Lethal Alleles are gene mutations that hamper the survival of an organism. They can present as various genetic disorders which are fatal to the individual. They are identified with the help of techniques such as gene mapping, molecular genetics, genetic crosses, and so on. Identifying them is essential to be prepared with a perfect treatment strategy to fight the upcoming disorder.
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Lethal Allele Definition
Lethal alleles are those alleles that cause the organism that carries them to die. Usually, they are caused by mutations in genes vital to development or growth.
What are Lethal Alleles?
Gene variants that are present in combinations resulting in the death of an organism are lethal alleles. The gene combinations can be homozygous (identical alleles) or heterozygous (unidentical alleles). The lethal alleles usually disrupt the essential functions of an organism which leads to severe developmental abnormalities.
Also Read: Homozygous and Heterozygous Allele
Lethal Allele Examples
The examples of Lethal Allele are as follows:
- Recessive Lethal Alleles: Human illnesses such as achondroplasia, sickle-cell anaemia, and cystic fibrosis are examples of recessive lethal alleles.
- Dominant Lethal Alleles: One of the best examples of dominantly lethal alleles in humans is Huntington’s disease.
- Conditional Lethal Alleles: Favism is a genetically fatal disorder. When a carrier of this sex-inherited disorder consumes fava beans, they get hemolytic anaemia.
- Semi-lethal dominant Lethal Alleles: The creeper trait, which causes shorter legs in chickens, is a semi-lethal dominant allele.
Types of Lethal Allele
Lethal Alleles are classified into the following types:
- Recessive Lethal: Most of the lethal alleles are recessive. Only in the homozygous combination, do the lethal genes show up when an individual inherits two copies of the recessive lethal allele. In heterozygotes, the survival is usually unaffected by the physical factors. When the dominant allele is recessive lethal, it leads to homozygous embryos that do not survive from the early developmental stage.
- Dominant Lethal: Dominant lethal alleles have to show their presence at least in one entity to be deadly. They occur very rarely as the entity does not survive longer to pass it through their generations. For example, Huntington’s disease has dominant lethal alleles. It is a neurological condition leading to death.
- Conditional Lethal: Alleles that show their lethality only under certain conditions or situations are termed conditional lethal. For example, a particular temperature can manifest the fatal behaviour of an allele (usually high temperature). It is not only the temperature that can influence the fatal functions, food, light, and other factors also impact them.
- Balanced Lethal: When two individually lethal alleles in a homozygous state are maintained to ensure their presence in a heterozygous state, this phenomenon is termed a balanced lethal system and the alleles involved are balanced lethal alleles. Individuals carrying a copy of a lethal allele in a heterozygous condition can survive. If an individual inherits two copies of any one of the lethal alleles in a homozygous condition, it is difficult to survive, and it’s fatal. For example, Fruit flies.
- Gametic Lethal: Gametic lethal alleles are those that prevent gametes from fertilising. It follows a mechanism that causes the generation of an unequal number of gametes in a heterozygote. This is called meiotic drive.
Causes of Lethal Alleles
Lethal Alleles are usually caused due to gene mutations that are involved in the development of an organism. These mutations can lead to disturbances in the functionality of the proteins which disrupt the biological processes. Below are the mechanisms through which lethal alleles arise:
Gene Mutations
- Splicing mutations (mutations that affect the splicing of mRNA) produce abnormal proteins that disturb cellular functions.
- Frameshift mutations (deletion or insertion of nucleotides in a gene) produce a nonfunctional protein that causes lethality.
Altered Gene Regulations
Mutations that occur in the regulatory regions of a gene that affect the gene expression can alter the levels of certain proteins that might be essential for the survival of the individual.
Identification of Lethal Alleles
Predicting the presence of a lethal allele can be easier with the help of the following methods:
- Genetic Crosses: Genetic crosses between individuals with known genotypes can help in the identification of lethal alleles. By observing the outcomes of the crosses, the presence of a lethal allele can be understood based on the inheritance pattern.
- Analysis of Offspring Ratios: Lethal alleles result in an altered phenotypic ratio. It can be better understood with the help of the following example, if a lethal allele is present, a reduced frequency in the presence of that allele (in homozygous individuals) can be seen. Deviations from the expected ratios can indicate lethal allele presence.
