PERSONAL GENOMICS TURNS HEADS IN BIOTECH
23andMe, the Silicon Valley based personal genomics company named for the 23 pairs of chromosomes in a normal human cell, is turning a few heads in the biotechnology industry lately. After a very public and still unresolved dust-up with the FDA’s decision to halt marketing of the company’s DNA-based personal “health reports,” 23andMe is looking for additional ways to turn its vault of consumer DNA data into useful products in which the FDA will not interfere. They recently announced a partnership with Pfizer to pinpoint the genetic causes of inflammatory bowel disease (IDB). The hypothesis being tested: is 23andMe’s consumer DNA data large and accurate enough to characterize IBD disease states by a combination of genetic fingerprints rather than just symptoms?
23andMe is the highest profile consumer genetics company in the world and its foray into democratizing genomic data gives rise to bold new avenues for human health—faster drug discovery, efficient patient screening, and improved preventative medicine. For all these reasons, the technology behind 23andMe is well worth looking into.
A CHIP OFF THE NEW BLOCK
A tiny glass chip that is affixed with single strands of DNA is what a DNA chip, gene chip, or SNP chip is. These miniature transparent squares, called by many different names, make up the core of 23andMe’s technology.
While it does give a global look into an entire genome, gene chip technology is not the brute-force. Whole genome sequencing (WGS) treatment is usually reserved for simpler microbes and now humans, thanks to Illumina’s next generation sequencing (NGS) technology.
Gene chips take a look at our genome by finding the patterns inherent in DNA. They rely upon the very specific base-pairing rules followed by all double-stranded DNA molecules: A’s always pair with T’s; C’s always pair with G’s (adenine-thymine; cytosine-guanine). Each single stranded DNA on a chip can potentially represent one gene (or gene variant) within the human genome, even if the entire gene sequence is not present. Typically between 25 and 60 bases are used and high-powered software keeps track of the location of DNA sequences within the chip.
A researcher starts the process by collecting the patient sample (typically saliva) through a mail-in DNA kit:
- ISOLATE: extract DNA from the sample tissue.
- AMPLIFY: make copies of the specific gene or DNA sequences to be examined using the polymerase chain reaction (PCR).
- SORT AND LABEL: separate the sample DNA into single strands and label with a fluorescent probe.
- LINE UP: wash the labeled sample DNA onto the chip; The sample DNA sticks to (hybridizes) the DNA sequences on the chip if its bases are complementary.
- CLEAN AND RECORD: wash off the unbound sample DNA any sample DNA left is decoded.
- SOFTWARE SCAN: make correlations to a specific gene, or gene variant. Computer software keeps tabs on DNA positions and corresponding genes.
A DNA chip or SNP chip that is spotted with different variants of a particular gene is used to specifically determine genetic derivatives associated with a particular disease. DNA samples from patient groups, such as IBD patients, are compared with DNA samples from healthy individuals. The data is further analyzed to see if particular variants are more common in the patient vs. healthy population and vice versa.
FDA HITS PAUSE ON DTC GENETIC TESTING
The “direct to consumer” (DTC) genomics revolution that 23andMe purports to lead took a hit last year when the FDA ordered them to stop selling their personal health product to consumers.
The DNA chip technology behind their product is considered a reliable and accurate research tool by industry standards. What happened?
Well, it turns out that some SNP variants have a strong enough statistical association to be used as a diagnostic (for example, the BRCA1 mutation); however, not all SNP variants have this capacity, which in theory could lead to flocks of fazed consumers making faulty assumptions.
23andMe’s process involves SNP analysis on a cheek cell sample obtained from saliva provided by consumers through a mailed DNA kit. The analysis provides an estimate of an individual’s statistical risk based on a limited analysis of key genetic regions known to contain mutations associated with disease—like type 2 diabetes, age-related macular degeneration, and many more.
Even though 23andMe made it clear to consumers that their test results were not diagnoses but rather probabilities, the concern remained because those probabilities are based on a changing scientific understanding of the vast unknowns.
EASILY CONFUSED: SNP ANALYSIS AND SEQUENCING
The term “DNA sequencing” is often misconstrued with the term “SNP analysis” during discussions. DNA sequencing determines the order of every single base pair in a given gene (gene sequencing) or in an entire genome (whole genome sequencing). SNP analysis identifies single base differences between a given DNA sequence and a reference DNA sequence.
TERM OF THE WEEK: SINGLE NUCLEOTIDE POLYMORPHISM (SNP)
A single nucleotide polymorphism (SNP for short, pronounced like snip) is a one base difference in the DNA sequence of a gene when compared to the sequence found in the majority of the population. Many SNPs have no significant impact on an individual’s health, but others are associated with disease susceptibility.
Emily Burke, PhD has worked in biopharma for 20 years, gaining science writing experience at The Scripps Research Institute and Ionis Pharmaceuticals. As a Ph.D. molecular biologist, she is passionate about advancing the public’s understanding of science. In addition to being a self-proclaimed “science geek,” she is regularly asked to speak at international scientific meetings. When not teaching and writing the WEEKLY for Biotech Primer, Dr. Burke swims with her swim club and performs regularly on the improv circuit in San Diego.