Lethal alleles

Lecture 4

Prepared bySamira Fattah

Assis. Lec.College of health sciences-HMU

What are Lethal alleles?

– Definition• Genes which result in viability reduction of

individual or become a cause for death of individuals carrying them.

• Some lethal genes cause death of zygote or the early embryonic stage while some express their effect in later stages of development.

• Certain genes are absolutely essential for survival. Mutation in these genes creates lethal allele

• Lethal alleles are dominant or recessive

• Fully dominant lethal allele kills organism in both homozygous and heterozygous condition

• Certain lethal alleles kills organisms in homozygous condition only.

History

• Lethal genes were first discovered by Lucien Cuénot while studying the inheritance of coat colour in mice.

• He expected a phenotype ratio from a cross of 3 yellow:1 white, but the observed ratio was 2:1.

• Allele was lethal in homozygous dominant condition

• Cuénot thus determined that yellow coat color was the dominant phenotypic trait, and by using test crosses, he showed that all his yellow mice were heterozygotes. However, from his many crosses, Cuénot never produced a single homozygous yellow mouse.

• How could this be?

• Shortly thereafter, in 1910, W. E. Castle and C. C. Little confirmed Cuénot's unusual segregation ratios .

• Moreover, they demonstrated that Cuénot's crosses resulted in what appeared to be non-Mendelian ratios because he had discovered a lethal gene.

• Castle and Little did this by showing that one-quarter of the offspring from crosses between heterozygotes died during embryonic development .

• This was why Cuénot never observed homozygous yellow mice! Thus, by considering embryonic lethality, or death, as a new phenotypic class, the classic 1:2:1 Mendelian ratio of genotypes could be reestablished

• As this examples illustrate, lethal genes cause the death of the organisms that carry them.

• Sometimes, death is not immediate; it may even take years, depending on the gene.

• In any case, if a mutation results in lethality, then this is indicative that the affected gene has a fundamental function in the growth, development, and survival of an organism.

Types of lethal genes

• Recessive Lethal Genes

• Cuénot and Baur discovered these first recessive lethal genes because they altered Mendelian inheritance ratios.

• Recessive lethal genes can code for either dominant or recessive traits, but they do not actually cause death unless an organism carries two copies of the lethal allele.

• Examples of human diseases caused by recessive lethal alleles include cystic fibrosis, sickle-cell anemia, and achondroplasia

• Achondroplasia is an autosomal dominant bone disorder that causes dwarfism. While the inheritance of one achondroplasia allele can cause the disease, the inheritance of two recessive lethal alleles is fatal.

• Dominant Lethal Genes• Dominant lethal genes are expressed in both

homozygotes and heterozygotes. But how can alleles like this be passed from one generation to the next if they cause death?

• Dominant lethal genes are rarely detected due to their rapid elimination from populations. One example of a disease caused by a dominant lethal allele is Huntington's disease

• Huntington's disease• a neurological disorder in humans, which reduces life

expectancy.

• Because the onset of Huntington's disease is slow, individuals carrying the allele can pass it on to their offspring. This allows the allele to be maintained in the population. Dominant traits can also be maintained in the population through recurrent mutations .

Conditional Lethal Genes

• an organism lives normally under one set of conditions, but when certain changes are introduced in its environment, lethality results.

• Favism is a sex-linked, inherited condition that results from deficiency in an enzyme called glucose-6-phosphate dehydrogenase.

• It is most common among people of Mediterranean, African, Southeast Asian, and Sephardic Jewish descent .

• The disease was named because when affected individuals eat fava beans, they develop hemolytic anemia, a condition in which red blood cells break apart and block blood vessels.

• Blockage can cause kidney failure and result in death

Sex-Linked Lethal Genes

• Semilethal or Sublethal Genes

• the lethal gene is carried on the sex chromosome, usually X.

• Hemophilia is a hereditary disease caused by deficiencies in clotting factors, which results in impaired blood clotting and coagulation.

• Because the allele responsible for hemophilia is carried on the X chromosome, affected individuals are predominantly males, and they inherit the allele from their mothers.

