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Multiple Alleles

Multiple Alleles

Alleles are alternative forms of a gene, and they are responsible for differences in phenotypic expression of a given trait (e.g., brown eyes versus green eyes). A gene for which at least two alleles exist is said to be polymorphic. Instances in which a particular gene may exist in three or more allelic forms are known as multiple allele conditions. It is important to note that while multiple alleles occur and are maintained within a population, any individual possesses only two such alleles (at equivalent loci on homologous chromosomes).

Examples of Multiple Alleles

Two human examples of multiple-allele genes are the gene of the ABO blood group system, and the human-leukocyte-associated antigen (HLA) genes.

The ABO system in humans is controlled by three alleles, usually referred to as IA, IB, and IO (the "I" stands for isohaemagglutinin). IA and IB are codominant and produce type A and type B antigens, respectively, which migrate to the surface of red blood cells, while IO is the recessive allele and produces no antigen. The blood groups arising from the different possible genotypes are summarized in the following table.

Genotype Blood Group
IA IA A
IA IO A
IB IB B
IB IO B
IA IB AB
IO IO O

HLA genes code for protein antigens that are expressed in most human cell types and play an important role in immune responses. These antigens are also the main class of molecule responsible for organ rejections following transplantationsthus their alternative name: major histocompatibility complex (MHC) genes.

The most striking feature of HLA genes is their high degree of polymorphism there may be as many as one hundred different alleles at a single locus. If one also considers that an individual possesses five or more HLA loci, it becomes clear why donor-recipient matches for organ transplantations are so rare (the fewer HLA antigens the donor and recipient have in common, the greater the chance of rejection).

Polymorphism in Noncoding DNA

It must be realized that although the above two are valid examples, most genes are not multiply allelic but exist only in one or two forms within a population. Most of the DNA sequence variation between individuals arises not because of differences in the genes, but because of differences in the noncoding DNA found between genes.

An example of a noncoding DNA sequence that is extremely abundant in humans is the so-called microsatellite DNA. Microsatellite sequences consist of a small number of nucleotides repeated up to twenty or thirty times. For instance, the microsatellite composed of the dinucleotide AC is very common, appearing about one hundred thousand times throughout the human genome.

The interesting feature about microsatellites is that they are very highly polymorphic for the number of repeat lengths. For example, one particular individual might possess the microsatellite sequence ACACACACAC at a specific locus on one chromosome, and the sequence ACACACACACACACACAC at the same locus on the other homologous chromosome.

Making Use of Polymorphic DNA

Multiple alleles and noncoding polymorphic DNA are of considerable importance in gene mappingidentifying the relative positions of genetic loci on chromosomes. Gene maps are constructed by using the frequency of crossing-over to estimate the distance between a pair of loci. To obtain a good estimate, one must analyze a large number of offspring from a single cross. In laboratory organisms such as the fruit fly Drosophila, programmed crosses can be carried out so it is possible to use gene loci to construct a reliable genetic map. In humans, this is not the case. For this reason, the more highly variable noncoding regions are of considerable importance in human genetic mapping.

see also Blood Type; Immune System Genetics; Mapping; Polymorphisms; Transplantation.

Andrea Bernasconi

Bibliography

Alberts, Bruce, et al. Molecular Biology of the Cell, 4th ed. New York: Garland, 2002.

Strachan, Tom, and Andrew P. Read. Human Molecular Genetics. New York: Bios Scientific Publishers, 1996.

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multiple alleles

multiple alleles Three or more alternative forms of a gene (alleles) that can occupy the same locus. However, only two of the alleles can be present in a single organism. For example, the ABO system of blood groups is controlled by three alleles, only two of which are present in an individual.

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