Category Archives: Genetics

Human Genomes, For Cheap

Wired Science has a good post about Complete Genomics, a new company that promises to sequence an entire human genome for a mere $5000. This is approximately 5% of the current price tag.

You may have heard of companies, such as 23andMe, offering genomic sequencing for only a few hundred dollars. But these companies focus on specific single nucleotide polymorphisms, or SNPs, that represent a small fraction of the human genome.  They will sequence about half a milion base pairs, but Complete Genomics is hoping to sequence all 3 billion.

Wired explains how these developments could revolutionize biomedical genetics research:

And even at $5,000, the consequences would be enormous: Human genetic research, which is now focused on just a few genomic regions, and ignores types of variation that can’t easily be measured, would finally be able to assume its full form…

The cost and difficulty of sequencing genomes has forced medical geneticists to take a painstaking and limited approach to their work, necessarily looking only at a few genes or mutations. Even whole genome association studies — the gold standard of modern genetics — are misleadingly named: Geneticists search for similarities and differences between people at a handful of genomic locations that are most likely to vary between people, but still ignore most of the genome. Truly-named whole genome associations don’t yet exist.

If non-SNP variations can be correlated with human diseases, then inexepensive whole-genome sequencing could finally help realize the dream of personalized medicine. For now, Complete Genomics hopes to attract business from biomedical researchers. But eventually, the same technology might help ordinary consumers download their entire genome onto their personal computer. In case you’re wondering, you’ll only need about 750 megabytes of disk space.


The PCR Song


Pinker Doesn’t Care About Your Ancestry

Every once in a while, Harvard Psychology Professor Steven Pinker contributes his two cents in the pages of The New Republic. While most of these articles remain locked behind TNR‘s unfortunate subscription barrier, a recent article on geneology is open to the public with free registration.

Pinker is reacting to the burgeoning popularity of genotyping services that promise to reveal our ancestry and distant relatives. For example, this one promises to tell you if you are related to Marie Antoinette. The gist of his article: So What?

First Pinker exposes a common fallacy about ancestry that assumes we all have 4 grandparents, 8 great-grandparents, 16 great-great-grandparents and so on. If every position on our family tree was occupied by a unique individual, then this exponential function would predict that the earth’s population would have to be ~1,200,000,000,000,000,000,000,000 in the year 0 A.D. History teaches us that this was not the case, so we must conclude that incest was not the exception but the rule. Pinker refers to this conclusion as “pedigree collapse”:

The same arithmetic that makes an individual’s pedigree collapse onto itself also makes everyone’s pedigree collapse into everyone else’s. We are all related–not just in the obvious sense that we are all descended from the same population of the first humans, but also because everyone’s ancestors mated with everyone else’s at many points since that dawn of humanity. There aren’t enough ancestors to go around for everyone to have a family tree of his or her own. So it is a mathematical necessity, not a surprise, that genealogy will turn up strange bedfellows. George W. Bush is a distant cousin of his electoral opponents Al Gore and John Kerry (as well as of Richard Nixon, Ernest Hemingway, Queen Elizabeth, and, through her, every European monarch). Gore, for his part, is a descendant of Charlemagne, and Kerry is a descendant of Mary, Queen of Scots–and presumably also (thanks to his recently-discovered-to-be-Jewish paternal grandfather) of rabbis, cantors, and medieval moneylenders.

While the perception of kinship can have a major impact on how we relate to other people, Pinker wants to paint this preferential treatment as irrational–and in some cases–harmful. Often strong family ties weaken the strength of social institutions such as regional government. Pinker mentions this effect in reference to failed nation-building efforts in Iraq, where familial pedigrees remain relatively distinct thanks to the culturally-acceptable practice of marrying one’s cousins:

About half of all marriages are consanguineous (including that of Saddam Hussein, who filled many government positions with his relatives from Tikrit). The connection between Iraqis’ strong family ties and their tribalism, corruption, and lack of commitment to an overarching nation had long been noted by those familiar with the country. In 1931, King Faisal described his subjects as “devoid of any patriotic idea … connected by no common tie, giving ear to evil; prone to anarchy, and perpetually ready to rise against any government whatsoever.”

The implicit solution? Pass around a bottle of wine, turn up the Marvin Gaye and hope for some Sunni on Shiite love.

The Genetic Basis of Traumatic Memories

A new paper in Nature Neuroscience reveals the genetic basis for the ability to recall emotionally charged events. The gene in question is ADRA2B, which codes for the α2b-adranergic receptor. Quervain et al. found that Swiss subjects were better at recalling arousing images if they possessed a version of the receptor that lacked three amino acids. While the deletion variant significantly enhanced memories of emotional images, it did not effect arousal during the learning phase or memory of neutral images.

Additionally, Quervain et al. genotyped a cohort of Rwandan refugees. They found that subjects possessing the deletion variant were more likely to recall traumatic experiences than those with the full-length ADRA2B gene. It’s rare for scientists to go out of their way to demonstrate the real-world significance of their findings, so this approach should be applauded.

It’s tempting to speculate that the ADRA2B deletion variant could cause Post-Traumatic Stress Disorder (PTSD). However, the authors found no significant correlation between this diagnosis and subjects’ genotypes. More research is needed to clarify the connection, should it exist.

The findings are interesting in light of previous research into adrenergic signalling pathways. Propranolol, a drug that blocks beta-adregnergic receptors, has been shown to impair memory of emotionally charged events. Incidentally, the drug is also used to treat hypertension and essential tremor.

Research into the modulation of traumatic memories raises ethical questions. For instance, should the Army medicate soldiers with propranolol before they enter combat situations so they won’t suffer mental anguish later in life? While this could improve quality of life for veterans, traumatic stories play a crucial role in informing the public about the dangers of war. Though painful, such memories temper our violent and often self-destructive impulses.

Genetic Variation in Lab Mice

When designing an experiment, every scientist knows that it’s important to control for as many potentially confounding variables as possible.

Suppose you want to test the effects of a drug in a mouse model. In this case, you want to make sure that animals in the control groups receive equivalent treatment as animals in the test groups. For instance, if you deliver the drug by injection, then an equivalent saline injection should be administered to the control group. A carefully designed experiment allows you to pick up the subtle effects of your drug treatment.

But what if some variables are out of your control? A soon-to-be published article in Nature Genetics suggests that common laboratory mouse strains contain significant genetic variability. The authors performed a comprehensive analysis of mice at Jackson Laboratories, a major scientific supplier.

Genotype is a powerful modulator of drug response. For instance, one variant of a gene might code for an enzyme that metabolizes drug at a faster rate than the wild type enzyme. Unfortunately, this means that our hypothetical experiment could be confounded by uncontrolled genetic variability.

Coincidentally, this year happens to be the 50th anniversary of the field of pharmacogenetics (this is the first review). When the price of human genotyping drops sufficiently, this field could revolutionize the way doctors prescribe medicine. However, this kind of personalized medicine depends on basic research. For this research to mean anything, we need to be confident about the genotypes of our animal models.

Science Daily provides a nice summary of the research findings.