• The alleles responsible for hemophilia are thus called semilethal or sublethal genes, because they cause the death of only some of the individuals or organisms with the affected genotype.

• Normally, clotting factors help form a temporary scab after a blood vessel is injured to prevent bleeding, but hemophiliacs cannot heal properly after injuries because of their low levels of blood clotting factors.

• Therefore, affected individuals bleed for a longer period of time until clotting occurs. This means that normally minor wounds can be fatal in a person with hemophilia.

Synthetic Lethal Genes• When an allele causes lethality, this is evidence that the

gene must have a critical function in an organism.

• The discoveries of many lethal alleles have provided information on the functions of genes during development.

• So scientists used conditional and synthetic lethal alleles to study the physiological functions and relationships of genes under specific conditions.

Breeding

• Inbreeding• The process of mating of individuals which are more closely

related than the average of the population to which they belong, is called inbreeding.

• Normally, inbreeding is affected by restrictions in population size or area which brings about the mating between relatives.

• Since close relatives have similar genes because of common heritage, inbreeding increases the frequency of homozygotes, but does not bring about a change in overall gene frequencies.

• Thus, a mating between two heterozygotes as regards two alleles A and a will result in half of the population homozygous for either gene A or a and half of the population heterozygous like the parent but the overall frequencies of A and a remain unchanged :

Aa X Aa

1 AA : 2 Aa : 1 aa

• Thus, inbreeding brings about the recessive gene to appear in a homozygous state (aa).

• Once a recessive allele is in a homozygous state, natural selection can operate upon the rare recessives.

• Artificial selection is also possible as the homozygous recessives are phenotypically differentiated from the dominant population.

• Genetic Effects of Inbreeding• The continuous inbreeding results, genetically,

in homozygosity. It produces homozygous stocks of dominant or recessive genes and eliminate heterozygosity from the inbred population.

• The practical applications of inbreeding are following:

1. Because inbreeding cause homozygosityof deleterious recessive genes which mayresult in defective phenotype, therefore, in humansociety, the religious ethics unknowinglyand modern social norms consciously have condemnedand banned the marriages of brothersand sisters.

2.Because inbreeding results in the homozygosity of dominant alleles, therefore, the animal breeder have employed the inbreeding to produce best races of horses, dogs, bulls, cattles, etc.

The modern race horses, for example, are all descendents of three Arabian stallions imported into England between 1689 and 1730 and mated with several local mares of the slow, heavy type .

The fast runners of F1 were selected and inbred and stallions of the F2 appear as beginning points in the pedigrees of almost all modern race horses.

This sort of inbreeding in also called line breeding which has been defined as the mating of animals in such a way that their descendents will be kept closely related to an unusually desirable individual.

• Outbreeding• When a mating involves individuals that are

more distantly related than the average of the selected group it is classified as outcrossing or outbreeding

• Outbreeding involves crossing individuals belonging to different families or crossing different inbred varieties of plants or crossing different breeds of livestock.

• Outbreeding increases heterozygosity.

• and enhances the vigour of the progeny, i.e., hybrid has superior phenotypic quality but often has poor breeding value than the parental populations.

• Cross Breeding and Mule Production

• Mating of individuals from entirely different races or even different species is called cross breeding.

• This represents the most extreme form of outbreeding that is possible among animals.

• Cross breeding produces sterile hybrids in comparison to normal outbreedings.

• A mule is a hybrid of a male donkey (Equus asimus, 2n = 62) and a female horse (Equus caballus, 2n = 64).

• The hybrid from the reciprocal cross (i.e., a female donkey or jenny and a male horse or stallion) is called henny.

EVOLUTIONARY SIGNIFICANCE OF INBREEDING AND OUTBREEDING

• The inbreeding and outbreeding, both, provide raw material to natural selection.

• Inbreeding allows natural selection to operate on recessive genes, but does not permit the introduction of good mutations from outside.

• While, outbreeding provides an opportunity for the accumulation of good traits of different races in one individual or line.

• It expresses good qualities of the races and masked the deleterious recessive alleles.

• Thus, it can be concluded at last that inbreeding and outbreeding, both, provide new allelic combinations which may be good or bad for the natural selection.