This and That Strands: Why Your DNA Testing Results Feel So Confusing

This and That Strands: Why Your DNA Testing Results Feel So Confusing

You’ve probably seen the ads. A smiling person spits into a plastic tube, mails it off, and suddenly "discovers" they are 12% something they never expected. It’s a compelling narrative. But when you actually open your raw data or look at the fine print of a genetic report, you start seeing terms like this and that strands or "forward and reverse" orientations. Honestly, it’s a mess. Most people think DNA is a simple blueprint, but it's more like a double-sided mirror where the image changes depending on which side you’re standing on.

DNA doesn't just sit there. It has directionality.

If you’ve ever felt like your ancestry results or health markers don't quite match up between different platforms—say, 23andMe versus AncestryDNA—you aren't crazy. The discrepancy often boils down to how these companies report this and that strands. It’s a fundamental part of molecular biology that most consumer interfaces hide behind pretty percentages and colorful maps.

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The Reality of the Double Helix

DNA is antiparallel. That’s the scientific way of saying the two strands run in opposite directions. Think of it like a two-way street. One side goes north, the other goes south. In genetics, we call these the 5' (five prime) and 3' (three prime) ends.

When a lab sequences your "this and that strands," they are looking at the nitrogenous bases: Adenine (A), Thymine (T), Cytosine (C), and Guanine (G). Because of how chemistry works, A always pairs with T, and C always pairs with G. This is known as Watson-Crick base pairing.

So, if one strand has an A, the other must have a T.

The "this" strand might be the coding strand (the one that actually carries the instructions for a protein), while the "that" strand is the template. Or, more commonly in the world of SNP (Single Nucleotide Polymorphism) chips used by commercial companies, one is the "Forward" strand and the other is the "Reverse."

It gets tricky.

If a company reports your genotype based on the forward strand, they might say you have a "G." But if another company looks at the reverse strand for that same spot in your genome, they’ll report a "C." You haven't mutated. The data is the same. The perspective just shifted. This is the "strand flip" problem, and it’s the bane of existence for amateur genealogists and biohackers alike.

Why Your Raw Data Looks Like Gibberish

When you download your raw data, you see a long list of RSIDs (Reference SNP cluster IDs) and then your "genotype"—usually two letters like AA, CT, or GG.

But which strand are those letters on?

Back in the day, the Human Genome Project established a "Reference Genome." This is basically the master map. However, the map gets updated. We’re currently using versions like GRCh37 or GRCh38. Sometimes, between updates, the way a specific this and that strand is oriented can change in the official records.

Let’s look at a real-world example: the MTHFR gene. It’s incredibly popular in wellness circles. People obsess over the C677T mutation. If you’re looking at your data, you might see a CC, or maybe a TT. But if your report says AA, you’re likely looking at the complementary sequence on the opposite strand.

It’s easy to panic. You might think you have a rare mutation when, in reality, you’re just reading the "that" strand instead of the "this" strand.

The Ambiguous SNP Nightmare

There are certain points in your DNA where a "strand flip" is impossible to detect without more info. These are the A/T and C/G SNPs.

Imagine your DNA has an Adenine (A) on one side and a Thymine (T) on the other. If you have a mutation where that pair flips, you still have an A and a T. You just don't know which is on which strand. These are called palindromic SNPs. They are the "ambiguous" parts of the this and that strands conversation. Without knowing the orientation (the "top" or "bottom" strand), a scientist can’t tell if you have the "normal" version or the "mutant" version.

This is why doctors often roll their eyes at third-party health reports. If the software doesn't correctly align the strands to the reference genome, the entire health insight is garbage. It’s basically a coin flip.

How Labs Actually Handle the Strands

Genomics labs don't just guess. They use specific protocols.

