Null allele
Encyclopedia
A null allele is a mutant copy of a gene
that completely lacks that gene's normal function. This can be the result of the complete absence of the gene
product (protein, RNA) at the molecular level, or the expression of a non-functional gene product. At the phenotypic
level, a null allele is indistinguishable from a deletion of the entire locus
.
A mutant allele that produces no protein is called a protein null (shown by western analysis
), and one that produces no RNA is called an RNA null (shown by Northern analysis
or by DNA sequencing of a deletion allele). A genetic null or amorph
ic allele has the same phenotype when homozygous as when heterozygous with a deficiency that disrupts the locus in question. A genetic null allele can be a protein and RNA null, but can also express normal levels of a gene product that is non-functional due to mutation.
Another definition of null allele concerning molecular markers, refers to such a marker in the case it can no longer be detected because of a mutation. For example, microsatellites (i.e. a repetitive sequence of DNA, in which the repeat is rather short) are used as molecular markers amplifying them through PCR
. To do so, a primer
or oligonucleotide
aligns with either of ends of the locus. If a mutation occurs in the annealing site, then the marker can no longer be used and the allele is turned into a null allele.
One example of a null allele is the 'O' blood type allele in the human A, B and O blood type system. The alleles for the A-antigen
and B-antigen are co-dominant
, thus they are both phenotypically
expressed if both are present. The allele for O blood type, however, is a mutated version of the allele for the A-antigen, with a single base pair
change due to genetic mutation. The protein
coded for by the O allele is enzymatically inactive and therefore the O allele is expressed phenotypically in homozygous
OO individuals as the lack of any blood antigen. Thus we may consider the allele for the O blood type as a null allele.
Allele
An allele is one of two or more forms of a gene or a genetic locus . "Allel" is an abbreviation of allelomorph. Sometimes, different alleles can result in different observable phenotypic traits, such as different pigmentation...
that completely lacks that gene's normal function. This can be the result of the complete absence of the gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
product (protein, RNA) at the molecular level, or the expression of a non-functional gene product. At the phenotypic
Phenotype
A phenotype is an organism's observable characteristics or traits: such as its morphology, development, biochemical or physiological properties, behavior, and products of behavior...
level, a null allele is indistinguishable from a deletion of the entire locus
Locus (genetics)
In the fields of genetics and genetic computation, a locus is the specific location of a gene or DNA sequence on a chromosome. A variant of the DNA sequence at a given locus is called an allele. The ordered list of loci known for a particular genome is called a genetic map...
.
A mutant allele that produces no protein is called a protein null (shown by western analysis
Western blot
The western blot is a widely used analytical technique used to detect specific proteins in the given sample of tissue homogenate or extract. It uses gel electrophoresis to separate native proteins by 3-D structure or denatured proteins by the length of the polypeptide...
), and one that produces no RNA is called an RNA null (shown by Northern analysis
Northern blot
The northern blot is a technique used in molecular biology research to study gene expression by detection of RNA in a sample. With northern blotting it is possible to observe cellular control over structure and function by determining the particular gene expression levels during differentiation,...
or by DNA sequencing of a deletion allele). A genetic null or amorph
Muller's morphs
1946 Nobel Prize winner Hermann J. Muller coined the terms amorph, hypomorph, hypermorph, antimorph and neomorph to classify mutations based on their behaviour in various genetic situations. These classifications are still widely used in Drosophila genetics to describe mutations...
ic allele has the same phenotype when homozygous as when heterozygous with a deficiency that disrupts the locus in question. A genetic null allele can be a protein and RNA null, but can also express normal levels of a gene product that is non-functional due to mutation.
Another definition of null allele concerning molecular markers, refers to such a marker in the case it can no longer be detected because of a mutation. For example, microsatellites (i.e. a repetitive sequence of DNA, in which the repeat is rather short) are used as molecular markers amplifying them through PCR
Polymerase chain reaction
The polymerase chain reaction is a scientific technique in molecular biology to amplify a single or a few copies of a piece of DNA across several orders of magnitude, generating thousands to millions of copies of a particular DNA sequence....
. To do so, a primer
Primer (molecular biology)
A primer is a strand of nucleic acid that serves as a starting point for DNA synthesis. They are required for DNA replication because the enzymes that catalyze this process, DNA polymerases, can only add new nucleotides to an existing strand of DNA...
or oligonucleotide
Oligonucleotide
An oligonucleotide is a short nucleic acid polymer, typically with fifty or fewer bases. Although they can be formed by bond cleavage of longer segments, they are now more commonly synthesized, in a sequence-specific manner, from individual nucleoside phosphoramidites...
aligns with either of ends of the locus. If a mutation occurs in the annealing site, then the marker can no longer be used and the allele is turned into a null allele.
One example of a null allele is the 'O' blood type allele in the human A, B and O blood type system. The alleles for the A-antigen
Antigen
An antigen is a foreign molecule that, when introduced into the body, triggers the production of an antibody by the immune system. The immune system will then kill or neutralize the antigen that is recognized as a foreign and potentially harmful invader. These invaders can be molecules such as...
and B-antigen are co-dominant
Dominance relationship
Dominance in genetics is a relationship between two variant forms of a single gene, in which one allele masks the effect of the other in influencing some trait. In the simplest case, if a gene exists in two allelic forms , three combinations of alleles are possible: AA, AB, and BB...
, thus they are both phenotypically
Phenotype
A phenotype is an organism's observable characteristics or traits: such as its morphology, development, biochemical or physiological properties, behavior, and products of behavior...
expressed if both are present. The allele for O blood type, however, is a mutated version of the allele for the A-antigen, with a single base pair
Base pair
In molecular biology and genetics, the linking between two nitrogenous bases on opposite complementary DNA or certain types of RNA strands that are connected via hydrogen bonds is called a base pair...
change due to genetic mutation. The protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
coded for by the O allele is enzymatically inactive and therefore the O allele is expressed phenotypically in homozygous
Zygosity
Zygosity refers to the similarity of alleles for a trait in an organism. If both alleles are the same, the organism is homozygous for the trait. If both alleles are different, the organism is heterozygous for that trait...
OO individuals as the lack of any blood antigen. Thus we may consider the allele for the O blood type as a null allele.
See also
- amorphMuller's morphs1946 Nobel Prize winner Hermann J. Muller coined the terms amorph, hypomorph, hypermorph, antimorph and neomorph to classify mutations based on their behaviour in various genetic situations. These classifications are still widely used in Drosophila genetics to describe mutations...
- Genetic deletionGenetic deletionIn genetics, a deletion is a mutation in which a part of a chromosome or a sequence of DNA is missing. Deletion is the loss of genetic material. Any number of nucleotides can be deleted, from a single base to an entire piece of chromosome...
- RecLOHRecLOHRecLOH is a term in genetics that is an abbreviation for "Recombinational Loss of Heterozygosity".This is a type of mutation which occurs with DNA by recombination. From a pair of equivalent , but slightly different genes, a pair of identical genes results...
- Unique-event polymorphism