Mary C. Maj

By Felicia Ikolo, Sabyasachi Maity, Robert Finn, Atoum Abdullah, Alireza Tajik, Jessie M. Cameron and Mary C. Maj

Animal models of genetic disorders that have risen due to selective breeding can be used as a valuable model to teach the basic concepts of population genetics. The Clumber Spaniel is a breed of dog created in the mid-1700s by the 4th Duc du Noailles. He selectively bred this dog for the elderly gentleman. This sleepy-looking breed survives today, though 1% suffer from severe exercise intolerance due to an autosomal-recessive founder mutation in the pyruvate dehydrogenase phosphatase 1 (PDP1) gene. PDP1 deficiency was long suspected to be a human metabolic disorder and described at the molecular level in 2005 by Robinson and coworkers. The Robinson group later identified a founder mutation within the PDP1 gene of the Clumber spaniel. This case clearly illustrates how a detrimental mutant allele in a small population, when selecting for phenotype, can persist in the progeny of that group. In this review, we discuss the origin of the “Founder Effect” theory and present an example of how a bottleneck that occurred during the selective breeding of the Clumber spaniel over 250 years ago led to the current genetic status of the breed. Today, genotyping can help reduce the incidence of PDP1 in the Clumber breed.

Part of the book: Population Genetics

By Mary C. Maj and Sharmila Upadhya

Multifactorial disorders include many common health conditions that affect our populations and are due to the interplay of genetic predispositions and the environment. Conditions such as diabetes, heart disease, asthma, and some cancers are often due to the combined interactions of a few to many genes, each of which has an impact on the overall phenotype of a person by either enhancing and/or masking each other’s effects. These genetic predispositions can also be significantly influenced by environmental factors. Environmental factors can range from those which are “fixed” to those that can be “modified.” Factors that are difficult to modify include geographical factors like air, water, and soil quality; socioeconomic factors such as access to resources; or occupational or household exposures to toxins. However, lifestyle factors are more amenable to modification including diet, exercise, and cessation of harmful habits. The combination of these diverse genetic and environmental factors influences the clinical severity of these complex disorders. To assess a patient’s risk for multifactorial disorders, healthcare providers have to consider a patient’s genetic information and have a detailed understanding of their background and lifestyle. Effective treatment recommendation further requires an understanding of the etiopathogenesis of the disorder. Appreciating the complexities of multifactorial inheritance helps clinicians explore personalized approaches to patient care to improve outcomes.

Part of the book: Advances and Trends in Population Genetics Studies