A null allele is a nonfunctional allele (a variant of a gene) caused by a genetic mutation. Such mutations can cause a complete lack of production of the associated gene product or a product that does not function properly; in either case, the allele may be considered nonfunctional. A null allele cannot be distinguished from deletion of the entire locus solely from phenotypic observation. A mutant allele that produces no RNA transcript is called an RNA null (shown by Northern blotting or by DNA sequencing of a deletion allele), and one that produces no protein is called a protein null (shown by Western blotting). A genetic null or amorphic allele has the same phenotype when homozygous as when heterozygous with a deficiency that disrupts the locus in question. A genetic null allele may be both a protein null and an RNA null, but may also express normal levels of a gene product that is nonfunctional due to mutation. Null alleles can have lethal effects depending on the importance of the mutated gene. For example, mice homozygous for a null allele for insulin die 48 to 72 hours after birth. Null alleles can also have beneficial effects, such as the elevated harvest index of semi-dwarf rice of the green revolution caused by null alleles in GA20ox-2.

Evidence

Polymerase chain reaction (PCR)

A microsatellite null allele is an allele at a microsatellite locus that does not amplify to detectable levels in a polymerase chain reaction test. Microsatellite regions are usually characterized by short, repeated sequences of nucleotides. Primers that are specific to a particular locus are used in PCR amplification to bind to these nucleotide sequence repeats and are used as genetic markers. The primers anneal to either end of the locus and are derived from source organisms in a genomic library. Divergence from the reference sequences (from genetic mutations) results in poor annealing of the primers so that the marker cannot be used, representative of a null allele.

Parentage analysis

Strong evidence of null alleles was first seen in analysis of bears in 1995. In this analysis, a known parent was determined to be homozygous at a certain locus, but produced offspring that expressed a different "homozygous" genotype. This result led to the inference that the parent and offspring were both heterozygous for the locus being studied.

Examples

Null alleles or genes have been studied in different organisms from the red pines of Minnesota to Drosophila melanogaster and mice. Null alleles are difficult to identify because a heterozygous individual for one null allele and one active allele is phenotypically indistinguishable from a homozygous individual with both active alleles. In other words, a null allele can only be identified from the phenotypic standpoint if the individual is homozygous for the null allele. Researchers have been able to work around this problem by using detailed Electrophoresis, gel assays, and chromosomal manipulation.