A form of dwarfism known as Ellis–van Creveld syndrome was first discovered in the late 1930s, 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.
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?

Verified step by step guidance

1. Recognize that Ellis–van Creveld syndrome is a genetic disorder inherited in an autosomal recessive manner, as affected individuals have unaffected parents, indicating carriers transmit the disorder without showing symptoms.
2. Understand that the high frequency of the disorder in the Pennsylvania Amish community suggests a founder effect, where a small group of ancestors (Samuel King and his wife) carried the mutation, which then increased in frequency due to limited genetic diversity and population isolation.
3. Note that the absence of the disorder in other Amish communities (Ohio or Indiana) supports the idea that these populations were founded by different ancestors who did not carry the mutation, leading to no cases of the disorder there.
4. Consider the role of genetic drift and inbreeding within the Pennsylvania Amish community, which can increase the frequency of rare alleles like the one causing Ellis–van Creveld syndrome, especially in a relatively closed population.
5. Summarize that the combination of a founder effect, genetic drift, and population isolation explains the high frequency of the disorder in the Pennsylvania Amish community and its absence in other Amish groups.

Key Concepts

Founder Effect

The founder effect occurs when a small group from a larger population establishes a new population, carrying only a fraction of the genetic variation. This can lead to a higher frequency of certain genetic traits or disorders if one or more founders carry the mutation. In the Pennsylvania Amish, the disorder likely originated from a common ancestor, increasing its prevalence.

Autosomal Recessive Inheritance

Autosomal recessive disorders require two copies of a mutated gene for the phenotype to appear. Affected individuals often have unaffected parents who are carriers. Ellis–van Creveld syndrome’s pattern, with affected children from unaffected parents, suggests recessive inheritance, explaining why the disorder appears in some families but not others.

Genetic Isolation and Population Bottlenecks

Genetic isolation occurs when a population is reproductively separated, limiting gene flow from outside groups. Population bottlenecks reduce genetic diversity due to a small number of ancestors. The Pennsylvania Amish community’s isolation and descent from a limited number of founders increased the frequency of the disorder, unlike other Amish groups with different founders.