I find that students tend to become catatonic and stressed out over population genetics, so we are NOT going to go there.

**Definitions**

**Population genetics**is the study of factors which affect inheritance patterns in populations of human beings.**Genotype frequency –**in the terms of a single locus, this measures the proportion of each genotype in a population. If we counted 100 people in a population, determined their genotype at a single autosomal dominant disease locus, and found that 40 were homozygous normal, 50 were heterozygous and 10 were homozygous diseased, then we would say that the genotype frequency:- for NN would be 40/100; (0.4)
- for Nd would be 50/100; (0.5)
- for dd would be and 10/100; (0.1)

**Allele frequency –**the proportion of chromosomes that have a specific allele. In the terms of the previous example, notice that we now have to consider that the 100 persons we were counting before have 200 chromosomes of the one we are discussing. Therefore, in counting the alleles:- the persons who are NN have two copies of the normal allele (there are 40 of those, so we multiply by 2 copies and get a value of 80 total N alleles here).
- the persons who are Nd have one N and one d, so there are 50 N alleles there.
- the persons who are dd have no copies of N, so nothing added there.
- If we now add up how many copies of allele N we have, the figure would be 80 + 50 divided by the 200 total chromosomes. That gives us 130/200 or 0.65 as the
**allele frequency of N.** - Since it must be true that all individuals have either N or d at this locus, a simple shortcut to find the allele frequency for the other allele d, is to simply subtract from 1.
- 1-0.65 gives us 0.35 as the
**allele frequency of d**.

**Deriving the equation**

A useful simplification which can virtually always be used to estimate an answer for your exam, is achieved by realizing that most disease alleles are rare in human populations. Therefore, the normal allele is much more common, and can be said to approximate 1. If we apply this simplification to the equation, then we can solve for 2Q as the approximation of the carrier rate in the place of 2PQ.

**Genotype and Allele Frequencies in Sex Chromosomes**

Since males are hemizygous for the X chromosome, remember that

Since males are hemizygous for the X chromosome, remember that

- the prevalence of affected males is Q
- the prevalence of affected females is Q2
- the prevalence of female carriers is 2Q

**New mutations**– The Hardy-Weinberg equation applies only to populations which are in equilibrium; mating without regard for selection of a partner depending on this allele. If a new mutation arises, the population may be in disequilibrium for that trait for a period of time.**Selection pressure**– if the individual with a genetic trait is at a selective advantage for breeding or survival, this alters the equilibrium state for that trait. There are many examples in human genetics of the selective advantage of a heterozygote:- falciparum malaria and sickle cell trait
- cholera and cystic fibrosis
- malaria and G6PD deficiency and
- iron deficient environments and hemochromatosis

**Genetic drift**– in small populations there may be significant deviation from Hardy-Weinberg equilibrium if an affected individual with a dominant trait enters the population (**Founder effect**) The larger the population, the less likely equilibrium will be profoundly affected.**Gene flow**– when populations become geographically close, they tend to develop similar gene frequencies. Think of this like diffusion of alleles in populations.**Consanguinity**– unions at the second cousin level or greater are considered consanguineous. Because descent from a common individual increases the likelihood that the same disease-causing genes will be shared, such unions will affect the equilibrium of that gene in the family. On average, siblings share ½ of their genes. First cousins share 1/8 of their genes. Second cousins share 1/32 of their genes.

1. 100 members of a population from Sub-Saharan Africa have been studied to determine whether they carry genes for sickle hemoglobin (HbS) or normal hemoglobin (HbA) using protein electrophoresis. The following genotypes were observed: HbA/HbA 85; HbA/HbS 12; HbS/HbS 3. What are the allele frequencies for HbA and HbS?

2. In the United States, approximately one of every 25 Caucasians is a carrier for cystic fibrosis. If two American Caucasians marry and have a child, what is the probability that the baby will develop cystic fibrosis?

3. The most common mutation associated with cystic fibrosis is ΔF508. If the prevalence of this mutation in a population is 1/60 and a man and woman from this population marry, what is the probability that their first child will be a son with cystic fibrosis?

4. A population in Iceland has a cystic fibrosis prevalence of 1/2500. What would be the predicted proportion of heterozygous carriers in this population?

5. One out of every 30 Ashkenazi Jews in Russia is a carrier of the ΔF508 mutation which is the most common cause of cystic fibrosis. What is the expected prevalence of cystic fibrosis in this population?

6. A 28-year-old man is a known carrier of an autosomal recessive mutation causing hyperprolinemia. It is known that 1/40,000 of the general population is homozygous for this mutation. If this man marries a woman from the general population, what is the probability that they will produce a child homozygous for the involved mutation?

7. The frequency of the most common C282Y mutation causing hemochromatosis in the U.S. is 5% (1/20). Assuming there are no other alleles which contribute to the incidence of hemochromatosis, what is the prevalence of homozygosity for the C282Y mutation in the U.S.?

8. In the United States, Alpha-1-antitrypsin deficiency is an autosomal recessive disorder that causes pulmonary emphysema in approximately 1 in 2500 Caucasians. What is the expected carrier frequency for this disease in the American population?

9. If the population incidence of a hemophilia A in males is 1/20,000, what would be the expected incidence of female carriers in the population?

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