History Meets Genetics: Queen Victoria Edition
We’ve all heard of Queen Victoria. She was married to Prince Albert and they had a lot of children. Her children married into other royal families and essentially controlled the world. What does she have to do with genetics?
Ever heard of hemophilia? It’s a genetic bleeding disorder where your body can’t produce the necessary clotting factors to stop bleeding. There are different levels of severity of hemophilia, but it has the potential to be very harmful to one’s health.
The disease is a recessive x-linked disease. The “recessive” part means you need two alleles of a gene to express the disease and be symptomatic. The “x-linked” part means the gene that codes for hemophilia is on the X chromosome and is passed down from the mother.
Let’s talk about some genetics terminology:
genotype: alleles of a gene (Ex: hair color; D= dominant, d= recessive)
phenotype: this is what you see (Ex: hair color; dominant = brown, recessive = blonde)
homozygous: both alleles are the same (Ex: DD or dd)
heterozygous: different alleles of a gene (Ex: Dd)
Genetics is all about inheritance. You have two copies of alleles in a gene. One allele is inherited from each parent.
If this makes sense, then perfect! Where genetics can become confusing is with the type of inheritance pattern.
We’ll talk about complete dominance because that’s arguably the simplest and easiest inheritance pattern to understand.
What is complete dominance?
It means that your dominant allele fully masks the expression of your recessive allele. You only need 1 copy of the dominant allele for the dominant trait to be expressed.
You need 2 copies of the recessive allele for the recessive trait to be expressed.
A great example of this is eye color. Brown eyes are dominant to blue eyes. If a female has brown eyes and she has children with a man who has blue eyes, their children will either all have brown eyes or half will have brown eyes and half will have blue eyes.
Why is there a discrepancy? Since the brown eye allele is completely dominant, we don’t know based on the information above if the female is homozygous dominant or heterozygous. If you take a genetics class, your professor will have to specify if the individual is a heterozygote or homozygote.
Example:
Type of heritability pattern: Complete dominance for hair color
D = dominant allele for brown hair
d = recessive allele for blonde hair
You get one allele from each parent
You only need at least one copy of the dominant allele to have full expression (Ex: Dd, DD = dominant trait; brown hair)
You need two copies of your recessive allele to show expression (Ex: dd = recessive trait; blonde hair)
Question: You cross a blonde haired person with a heterozygote. What is your F1 generation phenotype and genotype?
blonde haired person: recessive trait = dd
the blonde haired person has 1 type of allele (d)
heterozygote: brown hair, dominant trait = Dd
the heterozygote has 2 types of alleles (D and d)
We need to multiply the blonde haired person’s alleles by the heterozygote’s alleles
d x D and d x d = Dd and dd for the genotypes
Our genotypic ratio is: 2 Dd to 2 dd since the blonde haired person has two copies of the d allele
Our phenotypic ratio is: 2 brown to 2 blonde
And that’s it!
Back to Queen Victoria. She was a carrier of hemophilia, which means she was heterozygous for hemophilia. She had an X chromosome with a normal gene that expressed the correct clotting factors (proteins). She had another X chromosome with a mutant gene that could not express the correct clotting factors (proteins). This is where genetics becomes a little more complex.
Hemophilia is a recessive genetic disease. The tricky part is that males have 1 X chromosome. If a male inherits the mutant gene on the X chromosome, he will have hemophilia because he doesn’t have another X chromosome to offset the mutated gene and make clotting factors.
Females have 2 X chromosomes and their fully functioning normal X chromosome can offset the effects of the mutated gene on the other X chromosome.
You may wonder: Does this mean no females will have hemophilia if they are a heterozygote?
Not quite.
There’s a phenomenon that occurs in females called X inactivation. Females have 1 extra X chromosome in comparison to males and this can pose a problem because if both X chromosomes in a female are expressed, the gene expression becomes unbalanced.
To circumvent this issue, X inactivation occurs where one X chromosome in a female essentially gets turned off so that the genes on that chromosome cannot be expressed. However, that inactivated chromosome still gets replicated during reproduction. How does this happen? We have to think back to general biology.
Central Dogma:
DNA —> RNA —> protein
Do you remember transcription and translation?
Transcription is basically looking at the DNA and copying the gene of interest.
Translation is converting the copied gene of interest into a protein and that is how you get gene expression.
You can think of it like cooking. Let’s say you want to use a recipe to make chicken pot pie
“DNA"” is the recipe that you read. You read the recipe and gather the ingredients needed to make the delicious chicken pot pie.
“RNA” is the equivalent of you cutting up the chicken, putting together the pie crust, and making the filling.
“Protein” is the equivalent of the chicken pot pie after you take it out of the oven and it’s ready to be inhaled.
Certain genes are highly transcribed, meaning your body is constantly making proteins that are from that gene.
Some genes aren’t transcribed because they’re not accessible due to epigenetic modification like methylation that causes the DNA to be tightly condensed. When this happens, the enzymes involved in transcription physically cannot access the genes.
This is what happens with X inactivation. The DNA on the X chromosome becomes so tightly packed that the enzymes involved in transcription cannot access the DNA on the X chromosome to read it.
If you have a female who is a heterozygote for the mutant hemophilia gene, there’s a chance that she could develop symptoms of hemophilia. The inactivation is random and the normal or the mutant X chromosome can be turned off. The remaining X chromosome that does not get inactivated has genes that are expressed.
Queen Victoria was asymptomatic because her other X chromosome could offset the effects of hemophilia.
Since Queen Victoria and Prince Albert had many children, some of their sons developed hemophilia and some of their daughters were carriers. When their daughters married into German and Russian families, the mutant gene for hemophilia was passed down to multiple generations.
When you think of genetics, it can be daunting and overwhelming.
The key to understanding genetics is probability. If you can understand probability, genetics will be a piece of cake.
So what is probability? Probability goes back to your favorite Algebra II class from high school. Probability relies on statistics and how likely it is for an outcome to happen. Thankfully, genetics relies on a very basic version of probability.
Probability in its simplest form follows the following formula:
# of possible desired outcomes / # of total outcomes
Where genetics can become tricky is with variable expressivity, penetrance, dominant diseases, and pedigrees. We’ll talk about all of this later. For now, rest assured you can understand the basics of genetics and ace your class!
