is not about a single disease or a single predisposition. It means that a single saliva sample can be examined across dozens of different areas simultaneously — assessing caffeine sensitivity, inherited characteristics of vitamin absorption, and hundreds of other indicators, without the need to take a separate targeted test for each individual question.

Three tools for three different tasks

PCR is appropriate for point-specific checks: confirming the presence of a pathogen's DNA, verifying a known mutation, establishing paternity. Genotyping provides simultaneous access to hundreds of thousands of genomic points, enabling polygenic analysis and delivering the precise data volume needed for risk calculations — at a reasonable cost and within a practical timeframe. Whole genome sequencing is used for tasks that require a complete picture with no prior constraints on coverage.

Find out which genetic markers Prism analyses →

Frequently Asked Questions

How does genotyping differ from PCR?

PCR checks one pre-specified stretch of DNA; genotyping reads hundreds of thousands of points simultaneously. PCR gives a binary "present / absent" answer for a specific target (Esman et al., Diagnostics, 2022). Genotyping generates a signal array from more than 600,000 points at once, enabling assessment of traits influenced jointly by thousands of variants (Verlouw et al., Eur. J. Hum. Genet., 2021).

How do researchers know which SNPs matter for calculating PRS?

This information comes from large-scale GWAS studies. They compare genomes from hundreds of thousands of participants to establish which specific SNPs are statistically associated with particular traits or conditions (Uffelmann et al., Nat. Rev. Methods Primers, 2021). Without this data, the signals read by the chip would have no interpretation.

Does Apixmed Prism analyse the entire genome in the same detail as WGS?

The Apixmed Prism report supports both approaches — genotyping and whole genome sequencing. Genotyping reads pre-defined genomic positions, whereas WGS determines the sequence of every nucleotide. For assessing inherited characteristics and polygenic risks, both methods yield a clinically meaningful result. The difference becomes significant when searching for rare or not-yet-catalogued variants.

Why can't PCR assess polygenic risk?

PCR checks one target at a time, while assessing polygenic risk requires checking thousands of variants simultaneously. Complex traits and common conditions are shaped by the cumulative effect of thousands of genetic variants. Scaling PCR to that many targets at once is technically impractical — genotyping is the method used for this purpose.

Can genotyping detect a rare, previously undescribed mutation?

Genotyping is limited to a pre-defined set of points. The chip reads only those genomic positions that were built into it during manufacture. Searching for entirely new, not-yet-catalogued variants is the task of whole genome sequencing.

Genetic test results are not a diagnosis and do not replace a consultation with a doctor. The Apixmed Prism report provides genetic context that complements clinical test results and supports informed decision-making together with your physician.

Sources

1. Uffelmann, E., Huang, Q. Q., Munung, N. S. et al. (2021). Genome-wide association studies. Nature Reviews Methods Primers, 1, Article 59.https://doi.org/10.1038/s43586-021-00056-9

2. Verlouw, J. A. M., Clemens, E., de Vries, J. H. et al. (2021). A comparison of genotyping arrays. European Journal of Human Genetics, 29(11), 1611–1624.https://doi.org/10.1038/s41431-021-00917-7

3. Bycroft, C., Freeman, C., Petkova, D. et al. (2018). The UK Biobank resource with deep phenotyping and genomic data. Nature, 562, 203–209.https://doi.org/10.1038/s41586-018-0579-z

4. Esman, A., Cherkashina, A., Mironov, K. et al. (2022). SARS-CoV-2 Variants Monitoring Using Real-Time PCR. Diagnostics, 12(10), 2388.https://doi.org/10.3390/diagnostics12102388

5. Samadder, N. J., Riegert-Johnson, D., Boardman, L. et al. (2021). Comparison of Universal Genetic Testing vs Guideline-Directed Targeted Testing for Patients With Hereditary Cancer Syndrome. JAMA Oncology, 7(2), 230–237.https://doi.org/10.1001/jamaoncol.2020.6252