Wednesday, December 22, 2010

Guest Post by The Epi Times: Oh, Baby! or Intro to Mendelian Genetics

I read a comment this morning on a blog that had me cringing at the lack of understanding of genetics. As parents, we need to work to be better informed in the basics of science, and we need to guard against the assumption that we understand something (this comment was offered with complete confidence but was woefully off the mark).

Reposted by permission. Please see the original at The Epi Times. Thank you for writing this! :-)


True story (maybe): I was working as a medical technologist, a lab boy, in a rather large hospital near the nation's capital. That night, I was working in the blood bank section, doing routine blood types and setting up blood for patients going to surgery the next day. I loved that job because, about every hour or so, I'd have to literally run to the emergency department to deliver O-negative blood for someone who had just been shot, stabbed, or been in a bad car accident. That allowed me to take in some of the adrenaline that late-night weekends brought with them. Oh, the stories I can tell you. Yet the one story that has stuck with me all that time is the interesting case of a child whose blood type made no sense when compared to the parents' blood types. It took five hours, lots of research, and one phone call to clear up the mystery. More on that case and an intro to Mendelian Genetics, as always, after the jump...

Their genes are varied, unique, but never "defective" or "faulty"

My wife was surprised to know that people in my extended family had blue or green eyes. She was even more surprised to know that there are plenty of Mexicans with blue eyes. Now, my wife is in no way someone that would stereotype on purpose, but it is a reasonable assumption that people from one country or region of the world outside the United States tend to be homogeneous (of one consistency) in skin, hair, and eye color. After all, you don't see a lot of short, black-skinned Germans, do you?
Uh... Well... Uh... Move on, nothing to see here...

There is a simple explanation as to why some of my cousins have blue eyes while I don't: GENETICS. Very simple genetics (so simple that they are taught in elementary schools nowadays) are often called Mendelian Genetics, named after Gregor Mendel. Mendel explained in the 1860s that seeds (peas) seemed to inherit their traits (color and texture) in a patter that could be statistically predicted. Of course, more and more people worked on this as the years went by, and we came to the understanding that there are two types of genes (alleles) that rule over inheritance patterns.

Dominant genes are those genes that code for something (eye color, skin color, height) regardless of their inheritance pattern. That is, they always "express" themselves. Brown eyes are coded for by a dominant gene. So it doesn't matter what my wife brings to the table (genetically speaking) with her beautiful hazel eyes. Our children have a very good chance of being brown eyed. Then again, there is a slight chance that they inherit blue eyes. Why? Because I might carry a recessive gene for blue eyes. (I haven't tested myself, nor do I need to.)

Recessive genes, on the other hand, code for something but are susceptible to being "covered" by dominant genes. So I might have a recessive blue eyes gene which is being covered by my brown eyes. My wife, on the other hand, has both recessive genes (one from each parent) for blue, hence the color of her eyes. There is a 1 in 2 chance that I'll pass on the recessive gene, while her chances of passing it on are even at 1:1 (since she has no dominant brown eyes gene or she'd have brown eyes, too). Our overall chance of having a brown-eyed baby (a latte baby, if you will) is 1 in 2 (because 0.5 chance of blue eyes multiplied by 1.0 chance of blue eyes is 0.5, or a 50% chance). If she had brown eyes too, then the chance of a brown-eyed baby would be 75% (1 in 3) because 0.5 multiplied by 0.5 is 0.25, or a 25% chance of a blue-eyed baby.

All we are saying is "give peas a chance"!

So, just like I can have a blue-eyed baby, my uncles and aunts had blue-eyed babies, my cousins. Those cousins can marry a brown-eyed person and have brown-eyed babies who, in turn, can later have blue-eyed babies, "skipping a generation." See? It's not that complicated, is it?

As you can see in the graphic above, yellow and green peas can "give birth" to white peas. Look closer, and you can see that their texture is different as well. Mendelian genetics is not a very hard concept is you just keep looking at what is dominant and what is recessive. In the graphic, green color (R) and a rough texture (Y) are dominant. So any combination of genes from both "parents" that have an R will be green, and Y will make them yellow. Lowercase "r" will mean yellow, and lowercase "y" will mean smooth IF AND ONLY IF there are no dominant genes to cover them.

In reality, there are a wide variety of genetic conditions that afflict many. They are rare, yes, but they are still important to look at. One condition that behaves very "Mendelian" is cystic fibrosis (CF). Cystic fibrosis is a condition where the lungs produce excess mucus, and they are not good at getting rid of that excess mucus. Folks with CF suffer from all sorts of lung infections because viruses and bacteria that get in there are difficult to clear out. The pancreas of a person with CF also produces a thick mucus that prevents the proper processing of food. As it turns out, a person with CF inherits two recessive genes for CF that cause the overproduction of that mucus. Someone who has only one recessive gene from one parent is okay (though they still have some slight problems). Those folks with the recessive genes grow up, get married, and the gene moves on down the lineage. Now, if two people meet and have a child, and they both have the recessive gene, then, like with blue eyes, there is a 25% chance that their child will have CF.

Other conditions that behave the same way are sickle cell disease and Tay Sachs disease. Together, they are called "Autosomal Recessive Disorders".

It is confusing and very frustrating to parents of children with autosomal recessive disorders that they gave birth to children with the disorder without any prior warning because they were healthy. If they were healthy, why would their children have such horrible conditions? Why didn't the gene "die out"? Well, it didn't die out because it's recessive, meaning that you need to be "unlucky" enough to have two people with one gene each get together in order to have a child with the disorder. Even then, it's only a 25% chance that the child will be full-on sick. There's a 25% chance that the child will have none of the recessive genes and only the dominant ones (in which case the genes do end there). But 25% and 25% do not make 100%. There is the remaining 50% chance that the child will also be a carrier of the gene, like the parents... And the gene lives on.

