Which Grandparent Are You Most Related to?

Illustration by Robert Neubecker

What makes you who you are genetically? The easy answer is your family. The longer answer begins with the fact that all humans have two parents (at least for now), and usually four distinct grandparents (there are unfortunate exceptions). Genetically you are a recombination of four separate individuals. But that does not mean you have an equal contribution from four separate individuals. Humans normally carry 23 pairs of chromosomes: 22 autosomal pairs and one pair of sex chromosomes, either two copies of the X for a female or an X and a Y in the case of males. By Mendel’s law of segregation you receive one copy of each pair from your mother (via the egg), and one copy from your father (via the sperm). This means exactly half of your genome derives from each parent.

Things begin to get more complicated going back two generations. One might think that of the 44 autosomal chromosomes you would receive 11 from each of the four grandparents. (For simplicity we’ll leave the sex chromosomes out for now. If you are a female, you receive one X from each parent, while if you are a male you receive an X from your mother and a Y from your father, who got it from his father.) But while the proportion of one’s inheritance from parents is fixed by exact necessity, the fraction from grandparents is governed by chance. For each of the chromosomes you inherit from a given parent, you have a 50 percent chance of gaining a copy from your grandfather and a 50 percent chance of gaining a copy from your grandmother. The laws of independent probability imply that there is a 1 in 4 million chance that all of your maternal or paternal chromosomes could come from just one grandparent!* What’s more, genetic recombination means that chromosomes aren’t purely from one grandparent or the other; during the cell divisions that produce sperm and eggs, chromosomes exchange segments and become hybrids. You almost certainly have different genetic contributions from your four grandparents.

But this is not just abstract theorizing. Imagine that you could know that 22 percent of the genome of your child derives from your mother, and 28 percent from your father. Also imagine that you know that 23 percent of the genome of your child derives from your partner’s mother, and 27 percent derives from your partner’s father. And you could know exactly how closely your child is related to each of its uncles and aunts. This isn’t imaginary science fiction, it is science fact.

Last year, I sent a sample of my then 2-month-old daughter’s genetic material to the firm 23andMe and received her results. As it happens I already had the genotype of my daughter’s mother, father, all her uncles and aunts, and all four of her grandparents. In other words, her full pedigree was already available when her results came back, and she was easily slotted into the bigger genomic family photo album. Not only do I know which proportions of her ancestry derived from each grandparent, I know which regions of her genome derive from each of her grandparents. For example, one grandmother is half Norwegian, so genealogically my daughter is^{one-eighth Norwegian. But I quickly calculated using diverse data sets of various nationalities that genomically she is somewhat more than one-eighth Norwegian. This is reasonable as 28 percent of her ancestry, according to how her DNA analysis matches up with the DNA of the rest of the family, happens to come from her half Norwegian grandmother.}

One might think these sorts of facts are useful only for the sake of satisfying curiosity, but sometimes theoretical knowledge can be put to practical use. Last spring my wife asked our pediatrician about testing my daughter for a treatable autosomal dominant condition which I happen to exhibit. The physician’s reaction was straightforwardly paternalistic. She would not authorize the test because she believed our daughter was too young. This did not sit well with my wife. The mutated gene which causes my condition has been well characterized. My wife went home and quickly used one of 23andMe’s features to find out if my daughter inherited a copy of the gene through me from my mother or my father. My mother is affected by the same ailment as I am, while my father is not. The happy ending is that my daughter almost certainly does not have the condition, because she inherited that genetic region from my father. The bigger moral of the story is that decentralized genetic information can allow persistence to pay off.

All of this is a consequence of the fact that I have an obsession with genetics. But it is also contingent on the fact that for less than $500, you can send in a kit and receive back a record of 1 million genetic variants in short order. This would have been unfathomable just 10 years ago. Out of 3 billion base pairs in the entire human genome, 1 million may not seem like much, but the ones tested were chosen because they vary across the population, and they represent a substantial proportion of the variable genome. Much of the information is banal, trivial, and redundant. My eyes are dark brown, and those of my wife are blue. Therefore, you will not be surprised to learn that a quick check on variants that code for eye color predicts that my daughter will shake out to have a light brown shade (as a matter of fact her eyes are light brown or hazel).

Source: http://www.slate.com/articles/health_and_science/human_genome/2013/10/analyze_your_child_s_dna_which_grandparents_are_most_genetically_related.html
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