Genetic Counseling

To learn about the field of genetic counseling, I went through the various problems here. Although I tend to prefer finding more creative ways of going about this, this time, I think I'll simply answer the questions given on the site itself.

First off: here's the pedigree described in the story:

(I apologize for the spots that are somewhat confusing. Progeny has some design problems that I eventually became tired of circumventing.)

Part II--Autosomal Dominant Traits

1. Do autosomal dominant disorders skip generations?

No. Simply because, by definition, they are dominant, then if their presence in the genotype will be reflected in the phenotype.

2.  Could Greg or his mother be carriers of the gene that causes myotonic dystrophy?

Because myotonic dystrophy is an autosomal dominant disorder, Greg or his mother could not be carriers of the gene that causes it. If they had the gene, they would suffer from the disease.

3. Is there a possibility that Greg’s aunt or uncle is homozygous for the myotonic dystrophy (MD) gene?

There is no possibility that Greg's family members are homozygous for the MD gene because one of their parents did not have the MD gene. Because they did not have it, they could not pass it on.

4. Symptoms of myotonic dystrophy sometimes don’t show up until after age fifty. What is the possibility that Greg’s cousin has inherited the MD gene?

There is a fifty percent chance that his cousin has the MD gene, because the cousin's mother was heterozygous (her father did not suffer) and the father does not have the gene. A Punnett square for this situation reveals a fifty percent chance of inheriting the MD gene.

5. What is the possibility that Greg and Olga’s children could inherit the MD gene?

There is no possibility of Greg and Olga's children having MD. Because their parents did not have the gene, they cannot have the gene themselves. Therefore, their children cannot get the gene from them.

Part III--Autosomal Recessive Traits

1.  What are the hallmarks of an autosomal recessive trait?

An autosomal recessive trait can skip generations, but requires two copies of the mutant gene to be apparent.

2.  What does consanguineous mean? Why is this concept especially important when discussing recessive genetic disorders?

If two people are said to be consanguineous, that means that they are descended from a common ancestor. This is important in recessive traits because if two people are consanguineous, then they often have somewhat similar genotypes--including recessive genes.

3.  What is it about the inheritance pattern of factor VIII deficiency seen in Greg and Olga’s pedigree that point toward it not being an autosomal recessive trait?

Looking at Greg and Olga's pedigree, we can see that it appears mainly in boys and only rarely is apparent. This would point towards this disorder being an X-linked gene.

Part IV--Sex-Linked Inheritance

1. What are the characteristics of X-linked recessive inheritance?

X-linked recessive inheritance is typically primarily apparent in boys because males only have one copy of the X-chromosome. This means that mutations on this chromosome are typically masked in girls by a good copy of the X-chromosome.

2.  Why does a son never inherit his father’s defective X chromosome?

A son cannot inherit his father's X chromosome because he always receives the Y chromosome from his father. This is what makes him a son and not a daughter.

3.  What is required for a woman to display a sex-linked recessive trait?

For a woman to display an X-linked recessive trait, she would need two mutant copies of the X-chromsome--one from both parents.

4.  Return to the pedigree drawn earlier for Greg and Olga; mark those persons who are carriers of the factor VIII deficiency gene.

On Greg's side of the family, his mother and maternal grandmother are carriers. On Olga's side, her maternal grandmother and her mother are carriers--and potentially, her.

5.  What is the chance that Olga carries the gene for factor VIII deficiency? Calculate the probability that she will pass it to her offspring. Will male children be affected in a different way than female children?

There is a  1/4 chance that Olga has this gene, and a 1/4 chance that she will pass this gene to her children. If she does, there is a 1/8 chance that the child will suffer from the disease (if male) and a 1/8 chance that the child will be a carrier.

6. What is the chance that Greg carries the factor VIII gene? Can he pass the gene on to his sons? His daughters? How will each be affected?

Because the factor VIII gene is on the X chromosome and he is not a sufferer, there is no chance that he has the gene. He cannot pass the gene on to his sons, because he will give a Y chromosome to them. He will give an X chromosome to his daughters, but the mutant gene will not be on it.

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I will stop here--this one's already gone on long enough, especially for one as mundane as this one. I will probably include the rest of the tutorial in a Part II, which should be up within a few days.

Dominance: Why?

As I was reflecting over the last week, I realized that, although I've heard quite a bit over my life about the dominance of alleles, I'd never heard a real explanation of why certain traits express themselves over others. So...I found out.

