Medical genetics

Overview
Medical Genetics is the application of genetics to medicine. Medical genetics is a broad and varied field. It encompasses many different individual fields, including clinical genetics, biochemical genetics, cytogenetics, molecular genetics, the genetics of common diseases (such as neural tube defects), and genetic counseling.

Each of the individual fields within medical genetics is a hybrid. Clinical genetics is a hybrid of clinical medicine with genetics. Biochemical genetics is a hybrid of biochemistry, mainly of amino acids and proteins, with genetics. Molecular genetics is a hybrid of the biochemistry of DNA and RNA with genetics. Cytogenetics is a hybrid of cytology and genetics; it involves the study of chromosomes under the microscope. Genetic counseling is a hybrid of genetics and nondirectional counseling.

Nomenclature
Human genetics differs from medical genetics in that human genetics may or may not apply to medicine, but medical genetics always applies to medicine. The study of Huntington disease (a progressive neurologic disease) is properly part of both human genetics and medical genetics, whereas the study of eye color (except in situations such as albinism) is part of human genetics but not medical genetics.


 * Genetic medicine is a newer term for medical genetics.

A Short History
Although genetics has its roots back in the 19th century with the work of the Bohemian monk Gregor Mendel and other pioneering scientists, human genetics emerged later. It started to develop, albeit slowly, during the first half of the 20th century. Mendelian (single-gene) inheritance was studied in a number of important disorders such as albinism, brachydactyly (short fingers and toes), and hemophilia. Mathematical appoaches were also devised and applied to human genetics. Population genetics was created.

Medical genetics was a late developer, emerging largely after the close of World War II (1945) when the eugenics movement had fallen into disrepute. The Nazi misuse of eugenics sounded its death knell. Shorn of eugenics, a scientific approach could be used and was applied to human and medical genetics. Medical genetics saw an increasingly rapid rise in the second half of the 20th century and continues in the 21st century.

The allelic architecture of disease
Sometimes the link between a disease and an unusual gene variant is more subtle. The genetic architecture of common diseases is an important factor in determining the extent to which patterns of genetic variation influence group differences in health outcomes. According to the common disease/common variant hypothesis, common variants present in the ancestral population before the dispersal of modern humans from Africa play an important role in human diseases. Genetic variants associated with Alzheimer disease, deep venous thrombosis, Crohn disease, and type 2 diabetes appear to adhere to this model. However, the generality of the model has not yet been established and, in some cases, is in doubt. Some diseases, such as many common cancers, appear not to be well described by the common disease/common variant model.

Another possibility is that common diseases arise in part through the action of combinations of variants that are individually rare. Most of the disease-associated alleles discovered to date have been rare, and rare variants are more likely than common variants to be differentially distributed among groups distinguished by ancestry. However, groups could harbor different, though perhaps overlapping, sets of rare variants, which would reduce contrasts between groups in the incidence of the disease.

The number of variants contributing to a disease and the interactions among those variants also could influence the distribution of diseases among groups. The difficulty that has been encountered in finding contributory alleles for complex diseases and in replicating positive associations suggests that many complex diseases involve numerous variants rather than a moderate number of alleles, and the influence of any given variant may depend in critical ways on the genetic and environmental background. If many alleles are required to increase susceptibility to a disease, the odds are low that the necessary combination of alleles would become concentrated in a particular group purely through drift.

Population substructure in genetics research
One area in which population categories can be important considerations in genetics research is in controlling for confounding between population substructure, environmental exposures, and health outcomes. Association studies can produce spurious results if cases and controls have differing allele frequencies for genes that are not related to the disease being studied, although the magnitude of this problem in genetic association studies is subject to debate. Various methods have been developed to detect and account for population substructure, but these methods can be difficult to apply in practice.

Population substructure also can be used to advantage in genetic association studies. For example, populations that represent recent mixtures of geographically separated ancestral groups can exhibit longer-range linkage disequilibrium between susceptibility alleles and genetic markers than is the case for other populations. Genetic studies can use this admixture linkage disequilibrium to search for disease alleles with fewer markers than would be needed otherwise. Association studies also can take advantage of the contrasting experiences of racial or ethnic groups, including migrant groups, to search for interactions between particular alleles and environmental factors that might influence health.

Organizations
The more empirical approach to human and medical genetics was formalized by the founding in 1948 of the American Society of Human Genetics. The Society first began annual meetings that year (1948) and its international counterpart, the International Congress of Human Genetics, has met every 5 years since its inception in 1956. The Society publishes the American Journal of Human Genetics on a monthly basis. Medical genetics is now recognized as a distinct medical specialty in the U.S. with its own approved board (the American Board of Medical Genetics) and clinical specialty college (the American College of Medical Genetics). The College holds an annual scientific meeting, publishes a monthly journal, Genetics in Medicine, and issues position papers and clinical practice guidelines on a variety of topics relevant to human genetics.

Resources
For patients, their families or other individuals seeking good information and support groups, the National Institutes of Health offers the office of rare diseases, genetics home reference, medlineplus and health information. The National Human Genome Research Institute hosts an information center, a section for patients and the public and additional educational resources. Support groups can be found at NORD, Genetic Alliance and Orphanet. The genetic education center at the KUMC has many more useful links.

See inborn errors of metabolism for more resources related to that field.