- Molecular Genetics: Modern techniques in molecular genetics such as DNA sequencing and PCR (polymerase chain reaction) can help in analysing the individual’s DNA and the associated mutations. The genetic basis of the fatality or lethality can be revealed by comparing the DNA sequences of individuals with the presence or absence of a lethal phenotype.
Effect of Lethal Alleles on Various Populations
The effect of lethal alleles can vary depending on various factors such as the allele nature, the size of the population, and the mode of inheritance. The following are a few general effects:
- Reduced Fertility: If the lethal alleles are prevalent in populations, the fertility and viability of the individuals are often reduced. Individuals carrying two copies of a lethal allele may not survive until reproductive age which leads to a decrease in the overall population.
- Genetic Drift: Genetic drift has an important impact on the frequency of lethal alleles. Random fluctuations in the frequencies of alleles due to genetic drift can result in the fixation or loss of lethal alleles that affect the genetics of the overall population.
- Genotypic and Phenotypic Ratios Alteration: The expected Mendelian genotypic and phenotypic ratio can be deviated due to lethal alleles. The presence of fewer individuals with homozygous genotypes results in an altered frequency distribution.
- Balancing Selection: The presence of two lethal alleles creates a balanced lethal system that leads to the persistence of both lethal alleles at a stable frequency.
- Evolutionary Dynamics: Significant reduction in the lethality reduces the fitness of individuals, which eliminates the allele over time.
Diseases Due to Lethal Alleles
Following are the genetic disorders that arise due to lethal alleles which result in early death and major challenges:
- Tay Sachs disease: It is an autosomal recessive disorder that is caused by to HEXA gene mutation. It leads to the accumulation of gangliosides in the central nervous system. They experience neurodegeneration and problems in early development.
- Cystic Fibrosis: CFTR gene mutations cause cystic fibrosis. The protein CFTR is involved in the transportation of ions across the membranes. It affects the reproductive, respiratory, and digestive systems.
- Achondroplasia: Mutations in the FGFR3 gene lead to the autosomal dominant disorder called achondroplasia that results in complications like decreasing the lifespan of an individual.
- Huntington’s Disease: It is an autosomal dominant disorder caused by a mutation in the HTT gene. It produces a toxic huntingtin protein that causes neurodegeneration increasing the risk of fatality.
- Osteogenesis Imperfecta Type 2: It is a group of disorders that are identified by the presence of brittle bones due to the mutations of COL1A1 and COL1A2 genes that lead to skeletal abnormalities.
Conclusion – Lethal Allele
The importance of the lethal alleles has to be understood as they have negative implications for human populations. Arising due to genetic mutations, they result in several life-threatening disorders. While the lethal genes are busy challenging survival, they also contribute to the genetic architecture and evolutionary processes understanding. With advancements in the studies related to genetics, the hope to mitigate the effect of lethal alleles is also increasing.
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FAQs on Lethal Allele
What is a Lethal Allele?
A lethal allele is a gene variation, that leads to the death of an organism when present in a homozygous state. They are caused mostly due to mutations.
How are Lethal Alleles classified?
Lethal alleles can be classified based on the mode of inheritance, underlying molecular mechanisms, phenotypic effects, gene specificity, and frequency.
What are Lethal Alleles and Essential Genes?
Lethal and essential genes play a crucial role often carrying out the opposite functions. Essential genes help in the survival and development of an individual whereas lethal genes promote death.
How is the Inheritance pattern Affected due to Lethal Alleles?
Lethal alleles hamper the expected genotypic-to-phenotypic ratio of the offspring. For example, a heterozygous lethal allele carrier may be normal while its effects can be seen in offspring.
Can Lethal Alleles be Detected?
Lethal alleles can be detected with the help of gene mapping, gene expression studies, molecular genetics techniques, and genetic crosses. It helps in treating the diseases.
How can you tell if an Allele is Lethal?
Lethal alleles might be autosomal, sex-linked, dominant, or recessive. Both homozygous dominant and heterozygous individuals will perish if the allele is dominant.
What Causes a Lethal Allele?
Lethal allele it is the consequence of gene-mutation that is required to grow and develop.