In an era marked by rapid mobility of populations and increased social and economic interaction among diverse groups, the inevitable trend towards globalization has biological as well as economic and cultural consequences, states Senior Investigator Chester Alper, M.D.

This "population mixing," according to Alper, holds significant implications for the incidence of diseases determined by more than one gene, known as "polygenic" diseases.

Worldwide there is a rising incidence of polygenic diseases, which include type 1 diabetes, multiple sclerosis, autism, asthma, and celiac disease (gluten sensitivity). Incidence of type 1, or juvenile, diabetes is increasing 3 to 5 percent per year, while celiac disease may now affect five to ten out of every thousand Americans.

A recent article in the Journal of Autoimmunity -- based on studies of two groups of Caucasian families in Boston, Mass., by Zuheir Awdeh, Alper and colleagues - has for the first time provided concrete evidence for a causative link between population mixing and the rising incidence of type 1 diabetes. An earlier theoretical article by Awdeh and Alper in 2005, in Medical Hypotheses, detailed the new genetic principles behind the disease incidence-population mixing linkage and gave its mathematical basis.

In a nutshell, when a specific population has undergone selection against one or more of several disease susceptibility genes - the very genes required for a polygenic disease to occur - that population will, as a result of this selection, have a reduced incidence of the disease. However, when individuals from this population mix with populations that have selected against a different set of susceptibility genes, then their offspring will have a more complete set of these susceptibility genes than either parent. A higher incidence of polygenic diseases is the result.

This is counter-intuitive and the opposite of the concept of "hybrid vigor" which results in a reduction in incidence of recessive diseases caused by single genes. Diseases of this type include cystic fibrosis, sickle cell anemia, and Tay-Sachs Disease. Reduction in the incidence of these conditions is a positive aspect of genetic mixing. Alper's studies were based on previously isolated populations that include subpopulations of Caucasians. In England, for instance, there is a very high prevalence of type 1 diabetes in the Plymouth region; it is exactly there that subpopulations of Celts and Anglo-Saxons have historically undergone population mixing.

One line of evidence linking mixing of previously isolated populations to rising incidence of type 1 diabetes was self-reported ethnicity of grandparents. Parents of patients with type 1 diabetes exhibited about twice the ethnic heterogeneity (54%) of control parents (27%). Thus, the mixing was high in both groups of families but much higher in the families with type 1 diabetes patients.

Understanding genetic implications for disease incidence is an important issue of public health, says Alper. Learning about these mechanisms dovetails with the development of early intervention treatments that are being investigated for many diseases. These treatments include immunization, stem cell therapy, and pharmacologic agents. Moreover, increased knowledge about the genetic susceptibility of disease may contribute to medical science in ways that are unforeseen today.

It has been known for several years that the genetic makeup of type 1 diabetes patients as a group has changed over recent decades. However, many scientists asserted that changing environmental factors were the cause of the changing gene frequencies. Awdeh, Alper and colleagues are now countering that speculation by providing the conceptual framework for a purely genetic explanation for the observed genetic change.

Their revolutionary concepts and findings point to the need for new principles and experimental approaches to understanding polygenic diseases. Mendel and his genetic gospel still hold true. It is now a matter of adapting these principles to explain phenomena of the modern world. The work of Alper and his group directs us to focus on the new approaches for intervention and prevention being developed that are genetically based, rather than diverting energy and resources to speculative environmental or other external causes that are, in some cases contributory, but not determining.