Because men are much less efficient at passing genes on then women are, personal genomics could get complicated

geneaologyby Carasova.net

The inferred distribution of grandparental contribution
[Via Gene Expression]

In my write up on variation in inheritance patterns for Slate last week I did not explore the likely quantitative distribution in any detail (frankly, I think that part is confused or muddled at best). My primary focus though was on the empirical reality of variation, which people utilizing personal genomic services will receive, perhaps to their surprise. But in part triggered by that Slate piece and follow-up discussions at Twitter with Michael Eisen, Graham Coop decided to crunch the numbers. More concretely he took the known patterns of recombination in the human genome (from a paper he co-authored, Broad-Scale Recombination Patterns Underlying Proper Disjunction in Humans), and input these values into a simulation which generated distributions of contribution from maternal and paternal grandparents, How much of your genome do you inherit from a particular grandparent?

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Perhaps it would have been better to use maternal lines of descent rather than paternal.  Women more faithfully transmit the genetic heritage of their ancestors than men do.

The genes I carry are much more likely to make it beyond the second generation if I only had girls.

Real life is much more complex than we think. It turns out that there is a reasonable chance that you could be the grandchild of someone yet carry little of their DNA on your chromosome. At least along the paternal line.

We normally expect 25% of your chromosomes to come from each grandparent. You get 50% from each of your paents and they got 50% from each of their parents.

In real life, this can vary quite a lot, especially since men are actually less proficient in carrying out a very basic biological process. Instead of 25%, it is possible that only 10% made it.

There is a lot of math involved if you go back and read the original posts. I’ll try an walk you through this.

I get half my genes from my father and half from my mother. So, my son should get 50% of my genes (the other 50% coming from his mother) or 25% from each grandparent, right?

It turns out it is more complicated than that. There is a process called recombination that acts to scramble up chromosomes.  So my sperm do not contain perfect copies of my parent’s chromosomes but mixed up ones containing bits of both,  looking like a patchwork of their genes.

Here is what it can end up looking like in three generations, looking at a single chromosome.

Each person in the first generation has two copies of a chromosome – call it chromosome 1. Recombination mixes this up and then the mixture gets passed on to me.  You can see that my wife and i each again two copies of chromosome 1, with 50% of  the chromosomal sequences derived from each of our parent. Just mixed up.

There is then again recombination here to produce the third generation, my son.

recombiation

Gets pretty scrambled? Remember this is just a example.

So, in the third generation we see that one chromosome of the pair is Yellow, Blue and Green. Thus parts of the DNA from both grandparents made it into the genome of the grandchild. But The Yellow/Blue grandparent provides well over 25% of the chromosome. Well over 60% of that chromosome that makes it into the grandchild comes from just one grandparent.

And this illustration also shows what might happen if no recombination occurred (the Red/Light Purple copy).  In this case, none of the Brown/Purple grandparent made it at all to the grandchild.

In this example, genes from only 3 grandparents made it to the grandchild. And the actual percentage of each grandparent is much different than the 25% we were taught in school. Instead of the 25:25:25:25 ratio expected we get 0:50:67:33.

Now, when this is averaged out over 22 chromosomes (we don’t count the sex chromosomes for obvious reasons), these numbers balance out. Sure Chromosome 1 may not have any of one grandparent, but other chromosomes may make up the difference.

What does it look like when we average this over all the chromosomes, using real data on recombination?

Those are the histograms shown at the top. These look at the fraction of, say, my parent’s DNA I will pass onto my son. And the fractions of my wife’s parents DNA she will pass onto my son.

We can see that for my wife, the chances are greatest that the DNA she passes onto our son will  come equally from both of her parents (the 0.5 on the chart). That is, it is most likely that 50% of the DNA she passes on will come from her mother and 50% will come from her father.

The chances that 40% will come from one and 60% from the other are much smaller for her, but it is still possible. But it is very unlikely that she will pass on less than 40% of one of her parent’s and 60% of the other.

Women do a pretty good job, then, passing on the genes of their parents in pretty equal amounts.

Not so with men. Men’s recombination rates are lower than women. Thus they scramble their chromosomes less than women. When you lower recombination rates,  there is a greater likelihood that some DNA will not get passed down, just as we saw with the example.

In fact, it is more likely that my sperm split my parent’s DNA 60:40 rather than 50:50. ANd which is the 60 and which is the 40 is determined purely by chance.

One in 200 sperm I produce may have less than 20% of genetic material from  one of my parent and 80% coming from the other. That means that my son, when we add in his mother’s DNA, might have very little of the genes from one of my parents. Instead of 25% perhaps less than 10%.

This could get complicated with things like 23andMe. It is possible that comparing the genomes of a grandparent and a grandchild may only find 10% similarity rather than the expected 25%.

This is as expected and does not mean any funny business happened.Nothing to see here.

However, it does mean  that if I had a daughter, it is much likely that she will be a more faithful vessel for her grandparents genetic heritage. Sure I could take the chance that my son would pass down 40% of the genetic material I passed to him. But he might only pass 10%.

Would you like to take that chance?

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