Which Grandparent Is Your Child Most Related to? They Aren’t Equal.

What Have We Learned?
Oct. 18 2013 10:31 AM

Which Grandparent Are You Most Related to?

Your family tree says you inherited 25 percent of your ancestry from each. Genetics says you didn’t.

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Other results are more relevant. I am a “PTC nontaster.” This means that I lack the ability to perceive a particular chemical called phenylthiocarbamide, which is often applied to paper one can touch to the tongue in high school biology classes to illustrate genetic inheritance of recessive traits. My wife has a copy of the tasting variant, as well as the nontasting one. (Her father, a notoriously finicky eater, has two copies of the tasting variant, and so he is a “super-taster.”) In real world terms it means that my wife has a greater sensitivity to bitter foods than I do, something I can attest to as a real phenomenon. For me, salad dressing is optional. There are studies which suggest that small children who are tasters tend to be fussy eaters, as opposed to those who are nontasters. You can guess which result I was rooting for. And in this case the die landed exactly as I would have preferred:  My daughter is a nontaster, just like her father!

At this point you may wonder if my daughter’s future, in my mind, is predicted down to minute details by the character of her genotype. No. The reality is that most heritable traits are difficult to predict from specific genes because they are influenced by so many genes. (This is why I was so interested in which grandparents she received more of her genes from overall, by the way.)  When it comes to individual prediction, most of the strongly predictive genes influence traits we already can see with our eyes. (My daughter will have wet earwax!) But even facts which might seem silly can loom large for grandparents. To my mother’s chagrin, my father is quite proud of his disproportionate contribution to his granddaughter. Similarly, it is clear my mother-in-law has no complaints about being overrepresented in the genetic constitution of her first grandchild.

But the story does not end here. Let’s shift from science fact to science fiction. A survey of 1 million variants of a 2-month-old are to a great extent for entertainment purposes only, as the promotional material for 23andMe cautions. But in the very near future, parents will be able to avail themselves of precise and accurate genomes of their future child in utero. Potential sperm donor clients will be able to simulate thousands of potential offspring outcomes from different male contributors. Currently, only primitive assays are available in utero, such as whether your child has a chromosomal abnormality which might indicate Down syndrome. But imagine a scenario in which parents are given a summary from their genetic analyst of their future child at the sixth week of pregnancy. That summary will include superficial characteristics, perhaps even predictions of facial morphology. But it will also have a number that indicates mutational load for large-impact genes. This number will vary from fetus to fetus. Mutation is after all somewhat random.  

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The implications are obvious. Go with a child with a higher mutational load than you prefer? Or try again? This will be especially important for the children of older fathers, who are already contributing more than their share to the mutations in their offspring. Accuracy is of the essence for what comes next. The personal genetics tests available today look for common variations within the population. One of the possible “killer apps” of genomics in the near future may be to assess the regions of the genome where an individual has unique mutations, ones that differ from the parents’ DNA. These variants are informative in a way that family history simply can’t be. 

When it comes to personal genomics, we currently live in the age of the hobbyist. There are a plethora of websites that can do genealogical analysis for you if you don’t have computational skills. Off the shelf applications give you updates on the latest research on a particular variant of personal interest. I hope in the near future I can install a smartphone app that feeds me a stream of actionable results. Personal genomics is truly leveraged once you integrate it holistically into the quantified-self framework. Not only would you know the genome you were born with, but you could have hourly updates on biomarker results, as well your continuous pace of physical activity. Disease risk in many cases is a combination of both genes and environment, and integrating information from both domains opens up many possibilities. Naturally there are people in Silicon Valley working on projects which aim to take this framework to the mass market.

The goal here is not to foresee my daughter’s destiny, it is to understand it and shape it so that she can flourish. I take a mild interest in my own genomics, but I am surprised at how much more interested I am in my daughter’s results. For her the future will be. Much of my future has been determined by choices made in the pre-genomic era. By the time she is entering elementary school I expect to have a full and accurate copy of her whole genome. At that point we’ll start a new discussion about who she is, and who she wants to be. I’m a geneticist, not a developmental psychologist, so this is going to be an experiment where I am totally at a loss for forecasting the outcome. But someone has to step out of the cave of personal genomic ignorance first, and see if the coast is clear.

*Correction, Oct. 18, 2013: This article originaly misstated the odds that the chromosomes from one parent could come entirely from just one grandparent. There is a 1 in 4 million chance of this happening.

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