Personal Genome Testing

Dr. Rosie Redfield

Special Series: You & Your Genome

Spit Tests

By David Kattenburg

Rosie Redfield spat in a tube and mailed it to a Mountain View, California outfit called 23andMe. A month later, the University of British Columbia geneticist and MOOC instructor received a nuanced assessment of her potential susceptibility to a variety of genetically-linked disorders (she had to log onto the web to read it).

A genetics researcher and educator herself, Rosie Redfield was glad she had her spit tested, and encourages others to do the same, if they are so inclined. Listen here:


Their choice will be more limited than Redfield’s, though. Late last November, the US Food and Drug Administration (FDA) ordered the Google-affiliated genetic testing service to stop marketing the US$99 spit test Rosie Redfield had done, until it can prove its results are worth more than … a vial of wet spit.

The injunction only pertains to the disease susceptibility segment of its test. 23andMe continues to offer direct-to-consumer (DTC) genotype testing for genealogical purposes.

Should DTC genetic testing for potential disease genes be regulated, because people might commit rash acts when told they’re (supposedly) carrying a rogue gene of some sort? Should personal genotype testing fall under the purview of consumer protection agencies? Should DTC genotype test marketers be subject to government regulation?

Answering these questions hinges on an understanding of what genetic susceptibility is all about.

The ability to determine or deduce a person’s genetic susceptibility to disease has been made possible by the discovery of discrete DNA variants within the human genome called single nucleotide polymorphisms — SNPs (pronouced snips) for short. This discovery, in turn, has been made possible by relentless advances in rapid (“high-throughput”) genome sequencing technologies.

DNA, the universal genetic source code, is a double-helical polymer of building blocks called nucleotides, strung together in structures called chromosomes. Humans have 23 pairs of these chromosomes (i.e. 46 in total; our diploid number), one of each pair from mum, the other from dad. Each nucleotide contains one of four different nitrogenous bases — adenine (A), thymine (T), guanine (G) and cytosine (C) — arranged in complementary base pairs. The diploid genome is six billion base-pairs long.

Most of the six billion base pairs making up the human genetic code are exactly the same from person to person. But at about one in a thousand positions, there’s a slight difference: an A has been substituted for a G (or vice versa), or a T for a C.

This is a single nucleotide polymorphism. An estimated twenty million SNPs exist in the human genome — human genetic variability accumulated over 150,000 years of modern human evolution.

From the get-go, researchers realized that SNPs could act as signposts for disease-causing genes — genes a few hundred or thousand base pairs away from a given “Tag SNP.”

To understand how so, one must understand the mechanics of a phenomenon called “crossing over,” when each of the 23 chromosome pairs in a primordial sex cell engages in a delicate shuffling, or recombination, prior to becoming a sperm or egg.

Think of a deck of cards, where the Queen of Hearts and Ace of Spades have been placed next to each other. In an average act of shuffling, those two cards will tend to stay close to each other, if not together. Gene linkage is kind of the same.

Armed with a complete SNP map — and the ability to sequence people’s genomes at lightning speed — researchers could scan the SNP catalog of large numbers of people suffering from a disease like Crohn’s, say, searching for SNPs they all have in common, but that are absent from healthy control populations. In this case, one could conclude that that SNP is very close to the Crohn’s “gene,” and narrow down the search for the actual culprit gene or control segment accordingly.

Genome-wide association studies, as these are called, have opened the door to personalized risk assessment and drug therapy. At the same time, it didn’t take entrepreneurial researchers, bioinformaticians and social networking gurus long to come up with the idea of marketing genotype testing to the general public.

The problem is that genetic susceptibility to a disorder may be associated with not one, but a whole bunch of protein-producing genes, as well as genetic control elements that switch these genes on or off, or regulate their expression in some other fashion. The likelihood of developing such a disorder would depend on how many genetic risk elements a person has inherited, ranging from no risk at all, to great certainty. Assigning percentages to these risks — values that can actually be interpreted and assessed — is highly complex.

Then there are the environmental factors that determine how one or a handful of disease-associated genes end up getting expressed: a person’s overall health status, the vices they engage in, the food they eat.

Rosie Redfield acknowledges the interpretative uncertainties of DTC genotyping in this audio story, as she brushes off the potentially troubling news she received from 23andMe. Anyone less knowledgeable could be excused for gulping and gasping as they stare at their online genetic profile.

The fact that most people’s doctors haven’t the genetics knowledge to offer intelligent counseling doesn’t make the DTC genotyping conundrum easier.

With the medical component of 23andMe’s spit testing service shut down, personal genomics aficionados can still shell out their hard-earned cash to have their Neanderthal content assayed, or the migration routes their ancestors trudged millions of years ago mapped out. Listen to Winnipegger Darrell Cole describe his experience with National Geographic’s Genographic Project (“The Greatest Journey Ever Told”).


Dr. Jim Rupert
Dr. Jim Rupert

And listen to UBC sports geneticist Jim Rupert, who got himself tested for a sports endurance gene — and turned out to be positive. He isn’t headed for the Olympics.

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