Question

A form of dwarfism known as Ellis-van Creveld syndrome was first discovered in the late 1930 s, when Richard Ellis and simon van Creveld shared a train compartment on the way to a pediatrics meeting. In the course of conversation, they discovered that they each had a patient with this syndrome. They published a description of the syndrome in \(1940 .\) Individuals with this syndrome have a short-limbed form of dwarfism and often have defects of the lips and teeth, and polydactyly (extra fingers). The largest pedigree for the condition was reported in an Old Order Amish population in eastern Pennsylvania by Victor McKusick and his colleagues \((1964) .\) In that population of \(8000,\) the observed frequency is 2 per \(1000 .\) In all cases, parents of children with the syndrome were unaffected, and all cases can be traced to Samuel King and his wife, who arrived in the area in \(1774 .\) It is known that neither King nor his wife was affected with the disorder. There are no cases of the disorder in other Amish communities, such as those in Ohio or Indiana. (a) From the information provided, derive the most likely mode of inheritance of this disorder. Using the Hardy-Weinberg law, calculate the frequency of the mutant allele in the population and the frequency of heterozygotes, assuming Hardy-Weinberg conditions. (b) What is the most likely explanation for the high frequency of the disorder in the Pennsylvania Amish community and its absence in other Amish communities?

Short answer

Answer: The high frequency of Ellis-van Creveld syndrome in the Pennsylvania Amish community is most likely due to the founder effect. The condition is traced back to one couple, who were carriers of the mutant allele, which got passed on to their descendants. The Amish community is well-known for being closed and having minimal gene flow with other populations, which can lead to an increase in the frequency of certain recessive traits. The absence of the disorder in other Amish communities can also be explained by the founder effect. Since the mutation originated from one couple in the Pennsylvania community, other Amish communities that were established by founders without the mutation would not have the disorder present in their populations.

Step-by-step solution

Determine the mode of inheritance

Since the parents of affected individuals are unaffected, this suggests a recessive mode of inheritance. Additionally, the disorder can be traced back to one couple, which supports the idea of a recessive trait being passed down from carriers.

Calculate the frequency of affected individuals

Given that the observed frequency is 2 per 1000 in the population of 8000, we can calculate the frequency of affected individuals (q^2) as follows: q^2 = \frac{2}{1000} = 0.002

Calculate the frequency of the mutant allele (q)

To calculate the frequency of the mutant allele (q), we need to take the square root of q^2 as follows: q = \sqrt{0.002} = 0.0447

Calculate the frequency of the normal allele (p)

Now, we need to find the frequency of the normal allele (p). Since p + q = 1, we can find p as follows: p = 1 - q = 1 - 0.0447 = 0.9553

Calculate the frequency of heterozygotes

Using the Hardy-Weinberg law, we can now calculate the frequency of heterozygotes, which is 2pq: 2pq = 2 * 0.9553 * 0.0447 = 0.0856 Therefore, the frequency of heterozygotes in the population is 0.0856.

Explain the high frequency in the Pennsylvania Amish community

The high frequency of Ellis-van Creveld syndrome in the Pennsylvania Amish community is most likely due to the founder effect. The condition is traced back to one couple, who were carriers of the mutant allele, which got passed on to their descendants. The Amish community is well-known for being closed and having minimal gene flow with other populations, which can lead to an increase in the frequency of certain recessive traits.

Explain the absence of the disorder in other Amish communities

The absence of the disorder in other Amish communities can also be explained by the founder effect. Since the mutation originated from one couple in the Pennsylvania community, other Amish communities that were established by founders without the mutation would not have the disorder present in their populations.