Lab- Population Genetics:

Background:

Population Geneticsexamines genetics at a population (rather than individual or family) level.The field focuses on the frequency and distribution of specific alleles of a gene over a large, randomly breeding group of individuals (plants or animals). Every population can be genetically defined by its gene pool, that is, by the sum of all alleles in the breeding members of that population at a given time. Population geneticists characterize this gene pool through the calculation of allele frequencies and genotypic frequencies.

Allele frequencyis the proportion of a certain ALLELE among all allele copies present in the population in question.

Genotype frequencyis the proportion of a certain GENOTYPE in the population, in relation to all genotypes present.

These two calculations are central to population genetics and are intrinsically related to one of the most famous principles that describe the flow of genetic information in a population: the Hardy-Weinberg law.

The Hardy-Weinberg lawstates that gene and genotype frequencies in a population will remain in equilibrium (unchanged from generation to generation) in an infinitely large population in the absence of mutation, migration, selection, and nonrandom mating - in other wordsin the absence of evolutionary forces.

IF genetic variation remains constant across generations, i.e. evolution does not occur, the genotypic distribution in the progeny is determined solely by the allele frequency in the parents.

Consider gene A.A encodes a protein that acts in a specific cellular process and is found in most humans as either form "A" or form "a".These two alleles may differ from each other at a single bp (A has a guanosine; a has a cytosine) and the proteins may be distinct at only a single amino acid (A has a Leu amino acid; a has a Phe).The two proteins have different enzymatic activity that leads to a small phenotypic change, but without any real cost to organism health or fertility.

If A and a are the primary alleles found in a population, we can predict the occurrence of each, and the same frequencies hold true through the generations, provided no external forces disturb the balance.If the frequency of any one of the possible genotypes is known (i.e. A/a or a/a or A/A), then the frequencies of the remaining genotypes can be mathematically calculated.In addition, if a population is in Hardy-Weinberg equilibrium, phenotype frequencies and genotype frequencies can be interconverted.Finally, the Hardy-Weinberg principle allows for the quantitative analysis of evolutionary forces that change allele frequencies.

principle:let p = frequency of one form of allele (A)

let q = frequency of other form of allele (a)

If these alleles are the two major alleles, then p + q = 1

(1 = 100%, or all of the possible outcomes)

Therefore:p2= AA (likelihood of having one A * one A)

q2= aa

2pq = Aa

p2+2pq + q2= 1

Example for alleles A and a in humans when frequency of A = a:

Sperm

A= 0.5a= 0.5

FemaleA =0.5A/A = 0.25A/a = 0.25

Gametes:a=0.5A/a = 0.25a/a = 0.25

Phenotypes:p2+2pq + q2= 1 0.25 + 0.50 + 0.25 = 1

Alleles:p = q = square root of 0.25 = 0.5

However, most populations do not have two alleles that are found at equal frequency.

EXAMPLES

Example 1: the MN human blood type

Humans inherit either the M or the N antigen. The MN blood group system is under the control of an autosomal locus found on chromosome 4, withLMandLNalleles. The blood type is due to a glycoprotein on the surface of red blood cells. Phenotypic expression is codominant because an individual may exhibit either or both forms of the glycoproteins.

If we let the frequency of allele M=p and the frequency of allele N=q, then the genotypes will be

• Frequency of MM genotype = p2
• Frequency of MN genotype = 2pq
• Frequency of NN genotype = q2

We can take a sample of the population and count the number of people with each genotype.For example, consider a sample of 2400 from Suburbia, USA, has:

• 730 individuals of type MM, or 30.42%
• 1225 of type MN, or 51.04%
• 445 of type NN, or 18.54%

Apply the Hardy-Weinberg equation (p2+ 2pq + q2= 1) to calculate the allele frequencies.There are several ways to accomplish this, such as:

