Inbreeding

Inbreeding is defined as mating between related individuals. It is also called consanguinity, meaning "mixing of the blood." Although some plants successfully self-fertilize (the most extreme case of inbreeding), biological mechanisms are in place in many organisms, from fungi to humans, to encourage cross-fertilization. In human populations, customs and laws in many countries have been developed to prevent marriages between closely related individuals (e.g., siblings and first cousins). Despite these proscriptions, genetic counselors are frequently presented with the question "If I marry my cousin, what is the chance that we will have a baby who has a disease?" The answer is that when two partners are related their chance to have a baby with a disease or birth defect is higher than the background risk in the general population.

Increased Disease Risk

Many genetic diseases are recessive, meaning only people who inherit two disease alleles develop the disease. All of us carry several single alleles for genetic diseases. Since close relatives have more genes in common than unrelated individuals, there is an increased chance that parents who are closely related will have the same disease alleles and thus have a child who is homozygous for a recessive disease.

For instance, cousins share approximately one-eighth or 12.5 percent of their alleles. So, at any locus the chance that cousins share an allele inherited from a common parent is one-eighth. The chance that their offspring will inherit this allele from both parents, if each parent has one copy of the allele, is one-fourth. Thus, the risk the offspring will inherit two copies of the same allele is 1/8 × 1/4, or 1/32, about 3 percent. If this allele is deleterious , then the homozygous child will be affected by the disease. Overall, the risk associated with having a child affected with a recessive disease as a result of a first cousin mating is approximately 3 percent, in addition to the background risk of 3 to 4 percent that all couples face.

Inbreeding can be measured by the inbreeding coefficient (often denoted F). This is the probability that two genes at any locus in one individual are identical by descent (have been inherited from a common ancestor). F is larger the more closely related the parents are. For example, the coefficient of inbreeding for an offspring of two siblings is one-fourth (0.25), for an offspring of two half-siblings it is one-eighth (0.125), and for an offspring of two first cousins it is one-sixteenth (0.0625). (This is a different calculation than the calculation of shared alleles between cousins, above.)

In general, inbreeding in human populations is rare. The average inbreeding coefficient is 0.03 for the Dunker population in Pennsylvania and 0.04 for islanders on Tristan da Cunha. Inbreeding occurs in both those populations. Some isolated populations actively avoid inbreeding and have maintained low average inbreeding coefficients even though they are small. For example, polar Eskimos have an average inbreeding coefficient that is less than 0.003.

Beneficial changes can also come from inbreeding, and inbreeding is practiced routinely in animal breeding to enhance specific characteristics, such as milk production or low fat-to-muscle ratios in cows. However, there can often be deleterious effects of such selective breeding when genes controlling unselected traits are influenced too. Generations of inbreeding decrease genetic diversity, and this can be problematic for a species. Some endangered species, which have had their mating groups reduced to very small numbers, are losing important diversity as a result of inbreeding.

Genetic Studies of Inbred Populations

Inbred populations can offer a rich resource for genetic studies. They have the advantage of often being relatively homogeneous in both their genetics and environment. A method that has been used successfully to identify several recessive mutations in inbred groups is homozygosity mapping.

This approach looks for regions of alleles at genetic loci that are linked to one another and are homozygous. With inbreeding, there is an increased chance that, in an affected individual, the two alleles at the disease locus will have descended from a common ancestor. Therefore tightly linked markers (identifiable DNA segments) surrounding the disease locus will also tend to come from the same ancestral chromosome and thus be identical on both homologous chromosomes.

Together with colleagues, Erik Puffenberger, a research scientist and laboratory director at the Clinic for Special Children in Strasburg, Pennsylvania, capitalized on the inbreeding in a large Mennonite kindred to identify the location of a gene for Hirschprung disease on chromosome 13. In this family, parents of an affected child are, on average, related as closely as second or third cousins. The region was located because, true to theory, affected individuals shared alleles that were identical by descent at the region containing the disease gene.

see also Founder Effect; Inheritance Patterns; Pedigree; Population Genetics.

Eden R. Martin

and Marcy C. Speer

Bibliography

Cavalli-Sforza, Luigi L., and Walter F. Bodmer. The Genetics of Human Populations. Mineola, NY: Dover Publications, 1999.

Puffenberger Erik G., et al. "Identity-by-Descent and Association Mapping of a Recessive Gene for Hirschprung Disease on Human Chromosome 13q22." Human Molecular Genetics 3 (1994): 1217-1225.

