Population Genetics & Risk

Just take the square root of the incidence.

For autosomal recessive disorders the frequency of the diseased allele in the population is typically very low so how would we calculate the frequency of this disease causing allele from the incidence?

Because it is an autosomal recessive disorder: Incidence = 2pq + q^2 but because homozygous mutation is commonly fatal and this is relatively low in the population and p ≈ 1: Incidence = 2q or q = 1/2 x Incidence

How do we calculate allele frequency in autosomal dominant disorders from the incidence?

The heterozygous genotype of both of these alleles helps to provide a protection against malaria so natural selection has actually increased the amount of diseased allele in the population because of heterozygote advantage.

Natural selection can help to reduce the amount of mutant alleles in a population. Why then is there a higher prevalence of sickle cell anemia and β-thalassemia in populations?

Two ways: [(64x2)+32]/200 = 160/200 = 0.8 for M or The square root of 0.64 = 0.8 The same would be done for the frequency of allele N.

The following population information has been given for a certain gene. How do we calculate the frequency of allele M in the population and the frequency of allele N in the population.

1/2500 (this is easy because this is the incidence) q = √(1/2500) = 1/50 (this is the frequency of allele q) Because p is almost equal to 1 we will calculate the frequency of heterozygotes as 2q or: 2 x (1/50) = 1/25 Two heterozygotes would have a 1/4 chance of having a child with CF so: 1/25 x 1/25 x 1/4 = 1/2500

The incidence of cystic fibrosis is 1/2500 among European populations. What is the chance that two two heterozygous parents would meet and have a child with cystic fibrosis? Do the math.

q = 1/10,000 in males. In females 2pq = 2 x 1 x 1/10,000 = 1/5,000

The incidence of hemophilia A is 1/10,000. What is the mutant allele frequency in males? What is the frequency of carrier females in the population?

1/1600 1/20 = 2pq (p ≈ 1) so 1/20 = 2q or q = 1/40 Incidence = (1/40) x (1/40) = 1/1600

The probability of being a carrier for a diseased allele for PKU in a specific population is 1/20. What is the estimated disease incidence in this population?

Genetic drift can cause the fixation or extinguishing of an allele from a population. Low number populations typically extinguish an allele (the recessive one) whereas high number populations typically fix allele frequencies.

What are the effects of genetic drift on low and high number populations?

1. Random mating 2. No migration into or out of the population 3. No new mutations 4. A large population

What four assumptions must be made for a population to follow Hardy-Weinberg equilibrium?

1. Caucasians 2. African Americans 3. Mediterraneans 4. Caucasions 5. Ashkenazi Jews

What group is at highest risk of developing the following diseases? 1. Hemochromatosis 2. Sickle cell disease 3. α & β-thalassaemia 4. Cystic fibrosis 5. Tay-Sachs Disease

Reduced fitness is the reduced ability of an individual in a population to reproduce which you would think would lead to loss of the mutant alleles but a balance between new mutations and reduced fitness maintain mutant gene frequencies in a population.

What is reduced fitness? Why does this not lead to the complete loss of mutant alleles?

It is the ability of an individual in a population to pass on the diseased alleles to offspring based on the disease traits. For example, patients with CF are commonly diagnosed and have serious symptoms prior to reaching reproductive age so the reproductive fitness is low to 0. Huntington disease on the other hand commonly does not occur until later in life and as a result has a high reproductive fitness as patients who are diagnosed have likely already reproduced.

What is reproductive fitness? Describe discussing cystic fibrosis and Huntington disease.

(p^2) + 2pq + (q^2) = 1 p = the frequency of the commonly found functional allele (M) q = frequency of diseased allele (N) p^2 = the percent of homozygous MM in population 2pq = the percent of heterozygous MN in population q^2 = the percent of homozygous NN in the population

What is the Hardy-Weinberg Equation and what do each of the variables stand for?

The movement of a person with a recessive allele into a small population that causes a large spike in mutant allele frequency in the population.

What is the founder effect?

The frequency of all alleles for a gene must add up to 1. 1 - 0.6 = 0.4 RR: 0.6 x 0.6 = 0.36 SS: 0.4 x 0.4 = 0.16 RS: 2 x 0.6 x 0.4 = 0.48

While studying gene RMT you discover there are two alleles for this gene R & S. You find that the frequency of allele R in the population is 0.6. What is the frequency of allele S and why? How many people in the population are homozygous RR? Homozygous SS? Heterozygous RS?

Because if there are diseased alleles in the family it is likely that it is present in many members of the family making it more likely than the general population that the disease will occur.

Why does consanguinity lead to high prevalence of disease?