Genetics Primer, 1: Variations on Mendel

If you ever took basic biology in school, you may remember the eye-color meme as an example of Mendelian genetics. Remember we have two copies of each of our genes, one from Mom, and one from Dad. The eye-color example is the one where they tell you that if you get at least one "B" gene from Mom OR Dad, you will have brown eyes (BB or Bb) but if you get the "b" version from both parents (bb) you will have blue eyes. Thus, blue eyed children can have brown eyed parents only if the parents are both carriers of the blue gene. In genetics, blue is recessive. So we all come away from this thinking that eye color is a simple Mendelian trait and is absolutely determined by the B/b versions we inherit.

BUT some people may remember that for this to work the teacher had to ignore the green eyed kids, or the hazel eyed kids. And occasionally there was a brown eyed kid who swore that both Mom and Dad have blue eyes, which the teacher skirted past very quickly (because she probably remembered that non-paternity rates in the US is as high as 10%, but that's not the only possibility). The fact is that there are multiple genes controlling eye color (hence the green and hazel eyes) and to strictly focus only on the B/b gene and the blue/brown binary is to ignore a lot of normal variation.

The simplification worked in the classroom only because variation in the other genes is more uncommon, especially in an ethnically uniform population, so teacher may have a fighting chance that a group of kids will fit the simple paradigm without having to invoke to greater complexity that actually exists. (Aside; the Mendelian inheritance is correct; it's how those genes are "read" into traits, or "phenotypes", that gets complicated.)

Even if you have blue eyes, there are variants from dull grey to brilliant blue, indicating that other factors affect the exact color formed. One complication is that there may be more than two versions of the gene (called "alleles"); not just B/b, but B1, B2, B3..... b1,b2 b3..... Even if any ONE person can have at most two versions of the gene, within the population there may be more. (I may be b1b2for example, and you may be b4b4, though we both have "blue" eyes). These different alleles are not present in equal numbers and may vary enormously in frequency; for example, in the population, b4 may be very common, and b2 may be extremely rare. And these may also change what we see in the person's traits.

Different genes can interact with each other and modify each other too. So, there may be other genes that affect only blue versus grey in the "bb" folks. And the green-eyed gene which we will call G is only visible if you have the blue eyed gene too (bb), if you have Brown (BB or Bb) then it doesn't matter what was at the green G/g site, it's masked. Just to complicate things further, you may have the gene for a particular color, but it may not be expressed for other reasons. Some of these reasons are genetic: for example, if you lack the gene to deposit thepigment in the proper place, it doesn't matter if you make the pigment. So people with BB or Bb alleles may not be brown eyed, due to other genes. And, some of these reasons are not strictly genetic, in the sense of being DNA-coded, such as epigenetic modification, variable penetrance, and variable expressivity--although they are often heritable. I'll discuss this later.

Depending on the trait (not just eye color), variation may be also be affected by the environment (for example the presence of particular chemicals in the diet), and some variation may simply occur by chance.

We tend to dislike this last explanation, because we like things to be determinate: black OR white (or blue OR brown); we don't like the idea that a random event (what the geneticists call "stochastic") can occur, and we don't like shades of gray. But chance also plays a part.

So, even for a trait as seemingly simple as eye color, we have already quite a lot of complication:

• Multiple genes
• Multiple versions of each gene (e,g, b1,b2, b3.....b(n))
• Interactions between genes
• Non-genetic changes (epigenetics, penetrance, expressivity)
• Random variation
• Environmental influence

Indeed the only deterministic thing we can say is that a bb child will not have brown eyes--- although I'm not sure even that is always true. The rest is up for grabs.

To read this entire series in order, visit the Genetics Page.