Inbreeding

Inbreeding is the mating of organisms that are closely related or that share a common ancestry. It is used deliberately by people to try to retain desirable traits and eliminate undesirable ones in animals. However, inbreeding can result in harmful recessive genes that had been masked in parents but later appear in the offspring.

Inbreeding of animals has been conducted by people ever since they first began to keep animals for food, clothing, and transport. It probably was done initially when a particularly useful characteristic was displayed in an animal, and the animal was then encouraged to mate with another of its kind that had the same, desirable trait. Today, inbreeding is used in animal husbandry, which is the scientific control and management of animals. It is performed for the same original purpose of encouraging the development of certain desirable traits in offspring. A good example of inbreeding is done with dogs and cats who are bred primarily for their appearance. There are also some types of inbreeding that occur in nature. Self-fertilization is one example that occurs in bisexual flowering plants. This is probably the most "inbred" an organism can be since its offspring are the result of the fusion of the male and female sex cells of the same individual. This particular form of inbreeding is sometimes necessary since it allows an isolated individual plant to create a local population. One disadvantage of such an inbred population, however, is that its ability to adapt to environmental changes is limited since its members all share the same pool of genes.

This limitation of inbreeding applies to animals as well, and all farmers know that they can only mate animal siblings (brothers and sisters) for a few generations before they start to show signs of being less healthy and less fertile. The reason for this is because of the same lack of variability (genetic differences) that the isolated flower population suffered. Inbreeding can cause harmful genes that are recessive in both parents to become expressed in their offspring. A recessive gene is not expressed if there is a dominant one to offset it or mask it. However, it is still part of the individual's genetic makeup. The recessive gene will be expressed if the other parent also has a recessive gene for the same trait.

Continued inbreeding can result in an accumulation of recessive genes, which can cause what is called "inbreeding depression." This is not a state of mind but rather a physical state that results in low fertility, poor general health, and particularly negative characteristics like stunted growth or feebleness. One example of a species that is threatened by its lack of genetic diversity is the cheetah. Because today's existing cheetahs are all so closely related, most have weakened immune systems and are very susceptible to disease. To avoid this, agricultural breeders sometimes practice a form of inbreeding called "linebreeding." This is accomplished by mating a female animal with its grandfather or uncle (rather than with a sibling or parent). This reduces the probability of undesirable genes in the offspring.

The opposite of inbreeding is outbreeding, which is defined as mating individuals that are not related at all. While this can make it more difficult to regularly achieve a certain desirable quality or trait, it does produce more vigorous and healthy offspring. The most extreme example of outbreeding is called crossbreeding in which individuals of different but closely related species are mated. The mule is an example of the cross-breeding of a horse and a donkey, and although it is a very strong and useful animal, the mule is nonetheless sterile or cannot reproduce. This is the case with all crossbred animals.

[See alsoGenetic Disorders ]

inbreeding The interbreeding of closely related individuals (e.g. of siblings, or cousins, or a parent and its offspring). The converse is outbreeding. The inbreeding coefficient is the probability of homozygosity due to a zygote obtaining copies of the same gene from parents of common ancestry. Inbreeding increases homozygosity: unfavourable recessive genes are therefore more likely to be expressed in the offspring. In general, the genetic variability of an inbred population declines; this is usually disadvantageous for its long-term survival and success. Typically, vigour is reduced in inbred stock. Many organisms, including humans, have physical or social mechanisms that tend to discourage inbreeding and promote outbreeding.

inbreeding The interbreeding of closely related individuals (e.g. of siblings, or cousins, or a parent and its offspring). The converse is outbreeding. The inbreeding coefficient is the probability of homozygosity owing to a zygote obtaining copies of the same gene from parents of common ancestry. Inbreeding increases homozygosity: unfavourable recessive genes are therefore more likely to be expressed in the offspring. In general, the genetic variability of an inbred population declines; this is usually disadvantageous for its long-term survival and success. Typically, vigour is reduced in inbred stock. Many organisms, including humans, have physical or social mechanisms that tend to discourage inbreeding and promote outbreeding.

inbreeding Mating of two closely blood-related organisms. It is the opposite of outbreeding and over successive generations causes much less variation in genotype (genetic makeup) and phenotype (physical characteristics) than is normal in a wild population. A form of genetic engineering, it can be used to improve breeds in domestic plants and animals. In humans, it can have harmful results, such as the persistence of haemophilia in some European royal families.