3. LETHAL ALLELES Compiled by Siti Sarah Jumali Level 3 Room 14 Ext 2123

LETHAL ALLELES Alleles that cause an organism to die only when present in homozygous condition, where the gene involved is an essential gene. Instead of mutations alter the appearance of a living organism, a mutant allele could cause death. When an essential gene is mutated, it can result in a lethal phenotype. If the mutation is caused by a dominant lethal allele, the heterozygote for the allele will show the lethal phenotype, the homozygote dominant is impossible. If the mutation is caused by a recessive lethal allele, the homozygote for the allele will have the lethal phenotype. Most lethal genes are recessive.

What is it? Lethality refers to Genome changes of an organism which produce effects severe enough to cause death. Lethality is a condition in which death of a certain genotype occurs prematurely. Fully dominant lethal allele kills the carrier in both homozygous and heterozygous conditions. Occasionally arises by mutation from a normal allele. Completely lethal genes usually cause death of the zygote, later in the embryonic development or even after birth or hatching. Complete lethality, thus is the case where no individual of a certain genotype attain the age of reproduction. However, in many cases lethal genes become operative at the time the individuals become sexually mature. Such lethal genes which handicap but do not destroy their possessor are called subvital, sublethal or semilethal genes. The lethal alleles modify the 3: 1 phenotypic ratio into 2 : 1.

Many lethal alleles prevent cell division –These will kill an organism at an early age Some lethal alleles exert their effect later in life –Huntington disease Characterized by progressive degeneration of the nervous system, dementia and early death The age of onset of the disease is usually between 30 to 50 Conditional lethal alleles may kill an organism only when certain environmental conditions prevail –Temperature-sensitive (ts) lethals A developing Drosophila larva may be killed at 30 C But it will survive if grown at 22 C

Semilethal alleles –Kill some individuals in a population, not all of them –Environmental factors and other genes may help prevent the detrimental effects of semilethal genes A lethal allele may produce ratios that seemingly deviate from Mendelian ratios An example is the “creeper” allele in chicken –Creepers have shortened legs and must creep along –Such birds also have shortened wings –Creeper chicken are heterozygous

DOMINANT LETHAL ALLELES Modifies 3:1 ratio to 2:1 Organism die before they can produce the progeny. So, the mutant dominant lethal allele is removed from the population in the same generation it arose Fully dominant lethal allele kills the carrier in both homozygous and heterozygous conditions.

DOMINANT LETHAL ALLELES CONT’D Lethal allele segregation A 2:1 ratio among the progeny of a cross results from the segregation of a lethal allele. © 2005 W. H. Freeman Pierce, Benjamin. Genetics: A Conceptual Approach, 2nd ed. (New York: W. H. Freeman and Company), 105. Used with permission. All rights reservedW. H. Freeman

Example Huntington's disease - although it is not described as lethal, it is invariably lethal in that the victim experiences gradual neural degeneration and mental deterioration for some years before death occurs.

The Pedigree

RECESSIVE LETHAL ALLELE The recessive lethal allele kills the carrier individual only in homozygous condition. They maybe of two kinds (i) one which has no obvious phenotypic effect in heterozygotes and (ii) one which exhibits a distinctive phenotype when in heterozygous condition. Occasionally arise from normal allele mutation In many cases, lethal genes become operative at the onset of sexual maturity

examples Duchenne muscular dystrophy, cystic fibrosis, or Tay-Sachs disease, sickle-cell anemia etc Cystic fibrosis-due to a poorly functioning Cl- ion transport protein in the lungs Tay-Sachs disease- due to an enzyme which is unable to breakdown specific membrane lipids many other lethal alleles are so lethal that the offspring die as embryos

Other examples One coat color of ranch foxes - caused by recessive lethal gene. -This gene causes a death if both recessive alleles are possessed by the same individual.

RECESSIVE LETHAL ALLELE