Question

Familial Mediterranean Fever (FMF) is an autosomal recessive genetic condition due to mutations in the MEFV gene that encodes pyrin, a protein that functions in the immune inflammatory response.

The following numbers are from a representative sample of individuals from Greece with their respective genotypes. (note- capital letters indicate the wildtype allele and lower-case letters represent mutant allele)

216   MEFV/MEVF                  82 MEVF/mevf                       4 mevf/mevf

In France, the incidence of Familial Mediterranean Fever is 0.80% or 0.008. Use this to answer the following questions:

1. What is the frequency of the mutant mevf allele in France?

2. What is the carrier frequency (frequency of heterozygous genotype) in France?

3. In 2-3 sentences, describe why or how the mevf mutant allele persists in certain populations over time.

Answer 1

Familial Mediterranean Fever (FMF) is an autosomal recessive genetic condition due to mutations in the MEFV gene.

Presence of homozygous recessive gene leads to FMF.

mevf/mevf = Affected

MEVF/mevf = Carrier

MEVF/MEVF = normal

Given the incidence of FMF is 0.008 which means,

Frequency of Genotype mevf/mevf, q^2 = 0.008

q = √0.008

q = 0.089

According to Hardy Weinberg Equilibrium,

p + q = 1

p = 1 - q

p = 1 - 0.089 = 0.911

q is the frequency of mutant allele, mevf = 0.089

p is the frequency of wild type allele, MEVF = 0.911

The carrier frequency, i.e. the frequency of Heterozygous condition = 2pq

= 2 × (0.911) × (0.089)

= 0.162

Now, we can verify that

p^2 + 2pq + q^2 = 1

(0.911)^2 + 2 × (0.911) × (0.089) + (0.089)^2

= 0.83 + 0.162 + 0.008

= 1

1) The frequency of mutant allele in France is 0.089

2) Frequency of the carrier (Heterozygous Genotype) of France is 0.162

3) mevf Mutant allele persists over time in certain population because they are present in heterozygous forms as carriers. These carriers transfer/pass on this recessive allele to the next generation allowing them to persist in the gene pool. Generally Natural selection reduce the frequency of disease-associated alleles, but other evolutionary processes such as mutation and gene flow, may introduce/incrrease in the frequency of these deleterious alleles.

Thus this mutant gene persists over time in certain population.