On this page, Stanford University scientist Ruth Tennen answers this question. Apparently, there are several different reasons this happens. The most basic one occurs when the gene's function is to make a protein. If the recessive allele does not make this protein, then because the other allele will anyway, its presence is apparent in the phenotype.

For example, consider red hair. Because the protein that the MCR1 gene makes removes red pigment, as long as a person has one working copy of the MCR1 gene, they will not have red hair. A person has to have two copies of the broken MCR1 gene in order to have red hair.

Then, believe it or not, the opposite can be true--the dominant allele can be the broken gene. This was somewhat confusing at first to me, so I'll do the best job I can to explain it, often by stealing the metaphors used on the aforementioned site.

This situation of the recessive allele being the functional gene often occurs when the broken protein made by the dominant allele gets in the way of the protein made by the recessive allele. Consider a relay team. The first runner on the relay does his job just fine--he runs his 100m. But the next runner always drops the baton on the handoff, and because of this, this relay never wins. The first runner here is like the functional protein made by the recessive allele--it does its job just fine. But then, because the broken protein can't help out along the way, it is the work of the broken protein--the dominant allele--that is expressed.

Now, of course, there are more situations than this. There's codominance and incomplete dominance and...well, you get the idea. However, the basic idea here is that it's all about the proteins and the way they get along.

See you soon! 

Are We There Yet? (The Joy of Maps)

Before I go into too much depth, I'll give credit where credit is due.

We've recently been studying the madness of chromosome mapping over the past few days, so I thought I'd give a quick overview. So...here we go!

Chromosomes can be viewed as similar to a thumb. A thumb has two separate regions, split by a knuckle, one of which is clearly longer than the middle. Similarly, a chromosome has two arms, a p arm (shorter) and a q arm (longer). These arms are split by a notch known as the centromere.

Bizarre analogies aside, let's take some time to look at a specific gene on the X chromosome: Xq28.

Let's look at what each subset of this cytogenetic locus means:

X

This simply means that this particular gene (MRX28) is located on the X chromosome (more on the significance of this later!).

q

This means that the gene is on the longer of the two arms of the chromosome--the q arm.

28

This means that this gene is on the band labeled 28. Chromosomes, when stained, show different bands. This is caused by the differing ways in which the DNA is wrapped.

Now, I chose a gene on the X chromosome for a reason. Genes on this particular chromosome are known as "x-linked." Abnormalities on the X chromosome are always apparent in males because there is not a dominant allele on the X chromosome to mask the presence of the mutant allele. For an example of this, consider color blindness. Men are color blind for red and green more often than women because the gene(s?) for detecting red and green light is on the X chromosome, and men only have one copy of the X chromosome, so defections are not masked.

The MRX28 gene I mentioned earlier is one that has been linked to mental retardation. Here are some examples of other x-linked genes and the symptoms mutations carry:

COL4A5 (Xq22)

This is the gene that causes Alport's syndrome. This syndrome damages the various blood passages within the kidneys, which leads to urine in the blood and less effective filtering by the kidneys.

ATP7A (Xq21.1)

This particular gene causes Menkes syndrome, in which the body cannot absorb enough copper. This can affect the structure of many organs within the body (including skin, hair, and nerves) and often leads to a low body temperature and bleeding in the brain.

MECP2 (Xq28)

This gene is the root of Rett syndrome. This is usually found in girls because, although a defective X chromosome can make it to a boy, the boy will not survive. A girl, however, because she has two X chromosomes, is typically strong enough to live with the syndrome. Symptoms of Retts include problems breathing, seizures, and loss of sleep.

On a slightly cheerier note, I would like to relate an accomplishment of mine that is directly related to this. While I was having my hair cut, I made a joke about already going bald. The lady cutting my hair then asked if my mother's father was bald. Although my mother was adopted, I began to realize something: the gene that causes baldness is probably on the X chromosome. (I haven't actually researched this, but it seems likely.) This would also explain why women tend not to go bald--women have two X chromosomes, so they would not suffer the symptoms of a defective X chromosome as often.

Is that right? 

Eugenics

Well, I've thrown together an extremely (for me) short prezi on the origins and impacts of eugenics.

I also really recommend the Eugenics Archive, which was also extremely influential in the development of this post.

Have fun!

Eugenics: Based on "Fact" on Prezi