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 \(1940 .\) Affected individuals 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 community, about 5 per 1000 births are affected, and in the population of \(8000,\) the observed frequency is 2 per \(1000 .\) All affected individuals have unaffected parents, and all affected cases can trace their ancestry 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: Ellis-van Creveld syndrome is inherited in an autosomal recessive manner. The high frequency of the disorder in the Pennsylvania Amish community can be attributed to genetic drift and founder effect as the community is relatively isolated and has a small population, increasing the likelihood of mating between individuals carrying the same rare mutant allele.

Step-by-step solution

(a) Determine the mode of inheritance of Ellis-van Creveld syndrome

The affected individuals have unaffected parents since all affected cases can trace their ancestry to Samuel King and his wife who were both not affected. This information suggests that the syndrome is inherited in an autosomal recessive manner as the parents are carriers, but do not display the disorder themselves. So let's assume that the disorder follows the autosomal recessive pattern of inheritance.

Calculate the frequency of the mutant allele (q) and the frequency of heterozygotes (2pq)

Let p represent the frequency of the dominant allele (unaffected) and q represent the frequency of the recessive allele (mutant). From Hardy-Weinberg law, we have p^2 + 2pq + q^2 = 1 where p^2 represents the frequency of homozygous dominant individuals, 2pq represents the frequency of heterozygotes, and q^2 represents the frequency of homozygous recessive individuals. Given the frequency of affected individuals in the population: q^2 = 2/1000 = 0.002 Now, we can find the frequency of the mutant allele (q) by taking the square root of q^2: q = sqrt(0.002) ≈ 0.0447 Since p + q = 1, we can find the frequency of the dominant allele (p) by subtracting q from 1: p = 1 - q ≈ 1 - 0.0447 ≈ 0.9553 Now, we can find the frequency of heterozygotes (2pq) using the values of p and q: 2pq = 2 * 0.9553 * 0.0447 ≈ 0.0854 Thus, the frequency of the mutant allele (q) in the population is 0.0447, and the frequency of heterozygotes (2pq) is 0.0854.

(b) Explain the high frequency of the disorder in the Pennsylvania Amish community

The high frequency of the Ellis-van Creveld syndrome in the Pennsylvania Amish community can be attributed to genetic drift and founder effect. The Amish population in eastern Pennsylvania is a relatively isolated and small group, which increases the likelihood of mating between individuals who carry the same rare mutant allele. The high frequency of this disorder in this particular community but not in other Amish communities in Ohio or Indiana could be due to the fact that the common ancestors of this community, Samuel King and his wife, were carriers of the mutant allele for this syndrome. The concentration of this rare allele might've been passed through generations in this Pennsylvania community but was not present in other Amish communities, as they don't share ancestry with the carriers of this allele.