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by gravelc
3362 days ago
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I agree with this to a point. Obviously, genetic information can be quite informative for non-complex traits or diseases caused by variants in only 1 or a few genes. The reality is the genome isn't the complete instruction set for what makes you you. The interaction with the environment dataset is missing, along with any heritable epigenetic information. Add to that, our understanding of function is still extremely limited. We still don't really understand how one gene generates different proteins (via alternative splicing) at different rates. Or how gene expression is so finely regulated at a cell-specific and sub-tissue-specific level. The list goes on. Rules that seem to apply to one gene or gene family don't apply to others. One day, we'll likely get there, but that day is still some way off. For that reason, I see no great reason to have my genome sequenced at the moment, though it'd be reasonably trivial to do so. |
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And (unfortunately) those are the exact variants that services like 23andme do not detect.
23andme uses an array chip. These only detect common variants, in locations that have been pre-planned while designing the chip. A batch of patient samples are all tested together, and the probe for each variant produces a signal. Software then tries to cluster samples into three groups, which are homozygous normal, heterozygous, and homozygous abnormal. If the variant isn't common, then there would not be a decent number of samples in each group, and the clustering would fail. These tests are literally incapable of detecting any variant that is rare.
To detect rare variants, you need to do proper sequencing, for example with Sanger (single gene), or high throughput sequencing (AKA NGS, Next Generation Sequencing). This can be targeted panels of selected genes, whole exome sequencing, or whole genome sequencing.
A disease caused by a variant in a single gene (a monogenic disease) is usually caused by a rare variant. The more severe the disease, the more rare the variant is. A gene may have loads of common variants that do not cause disease. A gene may have a really rare variant that does not cause disease. Or it may have a rare variant that does cause disease - but this needs to be determined by someone with training and experience in the field.
As a lab, we regularly get inquiries by people saying "I have a variant detected by 23andme in <known disease gene> - could this be causing my <rare genetic condition>?" The answer is "No - this test is incapable of detecting disease-causing variants - it only detects the benign ones."