SimBio Simulation Exercises - Sickle Cell Alleles Flashcards
How does Malaria occur?
People are infected when bitten by mosquitoes carrying certain kinds of protozoa. The malarial protozoa are released as the mosquito’s mouth parts pierce the skin of the unlucky victim. The protozoa then swim through the victim’s blood until reaching the liver. There they reproduce and emerge to infect the host’s red blood cells, after which another mosquito can suck them back up and start the cycle over again.
What is sickle-cell anemia?
Individuals with this disease have red blood cells that curve into a sickle shape instead of remaining in the circular doughnut shape of normal red blood cells. The sickle-shaped cells tend to get stuck in small blood vessels, blocking blood flow, and halting the supply of oxygen to downstream cells.
What is the cause of sickle-cell anemia?
It is genetic. Sickle-cell anemia is associated with a gene that encodes part of the hemoglobin molecule (called the Hb gene). Hemoglobin is the protein in red blood cells that carries oxygen. The allele for the normal hemoglobin protein is called HbA and the allele for sickle cell anemia is called HbS. People who inherit the HbS allele from both parents (i.e., have the “homozygous” genotype HbS/HbS) have a form of hemoglobin that makes their red blood cells highly prone to becoming sickle-shaped. People who inherit one sickle-cell and one normal hemoglobin allele (i.e., have the “heterozygous” genotype HbS/HbA) can experience health effects but often the effects are so minor that these people do not realize they carry the HbS allele.
How are sickle-cell anemia and malaria related?
Although the sickle-cell allele can cripple your red blood cells, it can also protect you against malaria. Having one copy of HbS (the sickle-cell allele) protects you from becoming sick from malaria. Heterozygous (HbS/HbA) red blood cells that become infected with the malaria protozoa will sickle. The body’s immune system recognizes that something is wrong with the sickled cells and disposes of them. So anyone who is heterozygous for the sickle-cell hemoglobin allele is protected from both malaria and sickle-cell anemia. In genetics lingo, this is an example of a case of “heterozygote advantage.”
Population Genetics
The study of how the genes in populations change over time.
Genes
Units of hereditary information composed of DNA (or sometimes RNA) sequences.
Loci
Genes are found on chromosomes. The place along the chromosome where the gene is located is called the locus (plural=loci). Population geneticists often refer to genes as “loci”.
Alleles
Alternate versions of genes.
They have different DNA sequences which may or may not code for different proteins.
Gene Pools
The total collection of genes in a population is called a gene pool. Population geneticists often focus on subsets of gene pools, such as all of the alleles at a particular locus.
The Hardy-Weinberg Equation
A formula that can be used for estimating allele frequencies from genotype frequencies or to estimate genotype frequencies from allele frequencies (for sexually-reproducing organisms).
The formula: p2 + 2pq + q2 = 1
It applies when there are two alleles of a gene.
The frequency of one allele is designated p and the other is designated q.
The first part of the equation (p2) gives the frequency of homozygotes of the first allele, the middle part (2pq) gives the frequency of heterozygotes, and the third part (q2) gives the frequency of homozygotes of the second allele (note: sometimes these are referred to as “Hardy-Weinberg proportions”).
If you know any one of the three parts, you can deduce the other two because p + q = 1 (and thus p = 1 - q and q = 1 - p).
For example, if you know the frequency of homozygotes for the first allele in a population (perhaps because all homozygotes for that allele have a distinctive trait), then you know p2. By taking the square root of that, you get p and by subtracting that value from 1 you get q. Once you know p and q, you can then plug those numbers into the Hardy-Weinberg equation to figure out the expected frequency of heterozygotes (2pq) and homozygotes for the second allele (q2).
Heterozygote
An individual with two different alleles of a gene.
Homozygote
An individual with two copies of the same allele.
What is Hardy-Weinberg equilibrium?
Hardy and Weinberg assumed that populations are very large and that there is no immigration or emigration. They also assumed that individuals mate at random to produce the next generation. Given these conditions, and no mutations or selection, there will be no evolution, and populations will be at what is known as “Hardy-Weinberg equilibrium”. The frequency of any allele in a population will be the same as the frequency of that allele in the haploid gametes (the eggs and sperm) and all that will happen from one generation to the next is that the alleles will be randomly shuffled and sorted again into pairs. Given this scenario, the probability of the various combinations of alleles (genotypes) will depend entirely on the allele frequencies.
What is the Hardy-Weinberg equation based on?
One way to think about the Hardy-Weinberg theorem and Hardy-Weinberg equilibrium is to imagine a system in which alleles (e.g., A and a) are drawn in pairs from a pot. The pot contains the same allele frequencies as were present in the previous generation. This pot automatically replaces what is drawn from it so that the allele frequency composition remains constant.
Applying probability theory, the chance of producing a genotype is the probability of drawing the first allele times the probability of drawing the second allele.
If we substitute in p for the frequency of A and q for the frequency of a, the probability of A/A will be (p)(p) = p2.
The probability of A/a will be (p)(q) and of a/A will be (q)(p) so the probability of a heterozygote (A/a or a/A) will be (p)(q)+ (q)(p) = 2pq.
The probability of a/a will be (q)(q) = q2.
The three probabilities must add up to 1 so p2 + 2pq + q2 = 1.
As the Hardy-Weinberg theorem applies to large, random-mating populations that do not experience mutation, migration, natural selection, or random genetic drift and many populations in the real world probably don’t conform to those rules, why is the Hardy-Weinberg theorem useful?
It allows us to quantify our expectations of what would happen in populations if evolution were not occurring, which allows us to compare those expectations to what we see in real populations.
For example, if we suspect natural selection is acting on a particular allele or genotype in a population, we can determine allele and/or genotype frequencies in the population in one generation and then see how well the frequencies conform with the expectations of Hardy-Weinberg equilibrium in future generations. If the frequencies are not very different than the expected Hardy-Weinberg proportions, that would be evidence that natural selection is not acting on that allele or that the selection pressure is too weak to detect with our data.
