Cystic fibrosis carrier status, and what your raw DNA file can honestly tell you
Cystic fibrosis is the condition people most often go looking for in their raw DNA data, and it is also the one where the gap between what a consumer file contains and what a carrier test actually does is widest. This page is about that gap.
Also known as: CF, CFTR carrier, mucoviscidosis.
- Gene
- CFTR
- Inheritance
- Autosomal recessive
- Carrier frequency
- about 1 in 25 in people of Northern European ancestry, with different rates in other backgrounds
What it is
Cystic fibrosis is caused by changes in CFTR, a gene whose protein moves chloride across cell membranes. When both copies carry a disease-causing change, the salt and water balance at those surfaces goes wrong and secretions in the lungs, pancreas and gut become thick. It is a recessive condition, so carrying one changed copy causes none of this. One working copy of CFTR does the job.
The reason CFTR comes up so often is arithmetic. Around one in twenty-five people of Northern European ancestry carries a pathogenic CFTR change, which makes it one of the most common recessive carrier states in that population, and the condition itself is serious enough that carrier testing is offered routinely before or during pregnancy.
How it is inherited
Recessive inheritance is worth being precise about, because the numbers are easy to misread. If one parent is a carrier and the other is not, no child can have cystic fibrosis, though each child has a one in two chance of being a carrier. If both parents are carriers, each pregnancy carries a one in four chance of a child with the condition, a one in two chance of a carrier, and a one in four chance of neither. Those odds reset with every pregnancy. They are not a sequence, and three unaffected children do not make the fourth more likely to be affected.
This is why a carrier result is a fact about a couple rather than about a person. On its own it changes nothing about your health. It becomes actionable only alongside a reproductive partner's result, which is the reason the sensible next step after any carrier finding is testing the partner rather than testing yourself again.
What your raw DNA file can and cannot tell you
A chip file cannot answer this question. A 23andMe, AncestryDNA or MyHeritage export is a genotyping array: it reports the bases at a fixed list of positions chosen in advance, and it is blind to everything else. CFTR has well over a thousand known pathogenic variants spread across the gene, so a handful of typed positions cannot establish that the rest of it is clear. Aimosti does not report carrier status from a chip file at all, and says so rather than returning a reassuring blank.
A whole-genome VCF or gVCF is a different matter, and it is what our carrier module reads. It can find pathogenic CFTR changes anywhere the sequencing covered, which is far more than a panel of common variants. What it still cannot do is prove a negative. Large deletions such as the common CFTRdele2,3 are copy-number changes that a short-variant VCF does not represent, and the poly-T and TG tract in intron 9 that modifies how some variants behave is not something we call. So a file with no CFTR finding lowers the odds that you are a carrier. It does not take them to zero, and we do not describe it as if it did.
It is also worth being plain about what this product is not. Clinical carrier screening is a defined thing with a defined minimum, and it includes conditions our panel deliberately leaves out because a standard variant file cannot call them, spinal muscular atrophy and alpha thalassemia among them. A re-analysis of a file you already own is a way to look at data you paid for once. It is not a substitute for carrier screening ordered by a clinician, and if you are making a decision about a pregnancy, the clinical test is the one that should carry the weight.
A genotyping chip reads only a few hundred thousand pre-selected positions, about 0.02% of your genome, chosen for common variation. It does not sequence the rest, so it cannot find the rare or novel pathogenic variants the clinical and carrier modules look for: a “no finding” from chip data means “this chip never looked”, far more so than with whole-genome sequencing. Chip data suits common-variant traits, pharmacogenomic tag SNPs, and haplogroup ancestry, not clinical or carrier screening.
Common questions
Can I check my cystic fibrosis carrier status from 23andMe or AncestryDNA data?
Not reliably, and Aimosti will not pretend otherwise. Those files are genotyping arrays that read a fixed set of positions, while CFTR carries over a thousand known pathogenic variants. A chip can tell you about a specific variant it happens to type, and nothing about the rest of the gene. We do not report carrier status from chip files.
My whole-genome file shows no CFTR variant. Am I definitely not a carrier?
No. A clear result lowers the odds considerably, but a short-variant VCF does not capture large deletions in CFTR, and there is always residual risk after any negative carrier result, including a clinical one. If the answer matters for a pregnancy, ask for a clinical carrier test rather than relying on this.
I am a carrier. What does that mean for my health?
Nothing, in the ordinary case. Carriers have one working copy of CFTR and do not develop cystic fibrosis. The finding matters for family planning, which is why the useful next step is testing a reproductive partner rather than investigating yourself further.
Both my partner and I are carriers. What now?
This is the situation where a genetic counselor is genuinely useful, and where a result from a re-analysis should be confirmed with a validated clinical test before anything is decided. Each pregnancy would carry a one in four chance of an affected child, and there are established options to discuss. That conversation is outside what a report can give you.