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Inbreeding

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.

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inbreeding

inbreeding, mating of closely related organisms. Inbreeding is chiefly used as a means of insuring the preservation of specific desired traits among the offspring of purebred animals (see breeding). Continued inbreeding through many generations reduces the chances for diversity of characteristics in the offspring and tends to reduce vigor and fertility. Only in laboratory conditions can the unwanted characteristics that frequently result from inbreeding be selected out of the strain and selection for purely advantageous traits be carried out. The necessarily uncontrolled cases of inbreeding among humans (as in closed societies or within royal families) have generally proved deleterious, and inbreeding is therefore discouraged in most societies (see consanguinity; incest).

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inbreeding

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.

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inbreeding

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.

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inbreeding

inbreeding Mating between closely related individuals, the extreme condition being self-fertilization, which occurs in many plants and some primitive animals. A population of inbreeding individuals generally shows less variation than an outbreeding population. Continued inbreeding among a normally outbreeding population leads to inbreeding depression (the opposite of hybrid vigour) and an increased incidence of harmful characteristics. For example, in humans, certain mental and other defects tend to occur more often in families with a history of cousin marriages.

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inbreeding

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.

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inbreeding

inbreeding (in-breed-ing) n. the production of offspring by parents who are closely related. Compare outbreeding.

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