Medical Genetics

Medical genetics is the study of the interrelationship between human biological variation, including both genetic and environmental sources, and the phenotypic outcomes of health and disease. The field has rapidly moved to the forefront of biomedical research. Its overall goal is the detection and treatment of pathological genetic variation. In the past, medical genetics focused on genetic disorders such as chromosomal and single gene conditions, but increasingly medical geneticists are studying common diseases to which genes contribute significantly such as cancer and cardiovascular disease.

The prospect of preventing many diseases seems attainable today with the sequencing of the human genome and the application of genomic techniques to the characterization of disease-related genetic variation and specific mutations. The ultimate goal is to understand how genes contribute to an individual's susceptibility to disease and the individual's responses to the disease and to treatment. Identifying disease-associated genes, identifying novel molecular and genetic targets for chemotherapeutics, and even correcting defective genes through gene therapy hold tremendous promise in medicine. This promise, however, is feared to be advancing faster than society's ability to cope with the ethical considerations concerning what should be done with genetic information and specifically the genetic profiles for disease. The question lingers about how far society should go in modifying an individual's genetic makeup for any reason.

Eugenic concerns aside, medical genetics has revolutionized modern approaches to understanding and treating disease. Using a multidisciplinary approach to studying disease, the tools of medical genetics, genomics, and anthropology can produce a synthetic picture of a disease never attainable previously. [Page 1572]With the completion of the Human Genome Project, disease-associated genes are being discovered at an astounding rate while, at the same time, ancestral characteristics of populations are being defined at the genetic level. The latter are important in our understanding of the global and regional distribution of diseases among ethnic populations and the evolutionary and other contributors to disease variation among populations, a traditional research area in biological anthropology. Many of the disease-related genes and their inheritance characteristics have been made publicly available through online registries such as the National Center for Biotechnology Information (NCBI) and specifically the Online Mendelian Inheritance in Man (OMIM).

Sickle cell disease is a well-described example of studying a disease-causing gene at the population and individual levels and including the perspective of the environment. The mutation that results in the formation of hemoglobin S rather than the normal hemoglobin A causes a severe disease among individuals who are homozygous for the mutation, whereas the same mutation confers resistance to malaria in heterozygous individuals. Within malaria endemic regions, the mutation is maintained at relatively high rates through balancing selective pressures, that is, through the higher fitness (reproductive output) of heterozygous individuals in comparison with the two homozygous genotypes. Sickle cell disease is important in that it is probably the most completely researched example of natural selection in human populations. It is also a prime example of a genetic polymorphism, where the mutation is maintained in the population by selection. However, in African American and other populations no longer living in areas where malaria is endemic, such that there is no evolutionary advantage to this mutation, the frequency of the mutation is decreasing through relaxed selective pressure as well as admixture with other populations.

...