Consanguinity and genetic disease

SIGNIFICANCE: The late onset of sexual maturity and the random mating habits of most humans make studying rare mutations in human populations especially difficult. Small, isolated communities in which mates are chosen only from within the population lead to consanguineous populations that can serve as natural laboratories for the study of human genetics, especially in the area of human disease.

The Importance of Isolates

When studying the genetics of the fruit fly or any other organism commonly used in the laboratory, a researcher can choose the genotypes of the flies that will be mated and can observe the next few generations in a reasonable amount of time. Experimenters can also choose to mate offspring flies with their siblings or with their parents. As one might expect, this is not possible when studying the inheritance of human characteristics. Thus, progress in human genetics most often relies on the observation of the phenotypes of progeny that already exist and matings that have already occurred. Many genetic diseases only appear when a person is for two recessive alleles; thus a person must inherit the same recessive allele from both parents. Since most recessive alleles are rare in the general population, the chance that both parents carry the same recessive allele is small. This makes the study of these diseases very difficult. The chance that both parents carry the same recessive allele is increased whenever mating occurs between individuals who share some of the same genetic background. These consanguineous matings produce measurably higher numbers of offspring with genetic diseases, especially when the degree of consanguinity is at the level of second cousin or closer.

In small religious communities in which marriage outside the religion is forbidden, and in small, geographically isolated populations in which migration into the population from the outside is at or near zero, marriages often occur between two people who share some common ancestry; therefore, the level of consanguinity can be quite high. According to a 2024 study published in the journal Cureus, about 20 percent of the world’s population lives in regions where such marriage arrangements are preferred. The rate ranged from a low of 0.5 percent in Western and European societies, to 20 to 50 percent in some Arab societies in the Middle East.

These communities thus serve as natural laboratories in which to study genetic diseases. Geographically isolated mountain and island communities are found in many areas of the world, including the Caucasus Mountains of Eurasia, the Appalachian Mountains of North America, and many areas in the South Pacific. Culturally isolated communities are also of worldwide distribution. Among the Druse, a small Islamic sect, first-cousin marriages approach 50 percent of all marriages. The Amish, Hutterites, and Dunkers in the United States are each descended from small groups of original settlers who immigrated in the eighteenth and nineteenth centuries and rarely mated with people from outside their religions.

The Amish

There are many reasons the Amish serve as a good example of an isolate. The original immigration of Amish to America consisted of approximately two hundred settlers. In subsequent generations, the available mates came from the descendants of the original settlers. With mate choice this limited, it is inevitable that some of the marriages will be consanguineous. Consanguinity increases as further marriages take place between the offspring of consanguineous marriages. Current estimates are that the average degree of consanguinity of Amish marriages in Lancaster County, Pennsylvania, is at the level of marriages between second cousins.

Other factors that make the Amish good subjects for genetic research are their high fertility and their high level of marital fidelity. Thus, if both parents happen to be for a particular genetic disease, the chance that at least one of the offspring will show the disease is high. In families of two children, there is a 44 percent chance that at least one child will show the trait. This increases to 70 percent of the families with four children and to more than 91 percent of the families with eight children, a common number among the Amish. Because of the high marital fidelity, researchers do not have to worry about illegitimacy when making these estimates.

Many genetic diseases that are nearly nonexistent in the general population are found among the Amish. The allele for a type of dwarfism known as the Ellis-van Creveld syndrome is found in less than 0.1 percent of the general population; among the Lancaster Amish, however, the allele exists in approximately 7 percent of the population. Other genetic diseases at higher levels among the Amish include cystic fibrosis, limb-girdle muscular dystrophy, pyruvate kinase-deficient hemolytic anemia, and several inherited psychological disorders. Having more families and individuals with these diseases to study helps geneticists and physicians discover ways to treat the problems and even prevent them from occurring.

Key Terms

• allelesgenetic variants of a particular gene
• consanguineousliterally, “of the same blood,” or sharing a common genetic ancestry; members of the same family are consanguineous to varying degrees
• isolatea community in which mates are chosen from within the local population rather than from outside populations

Bibliography

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