Allelic Heterogeneity
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Allelic heterogeneity is the phenomenon in which different
mutations In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mi ...
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 traits of an organism. The term covers the organism's morphology or physical form and structure, its developmental processes, its biochemical and physiological proper ...
. 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. Charle ...
processes, as a result of
exogenous In a variety of contexts, exogeny or exogeneity () is the fact of an action or object originating externally. It contrasts with endogeneity or endogeny, the fact of being influenced within a system. Economics In an economic model, an exogeno ...
mutagen In genetics, a mutagen is a physical or chemical agent that permanently changes nucleic acid, genetic material, usually DNA, in an organism and thus increases the frequency of mutations above the natural background level. As many mutations can ca ...
s,
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 genetics, a single-nucleotide polymorphism (SNP ; plural SNPs ) is a germline substitution of a single nucleotide at a specific position in the genome. Although certain definitions require the substitution to be present in a sufficiently larg ...
in which a single nucleotide base is altered compared to a
consensus sequence In molecular biology and bioinformatics, the consensus sequence (or canonical sequence) is the calculated order of most frequent residues, either nucleotide or amino acid, found at each position in a sequence alignment. It serves as a simplified r ...
. 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 d ...
(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 A mitochondrion (; ) is an organelle found in the cells of most Eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is use ...
. 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 Pedigree may refer to: Breeding * Pedigree chart, a document to record ancestry, used by genealogists in study of human family lines, and in selective breeding of other animals ** Pedigree, a human genealogy (ancestry chart) ** Pedigree (animal ...
. 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 proper ...
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 acc ...
,
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 resu ...
. For example,
β-thalassemia Beta thalassemias (β thalassemias) are a group of genetic disorder, inherited hemoglobinopathy, blood disorders. They are forms of thalassemia caused by reduced or absent synthesis of the HBB, beta chains of hemoglobin that result in variable out ...
may be caused by several different mutations in the β-globin gene. Allelic heterogeneity should not be confused with
locus heterogeneity Locus heterogeneity occurs when mutations at multiple genomic loci are capable of producing the same phenotype (ie. a single trait, pattern of traits, or disorder), and each individual mutation is sufficient to cause the specific phenotype independe ...
in which a mutation at a different gene causes a similar phenotype. Nor should it be confused with
phenotypic heterogeneity Phenotypic heterogeneity describes different mutations in the same gene that can sometimes give rise to strikingly different phenotypes. E.g., certain loss-of-function mutations in the RET gene, which encodes a receptor tyrosine kinase, can caus ...
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.


See also

*
Locus heterogeneity Locus heterogeneity occurs when mutations at multiple genomic loci are capable of producing the same phenotype (ie. a single trait, pattern of traits, or disorder), and each individual mutation is sufficient to cause the specific phenotype independe ...


References

Mutation {{genetics-stub