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Lethal alleles (also referred to as lethal genes or lethals) are alleles that cause the death of the organism that carry them. They are usually a result of mutations in genes that are essential to growth or development. Lethal alleles may be recessive, dominant, or conditional depending on the gene or genes involved. Lethal alleles can cause death of an organism prenatally or any time after birth, though they commonly manifest early in development.

History
Lethal alleles were first discovered by Lucien Cuénot in 1905 while studying the inheritance of coat colour in mice. The agouti gene in mice is largely responsible for determining coat colour. The wild-type allele produces a blend of yellow and black pigmentation in each hair of the mouse. This yellow and black blend may be referred to as 'agouti' in colour. One of the mutant alleles of the agouti gene results in mice with a much lighter, yellowish colour. When these yellow mice were crossed with homozygous wild-type mice, a 1:1 ratio of yellow and dark grey offspring were obtained. This indicated that the yellow mutation is dominant, and all the parental yellow mice were heterozygotes for the mutant allele.

By mating two yellow mice, Cuénot expected to observe a usual 1:2:1 Mendelian ratio of homozygous agouti to heterozygous yellow to homozygous yellow. Instead, he always observed a 1:2 ratio of agouti to yellow mice. He was unable to produce any mice that were homozygous for the yellow agouti allele.

It wasn’t until 1910 that W. E. Castle and C. C. Little confirmed Cuénot’s work, further demonstrating that one quarter of the offspring were dying during embryonic development. This was the first documented example of a recessive lethal allele.

Recessive Lethals
A pair of identical alleles that are both present in an organism that ultimately results in death of that organism are referred to as recessive lethal alleles. Though recessive lethals may encode for dominant or recessive or traits, they are only fatal in the homozygous condition. Heterozygotes will sometimes display a form of disease phenotype, as in the case of achondroplasia. One mutant lethal allele is tolerated, but having two results in death. Not all heterozygotes for recessive lethal alleles will show a mutant phenotype, as is the case for cystic fibrosis carriers. If two cystic fibrosis carriers have children, they have a 25% chance of producing offspring having two copies of the lethal allele, eventually resulting in the death of the child.

Another example of a recessive lethal allele occurs in the Manx cat. Manx cats possess a heterozygous mutation resulting in a shortened or missing tail. Crosses of two heterozygous Manx cats result in 2 offspring displaying the heterozygous shortened tail phenotype, and 1 offspring of normal tail length that is homozygous for a normal allele. Homozygous offspring for the mutant allele cannot survive birth and are therefore not seen in these crosses.

Dominant Lethals
Alleles that need only be present in one copy in an organism to be fatal are referred to as dominant lethal alleles. These alleles are not commonly found in populations because they usually result in the death of an organism before it can transmit its lethal allele on to its offspring. An example in humans of a dominant lethal allele is Huntington's disease, a rare neurodegenerative disorder that ultimately results in death. A person exhibits Huntington's disease when they carry a single copy of a repeat-expanded huntingtin allele on chromosome 4.

Conditional Lethals
Alleles that will only be fatal in response to some environmental factor are referred to as conditional lethals. One example of a conditional lethal is favism, a sex-linked inherited condition that causes the carrier to develop hemolytic anemia when they eat fava beans.