  • Illumina Arrays: Most consumer kits use Illumina chips. These chips use a specific nomenclature called "Top/Bottom" or "Forward/Reverse."
  • dbSNP Database: This is the massive public archive of all known genetic variations. Scientists use this to sync their "this and that strands" to a universal standard.
  • Bioinformatics Pipelines: These are complex software stacks that "align" the raw bits of data to the reference genome.

If the alignment is off by even one base pair, or if the software assumes the wrong strand, the results change. In 2016, a study published in Nature highlighted how even professional researchers sometimes struggle with strand consistency when merging datasets from different studies. If the pros get it wrong, you can bet that a $20 "health uploader" website might get it wrong too.

Honestly, the whole system is held together by metadata. Without knowing the "build" of the genome (like Build 37 vs. Build 38) and the strand orientation, the letters A, C, T, and G are just alphabet soup.

Does This Affect Your Ancestry Results?

Mostly, no. But sometimes, yes.

Ancestry algorithms don't look at just one SNP. They look at "haplotypes"—long blocks of DNA that are inherited together. Because they are looking at thousands of points at once, a single strand flip doesn't usually derail the whole calculation. The algorithm can "see" the pattern.

However, when it comes to matching you with relatives (DNA matches), strand issues can matter. If two companies use different versions of this and that strands for their processing, comparing the raw data between them requires a lot of "cleaning."

This is why you can’t just upload your 23andMe data to every site and expect the exact same cousin matches. The way they interpret the "reverse" strand can lead to "false positive" matches where the software thinks you share a segment of DNA, but you actually don't. It’s just a mathematical glitch caused by orientation.

Decoding the Tech Speak

If you’re digging into this, you’ll see terms like "sense" and "antisense."

The sense strand is the "this" strand that has the same sequence as the mRNA (except with Uracil instead of Thymine). The antisense strand is the "that" strand—the template that the cellular machinery actually reads to build the mRNA.

Think of it like a stamp and an ink pad. The ink pad (antisense) is the reverse image, but it’s what you need to create the final print (the protein). If you try to read the stamp directly, everything is backward.

Practical Steps for Managing Your Genetic Data

If you’ve downloaded your raw data and want to actually use it without getting tripped up by strand issues, you need to be methodical. You can’t just trust a random PDF you found on a forum.

1. Check the Genome Build
Look at the header of your raw data file. It will usually say something like "Build 37" or "GRCh37." If you are uploading that data to a third-party tool, make sure the tool supports that specific build. If you upload Build 37 data to a tool expecting Build 38, the coordinates will be shifted, and the this and that strands will be completely misaligned.

2. Use Reputable Third-Party Tools
If you’re interested in health or traits, use tools that are transparent about their strand alignment. Sites like Promethease or Codegen.eu usually account for these flips, but they also provide warnings when a SNP is "ambiguous" (those A/T and C/G pairs we talked about).

3. Don't Self-Diagnose Based on One Letter
If you see a "scary" mutation in your raw data, check the orientation. Look up the RSID on a site like SNPedia. It will tell you the "standard" orientation. Compare that to your data. If your data says "CC" and the "bad" version is "GG," check if C and G are the "this and that" pair for that specific spot. You might actually be perfectly healthy and just looking at the mirror image.

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4. Verify with Clinical Labs
Consumer-grade DNA testing is for "educational purposes." If your raw data suggests a significant health risk, take that data to a genetic counselor. They will run a clinical-grade test (like Sanger sequencing) that doesn't rely on the same mass-market "chips" and is far more precise about strand orientation.

5. Keep Your Files Raw
Never edit your raw DNA text file. Even adding a space or changing a header can break the bioinformatics tools used to align the strands. Keep the original ZIP file exactly as you downloaded it from the testing company.

Understanding the relationship between this and that strands is essentially the difference between being a passive consumer and a literate user of your own genetic information. DNA isn't a flat book; it’s a three-dimensional molecule with a front, a back, and a specific direction. Once you realize that the "A" on one side is always a "T" on the other, the confusing world of genotypes starts to make a lot more sense.