Allelic heterogeneity is the phenomenon in which different mutations at the same

locus Locus (plural loci) is Latin for "place". It may refer to: Entertainment * Locus (comics), a Marvel Comics mutant villainess, a member of the Mutant Liberation Front * ''Locus'' (magazine), science fiction and fantasy magazine ** ''Locus Award' ...

lead to the same or very similar

phenotypes In genetics, the phenotype () is the set of observable characteristics or phenotypic trait, traits of an organism. The term covers the organism's morphology (biology), morphology or physical form and structure, its Developmental biology, dev ...

. These allelic variations can arise as a result of

natural selection Natural selection is the differential survival and reproduction of individuals due to differences in phenotype. It is a key mechanism of evolution, the change in the heritable traits characteristic of a population over generations. Cha ...

processes, as a result of exogenous mutagens,

genetic drift Genetic drift, also known as allelic drift or the Wright effect, is the change in the frequency of an existing gene variant (allele) in a population due to random chance. Genetic drift may cause gene variants to disappear completely and there ...

, or genetic migration. Many of these mutations take the form of single nucleotide polymorphisms in which a single nucleotide base is altered compared to a consensus sequence. They can also exist as

copy number variants Copy number variation (CNV) is a phenomenon in which sections of the genome are repeated and the number of repeats in the genome varies between individuals. Copy number variation is a type of structural variation: specifically, it is a type of G ...

(CNV) in which the copies of a gene or DNA sequence is different from the population. Mutated alleles expressing allelic heterogeneity can be classified as adaptive or disadaptive. These mutations can occur in the

germ line In biology and genetics, the germline is the population of a multicellular organism's cells that pass on their genetic material to the progeny (offspring). In other words, they are the cells that form the egg, sperm and the fertilised egg. They ...

cells,

somatic cells A somatic cell (from Ancient Greek σῶμα ''sôma'', meaning "body"), or vegetal cell, is any biological cell forming the body of a multicellular organism other than a gamete, germ cell, gametocyte or undifferentiated stem cell. Such cells compo ...

, or in the mitochondrial. Mutations in germ line cells can be inherited as well as mitochondrial allelic mutations. The mitochondrial allelic mutations are inherited maternally. Typically in the human genome a small amount of allele variants account for ~75% of the mutations found at a particular locus within a population. Other variants found are considered to be rare or exclusive to a single pedigree. The Online Mendelian Inheritance of Man has a record of over 1000 genes and their associated allelic variants. These genes display allelic heterogeneity at their loci and are responsible for distinct disease

phenotype In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology or physical form and structure, its developmental processes, its biochemical and physiological pr ...

s. Some of these diseases include

alkaptonuria Alkaptonuria is a rare inherited genetic disease which is caused by a mutation in the ''HGD'' gene for the enzyme homogentisate 1,2-dioxygenase (); if a person inherits an abnormal copy from both parents (it is a recessive condition), the body ac ...

albinism Albinism is the congenital absence of melanin in an animal or plant resulting in white hair, feathers, scales and skin and pink or blue eyes. Individuals with the condition are referred to as albino. Varied use and interpretation of the term ...

achondroplasia Achondroplasia is a genetic disorder with an autosomal dominant pattern of inheritance whose primary feature is dwarfism. In those with the condition, the arms and legs are short, while the torso is typically of normal length. Those affected ha ...

, and

phenylketonuria Phenylketonuria (PKU) is an inborn error of metabolism that results in decreased metabolism of the amino acid phenylalanine. Untreated PKU can lead to intellectual disability, seizures, behavioral problems, and mental disorders. It may also re ...

. For example,

β-thalassemia Beta thalassemias (β thalassemias) are a group of inherited blood disorders. They are forms of thalassemia caused by reduced or absent synthesis of the beta chains of hemoglobin that result in variable outcomes ranging from severe anemia to cli ...

may be caused by several different mutations in the β-globin gene. Allelic heterogeneity should not be confused with locus heterogeneity in which a mutation at a different gene causes a similar phenotype. Nor should it be confused with phenotypic heterogeneity in which a mutation within the same gene causes a different phenotype. Other major diseases displaying allelic heterogeneity are allelic mutations in the dystrophin gene which cause Duchenne dystrophy and mutations in the CFTR gene that are known to causes cystic fibrosis.

Alkaptonuria

The human gene for the HGD nucleotide sequence shows a number of AKU-causing allelic mutations. Approximately 40 different allelic variants have been documented. Most of these variants do not have an effect on the enzyme catalysis function. A few known alleles have an indirect effect on protein function by causing misfolding and disrupt the proper assembly of the enzyme complex. Alkaptunoria is considered to be a classic example of allelic heterogeneity showing a single variant in the human phenotype.

References

Mutation {{genetics-stub

Alkaptonuria

See also

References