A 50-50 CHANCE

Of course, there are those conditions that are caused by dominant genes. In those cases, the affected people usually make it to adulthood. If they were to procreate with someone else who did not have the dominant gene, they would have a 50-50 shot of having an affected baby. The bright side there is the 50-50 chance of an unaffected baby. Huntington disease is such a dominant genetic disorder.
A very dangerous 50-50 shot...

So you can see from these examples that genetic conditions can't really be "washed away" from the population even if everyone was to be properly screened. The Nazis wanted to try this, and they failed miserably not only because of their misunderstanding of genetic conditions but because they were dealing with humans. No one is allowed to tell us who to love and when and how. No one is allowed to tell us whether or not to have children. Choice, it seems, is helping genetic conditions move on down our lineages. And that's not such a bad thing.

It's not a bad thing because genetic variations, even if they cause disease, allow for us to be varied and strong as a species. One of the first steps in evolution is mutation, so it's not all that bad that we have some folks with different genes. It may be a very difficult existence to live with a genetic condition, but it's just one of those things that make us human. It's not easy, but it is needed. I know, I know... Easier written than done. However, there is very real evidence that folks with sickle cell disease do not get infected with malaria since the malaria parasite cannot infect and reproduce in the sickle-like red blood cells of those folks. Even CF isbelieved to be a genetic adjustment to diarrhea-causing diseases like cholera.
Other genetic mutations just make you dress ridiculously

Of course, there are other ways in which genes can cause disorders to be passed down from one generation to the next, but I promised to keep this post simple and short(-ish).

Alright, so, where was I? Oh, yes... So I received cord blood for a blood type on a baby that was born late one night. The baby's blood type was O-negative. I'll spare you the genetics class and tell you that O-negative babies can only be born from a pair of "negative" parents. Type O can be inherited from parents who are both A, both B, one A one B, one A one O, one B one O, or both O. If one parent is AB, then the baby MUST be A or B, never O. Trust me on this one.

Guess what blood type the father was? That's right... AB-positive. The mother was O-negative. I had to do the blood type because the mother was a candidate for "rhogam", an infusion of antibodies designed to get prevent her from making antibodies against the Rh factor (positive/negative) of the baby if the baby is positive since the father was positive. So, to recap... Baby is O-negative. Mother is O-negative. But father is AB-positive. That is, the father had all three dominant genes (A, B, and Rh). The baby could only be A-positive/negative or B-positive/negative, nothing else!!!

I didn't know about the father until the obstetrician called me after I released the results of the baby's blood type. "Lab boy," she said, "I need you to retest the baby's blood."
"Why?" I asked.
"Because the father is AB-positive." If you could only see the expression in my face. The father had recently returned from overseas. He was in the military, and he had his blood type on his dogtags. Not only that, but he had been severely injured a few months back, so he knew for sure he had the right blood type on his tags. It was going to be a long night.

I spent the latter part of the night researching into whether or not the baby could be that blood type, given what we knew. I called the American Red Cross and spoke to some very experienced blood bankers. We all agreed that the Mendelian Genetics did not agree. There were only so many blood types the child could be. I read through several books on genetics and on blood inheritance. It appeared to me that a divorce was likely to happen. The obstetrician asked me to test and retest the blood. She even sent the father down to the blood bank to be tested. She then drew a sample from the mother for testing. It was all still the same, until...

If you can tell me what really happened without reading any further down, you get bonus points and maybe even some "mad props".
You're not my Dad... maybe!

Well, her name was not Watson, but what happened was quite elementary. I happened to notice that another cord blood was put in the sample case at around the same time as the child in question. Heck, I only noticed this because I had to re-test the cord blood so many times. So I took out that other sample and tested it. It was B-positive. This made me curious, so I called the obstetrician and asked if I could go up and draw blood from the child, based on my findings. She agreed, and I did. Indeed, the child's blood was B-positive. I called back and asked to speak to the nurse who collected the blood samples. She tearfully told me that she honestly did not know which sample was which since she had not labeled them at the bedside. Instead, she had waited until she got back to the nurses' station, with both samples in her pocket, and then decided to label them there. She was out of a job by the end of the night, from what I heard.
I hear she's doing well, though.

As I stated above, there are other genetic conditions/disorders that cause trouble and are inherited in different way that plain Mendelian patterns. They are many times unpredictable... and almost always heartbreaking. They are heartbreaking because you see a pair of parents and extended family who blame themselves for their child's condition. If something was wrong with my genes, I would also feel imperfect and thus guilty for my child's disease. Even now, in 2010, there are plenty of conditions which we are discovering to have a heavy genetic component to them.

In some cases, genes are necessary but not sufficient to cause a disorder. This may be the case with some conditions like autism or allergies. The other factor is somewhere in the environment. When the environmental factor works upon the defective gene, the disorder is manifested. ("Defective" is too strong a word. A gene is a gene is a gene, and we are no where near understanding the "why" these genes have come along in our evolution.) If you or someone you know is concerned about a genetic condition or about passing on a genetic condition to your children, please talk to a genetic counselor and your health care provider... And don't think for a minute that your genes somehow determine your worth. Like with everything else, it's what you do with those genes to the benefit of others that will be the true measure of who you are and how you will be remembered... how your legacy will live on.

1 comment:

Kim Wombles said...

This is such an excellent primer; I hope our blogging parents who get confused about the whole genetics argument will read this.



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