• Frequency of M: p2+ 0.5 (2pq) = 0.3042 + (0.5 x 0.5104) = 0.559

1. Note: you have to use of the 2pq number because only half of the heterozygous alleles are M.The other half are N.

• Frequency of N: q = 1 - p = 1 - 0.559 = 0.441

With the allele frequencies in hand, we can apply the HW equation once more and calculate the expected genotype frequencies for a different population. For example, Metropolis, population 155,000:

• MM: p2= (0.559)2= 0.312, or 48,434 individuals
• MN: 2pq = 2 x 0.559 x 0.441 = 0.493, or 76,421 individuals
• NN = q2= (0.441)2= 0.194, or 30,145 individuals

However, what we know is that frequencies of the two alleles vary widely among human populations:

Example 1: the MN human blood type

Humans inherit either the M or the N antigen. The MN blood group system is under the control of an autosomal locus found on chromosome 4, withLMandLNalleles. The blood type is due to a glycoprotein on the surface of red blood cells. Phenotypic expression is codominant because an individual may exhibit either or both forms of the glycoproteins.

If we let the frequency of allele M=p and the frequency of allele N=q, then the genotypes will be

• Frequency of MM genotype = p2
• Frequency of MN genotype = 2pq
• Frequency of NN genotype = q2

We can take a sample of the population and count the number of people with each genotype.For example, consider a sample of 2400 from Suburbia, USA, has:

• 730 individuals of type MM, or 30.42%
• 1225 of type MN, or 51.04%
• 445 of type NN, or 18.54%

Apply the Hardy-Weinberg equation (p2+ 2pq + q2= 1) to calculate the allele frequencies.There are several ways to accomplish this, such as:

• Frequency of M: p2+ 0.5 (2pq) = 0.3042 + (0.5 x 0.5104) = 0.559

1. Note: you have to use of the 2pq number because only half of the heterozygous alleles are M.The other half are N.

• Frequency of N: q = 1 - p = 1 - 0.559 = 0.441

With the allele frequencies in hand, we can apply the HW equation once more and calculate the expected genotype frequencies for a different population. For example, Metropolis, population 155,000:

• MM: p2= (0.559)2= 0.312, or 48,434 individuals
• MN: 2pq = 2 x 0.559 x 0.441 = 0.493, or 76,421 individuals
• NN = q2= (0.441)2= 0.194, or 30,145 individuals

However, what we know is that frequencies of the two alleles vary widely among human populations:

Example 1: the MN human blood type

Humans inherit either the M or the N antigen. The MN blood group system is under the control of an autosomal locus found on chromosome 4, withLMandLNalleles. The blood type is due to a glycoprotein on the surface of red blood cells. Phenotypic expression is codominant because an individual may exhibit either or both forms of the glycoproteins.

If we let the frequency of allele M=p and the frequency of allele N=q, then the genotypes will be

• Frequency of MM genotype = p2
• Frequency of MN genotype = 2pq
• Frequency of NN genotype = q2

We can take a sample of the population and count the number of people with each genotype.For example, consider a sample of 2400 from Suburbia, USA, has:

• 730 individuals of type MM, or 30.42%
• 1225 of type MN, or 51.04%
• 445 of type NN, or 18.54%

Apply the Hardy-Weinberg equation (p2+ 2pq + q2= 1) to calculate the allele frequencies.There are several ways to accomplish this, such as:

• Frequency of M: p2+ 0.5 (2pq) = 0.3042 + (0.5 x 0.5104) = 0.559

1. Note: you have to use of the 2pq number because only half of the heterozygous alleles are M.The other half are N.

• Frequency of N: q = 1 - p = 1 - 0.559 = 0.441

With the allele frequencies in hand, we can apply the HW equation once more and calculate the expected genotype frequencies for a different population. For example, Metropolis, population 155,000:

• MM: p2= (0.559)2= 0.312, or 48,434 individuals
• MN: 2pq = 2 x 0.559 x 0.441 = 0.493, or 76,421 individuals
• NN = q2= (0.441)2= 0.194, or 30,145 individuals

However, what we know is that frequencies of the two alleles vary widely among human populations:

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