George J. Feldman, PhD, DMD

My lab is focused on identifying and understanding the causes of major crippling orthopaedic disorders that are genetically transmitted in families. Currently we are trying to find causative mutations for the complex disorder Developmental Dysplasia of the Hip (DDH). DDH is caused by the incomplete formation of the hip socket or acetabulum in individuals. This allows the head of the thigh bone or femur to easily dislocate and cause extra wear in the acetabulum often leading to osteoarthritis. While DDH is a complex disease to which environmental influences contribute, there is strong evidence of intergenerational transmission in human families. Although the overall prevalence of DDH in the US population is 1% in newborns undiagnosed DDH is thought to contribute to over 40% of all cases of osteoarthritis in young adults. Current screening tests in infants thus miss a large portion of affected individuals. Our goal is to develop genetic tests to detect the mutations that make an individual susceptible to this disorder. Early intervention with the Pavlik harness and other devices could then be used in these individuals to encourage acetabular development.

We are attempting to find causative mutations using 2 different approaches:

1. Traditional linkage analysis. We have recruited a number of DDH affected families and have retrieved DNA from their peripheral blood and cheek swabs. We are using the Affymetrix platform to identify those single nucleotide polymorphisms that co-segregate with affected individuals but are absent from unaffected relatives.
2. Some DDH affected individuals are more affected than others. We have identified a severely affected family some of whose members have bilateral DDH. We hypothesize that the severity of their disease might be explained by a variation in the copy number of larger segments of their DNA. To test this hypothesis we are planning to hybridize their DNAs to specifically designed Affymetrix chips to search for copy number variations that are shared by affected individuals but not by the unaffected relatives or other controls.