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.Types of lethal alleles * Lethal alleles falls into four categories. 1. Early onset- lethal alleles which result in death of an organism at early stage of life for example during embryogenesis 2. Late onset- lethal allele which kills organism at their final stage of life are known as late onset allele 3. Conditional- lethal allele which kill organism under certain environmental conditions only. e.g., temperature sensitive alleles kills organism at high temperature. But they don’t kill any organism at low temperature.Cont.. 4. Semi lethal — Lethal allele which kill only some individuals of the population but not all are know as semi lethal.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 homozy gous 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? P generation Yellow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 .Huntington's Disease Allele D d Allele Genotypes DD Dd and dD dd Homozygous Heterozygous Homozygous Phenotypes Affected Unaffected Dominant Recessive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. * Itis 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 “Carter” bhother ana Femmes Withont Hemephitia hemophilia are thus called semilethal or sublethal genes, because they cause the death i. > of only some of the individuals or organisms with the ee inrenn Se, oe, i ot @ Daughter Daughter {camer for te (does not carry hemophita) hesaphin gene) menace seas gene) xY affected genotype. Children* 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. pt ioe an |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.