The clinical specialty of medical genetics often deals with the detection and study of rare disorders encountered by chance when individuals or single families come to the attention of clinicians. Understanding the range of clinical findings and their etiology, however, usually requires the accumulation of a larger sample size which is difficult to obtain in most modern diverse populations. The Amish and related Anabaptist groups are exceptional in this regard. Because they generally live in isolated groups established by a limited number of founders, the resulting intermarriage can result in a high rate of consanguinity, which may lead to increased numbers of offspring with autosomal recessive heritable disorders. After nearly fifty years of genetic studies among Amish and other Anabaptist populations, researchers have identified more than 100 such conditions, many with substantial numbers of affected individuals. The study of these conditions provides unprecedented opportunities to enhance our understanding of human biology and the mechanisms of genetic disease.
The Amish have a number of social and demographic characteristics that create unique opportunities for the study of heritable disorders. As a result of their long tradition of intermarriage, or endogamy, and their principled separation from surrounding culture, the Amish tend to form relatively closed societies in which virtually everyone in their community is of German or Swiss Anabaptist ancestry. Because the number of founders was relatively small, present day descendents are nearly all related to each other through a limited number of common ancestors. In addition, until recently, they have tended to have limited geographic mobility; their distinctive dress and customs make it easy to identify members of the group; they frequently provide home-based care for individuals with special needs; their uniformly high standards of living help to minimize the impact of environmental factors in health-related disorders; they generally avail themselves of modern medical technology, which results in the extensive availability of medical records; and their clannish nature and extensive sharing of health issues both locally and through publications such as The Budget newspaper create networks of knowledge about individuals with health problems. (1) All these factors enhance the visibility of genetic disorders among the Amish, particularly those disorders that follow a specific pattern of inheritance known as "autosomal recessive."
BASIC PRINCIPLES GENETICS
Every human being has a distinctive genetic code contained in their DNA, or deoxyribonucleic acid. DNA is comprised of four molecules, called bases (adenine, guanine, cytosine and thymine--usually abbreviated to A, G, C and T). These are connected linearly into long strings, which are compacted and coiled in a highly complex but organized manner within the nucleus of human cells. DNA appears in its compacted form as chromosomes. Each cell contains 46 chromosomes, of which 23 are contributed by each parent. The human genetic code consists of triplets of these nucleic acids (i.e., specific sequences such as CGT, or AAA) which always select a specific amino acid that contributes to the construction of a protein. A gene is simply a string of such triplets, and their order determines the arrangement of amino acids that together make up a protein such as insulin, for example. Each of our trillions of cells contains about three billion DNA bases that make up about 25,000 genes. Together, these direct the synthesis of our body tissues and regulate the biochemical processes necessary to sustain life. With the exception of the genes on the sex chromosomes, we all inherit two copies of each gene, one from each of our parents.
Since most genes are normal, we often become aware of specific genes only when they change in some unusual manner. These changes are called mutations. …