In 2003, successful whole human genome sequencing was announced by the Human Genome Project and Celera Genomics, however the sequence was actually 15% incomplete. Researchers solved some of the puzzle, but from 2013-2021, our reference model of the human genome lacked 8% of the full sequence.
On May 27, 2021, an international collaboration of researchers announced they have filled most of those gaps, identifying about 115 new genes that code for proteins. This was made possible because Pacific BioSciences created new technology which scans 20,000 DNA letters at a time compared to conventional technology which scans a few hundred. There is remaining work to scan the Y chromosome.
So how can whole genome sequencing be of benefit for you?
Preventative, personalized, precision medicine (3P-M) starts with whole genome sequencing (WGS). 3P-M requires what is called multi-omic biological analysis, where the data sets are multiple “omes” such as your genome, proteome, transcriptome, epigenome, and microbiome. By combining information from your omes, researchers can identify potential therapeutic targets (biomarkers) to prevent disease and keep you healthy.
An Invitae proactive genetic testing study of over 1800 people found that 16.5% of healthy people have clinically actionable results, predominantly in genes for cardiovascular disease and cancer. Diagnostic results from Human Longevity’s 100+ Health Nucleus program identified a similar rate of near-term actionable results.
It is useful to set your health baseline by measuring the current state of your DNA so you can detect how it changes over time. How should you do that? Who are the providers? What are the costs? Are they worthwhile to pay for personally? What are the potential risks of getting your whole genome sequenced?
First, The Sequencing Terminology
A quick explanation of the terms.
Genotyping is the least expensive DNA service. Your genes are compared to a standard “reference genome” to identify single-nucleotide polymorphisms (SNPs), variations of a single letter (base pair) of DNA. There are over 660 million SNPs in the reference human genome (out of 3.05 billion letters of DNA), which makes them the most common type of genetic variation in humans. They can explain traits such as eye color and inherited diseases such as cystic fibrosis and sickle cell anemia, as well as act as markers indicating a risk of developing complex common diseases like diabetes and Alzheimer’s disease.
Exome sequencing will find medical insights and many other things about you that genotyping does not. It decodes the stretches of your DNA (exons) that provide instructions for making functioning proteins — about 20,000 genes and 1 percent of your genome. This method allows variations in the protein-coding region of any gene to be identified, rather than in only a select few genes. Because most known mutations that cause disease occur in exons, whole exome sequencing is an efficient method to identify possible disease-causing mutations.
Whole genome sequencing is the most thorough. In theory, it translates every letter in your genome. In practice, some regions that are difficult to sequence get skipped, so sequencing is usually done 20 or even 50 or 100 times to catch errors. That’s known as 20x, 50x, or 100x “coverage.” There is still an 8% full sequence gap in most results.
Genome Sequencing Providers
Although there are a plethora of inexpensive ($59-$99) direct to consumer DNA testing services such as 23andMe, Ancestry.com, LivingDNA, FamilyTree, and MyHeritage, they only screen for a small number of select biomarkers. In return, they own your DNA data and often sell it for commercial use. You, and your current and future relatives, don’t want that, especially because they can be compelled by law to provide your DNA to see if it matches that found at crime scenes which could implicate you, your kin, or your relatives. In short, current privacy laws do not provide enough protection.
If you are going to get sequenced, private complete sequencing from reputable firms who do not sell your information is better. Prices continue to drop and eventually may be free according to Andrew Hessel, the co-founder of Humane Genomics and Chair of the Board of Genome-Project-Write.
- Dante Labs ($599)
- Full Genomes ($1150) 30x sequencing plus Y chromosome.
- Invitae — Provide cancer and cardio risk screening of 147 genes for $350. Working with Pacific Biosciences to create WGS tests.
- Nebula Genomics 30x Whole Genome Sequencing ($299) with privacy protection accessible only by you.
- SelfDecode — ($90) — limited scan of 500 biomarkers; In progress of launching SelfDecode 2.0 (also $90) covering 35 million SNPs.
- Sequencing ($399) with privacy protection
- Veritas — tests must be ordered by your physician. Cost unknown.
WGS results will be 8% incomplete until these providers are using advanced Pacific Biosciences or similar technology.
Leading Sequencing Technology Platforms
- 10X Genomics — determine gene expression within cells and populations of cells.
- GeneDx, owned by OPKO Health, handles the majority of WGS clinical sequencing for physicians.
- Illumina’s NovaSeq 6000 provides WGS. NextSeq 1000 and 2000 focus on exome and transcriptome sequencing.
- Oxford Nanopore Technologies — minION portable DNA tests.
- Pacific Biosciences HiFI Sequel Systems — near-complete WGS using long-read technology including laser scans of 25,000 letters at a time.
- Thermo-Fisher Scientific’s Ion Torrent — whole genome, exome and transcriptome sequencing.
How to Use Your Whole Genome Sequencing Results
Your actual DNA readout comes in various formats. A sequencing machine produces a FASTQ file, with long strings of letters. Those fragments are then reassembled into a SAM (Sequence Alignment/Map) or BAM (Binary Alignment/Map) file which can then be sent to various DNA-analysis services. These service providers then send you a variant call format (VCF) file to compare your DNA against a reference genome to highlight what’s unique. They can also send a text file that lists hundreds of thousands of variations and their locations in the genome. Since huge text files aren’t comprehensible, software is necessary to help interpret your data and inform you on what is meaningful and actionable.
- Technonomy Guide to Genetic Testing — I got my genetic results. Now what?
- GeneCards — searchable library of everything known about each human gene. See this example.
- MyGeneRank — app to assess risk of polygenic events.
- GenBank — GenBank ® is the NIH genetic sequence database, an annotated collection of all publicly available DNA sequences available to the scientific community.
- Nebula Genome Exploration Tools — included with Nebula’s Deep and Ultra-Deep sequencing offerings.
- Sequencing.com’s Genome Explorer — website to upload your genome and analyze it.
- SelfDecode ($97 / year, $297 lifetime) — independent biohacker website to upload your genome and analyze it. See this review which includes a 15% discount code.
Interesting Longevity Gene Research
Here are some additional interesting articles on the latest in longevity gene research.
- Longevity Genes Project
- Seek to identify protective genes in centenarians
- Run by Nir Barzilai at the Albert Einstein College of Medicine
- Longevity biomarkers
- Determined from studies of mice
- GENtervention Database — Visual results with links to GeneCards
- Dialing down grim reaper gene (Insulin-Growth-Factor 1)
- Gene for healthy aging in worms (and potentially humans)
- Atum Biosciences — designing and manufacturing synthetic new genes and proteins for research. GeneDesigner 2.0 is their free online tool, combined with Gene Atlas for exploration.
- Risks of uncontrolled gene editing
Thanks for reading. As your reward for focusing on your health, here’s another amazing update on the progress of DNA research. In February of 2021, researchers announced that they had found and sequenced the DNA from a million-year old steppe mammoth! For comparison, the oldest sequenced human DNA is from a mere 430,000 years ago. If you are intrigued about the potential to recreate mammoths in the modern world, check out Beth Shapiro’s 2015 fascinating book, How to Clone a Mammoth: The Science of De-Extinction.