Molecular Biology

Question: Discuss about thee disease associated with genes due to mutation? Answer: Mutation: Molecular biology relates the activity of biomolecules in various cellular systems which include the interaction of DNA, RNA, and Proteins in different biosynthesis pathway. Any miscommunication between the molecules may lead to mutation and genetic diseases. Mutation is the permanent change in the nucleotide sequence of a particular genome. The mutation appears from the damage of DNA replication. DNA comprised of nucleotide sequences of adenine (A), guanine (G), thymine (T), and cytosine (C). DNA produces two identical DNA replicas from one DNA during replication. DNA replication is a semiconservative process in which one strand of DNA synthesizes continuously (Leading Strand) and another strand synthesized in a discontinuous manner (Lagging Strand). During the replication, it is possible that the enzymes of the replication machinery can put the wrong nucleotide in some places due to lack of proofreading activity of the enzyme. This may lead to the consequences of mutation (Baer, 20 14). After replication, the DNA undergoes transcription process where genetic information from DNA transcribed into RNA with the help of DNA polymerase and transcription machinery. RNA has nucleotide uracil (U) instead of cytosine, and it contains exact genetic information to translate a protein in ribosomes. So any disincorporation of genetic data can result in dysfunction of protein which may lead to genetic disorders. Protein is comprised of a specific sequence of amino acids. Each amino acid has specific genetic triplet codes that ensure its sequence during translation. The protein is synthesized from mRNA, which is the modified version of nascent RNA comprised of only the exon part, excluding the intron. It is possible that some portion of the nucleotide may get delete during splicing of intron portion. The changes in the nucleotide sequences may produce observable changes in an organism or not. Mutation plays a vital role in the changes in functions of genes. There is various type o f mutations that results in the proper or improper biological phenomenon regarding immune system, cancer, and developmental biology. Mutation does not always result in bad effect. Various changes in DNA happen very often, but not always it leads to any disease or cause death. Mutation generates new variation that sometimes gives an individual survival advantage over other. The main concept of mutation is it creates the difference. Some types of mutation are- Substitution mutation- In the case of this one mutation base is exchange another base. Change in one chemical letter changes the whole genetic triplet codon which results in incorporation of wrong amino acid in protein. However, changes in amino acid codon sometimes create a stop codon results in the incomplete protein (Allison, 2012). Deletion mutation- This kind of mutation related to deletion of one base or a set of bases from the DNA. Deletion of chromosome 22 can result in heart defects immune disease. Insertion Mutation- In this type of mutation extra base pairs is inserted in the DNA stretch. The number of bases can vary from one to thousands. Insertion of more nucleotides disrupts the reading frame which leads to the altered amino acid sequence during translation. Huntingtons disease is an example of inserted trinucleotide repeats (Allison, 2012). Disease associated with genes due to mutation: When abnormalities in the gene lead to the occurrence of disease, it termed as a genetic disease. These kinds of diseases are rare and occur in one person compare to thousands. Genetic diseases sometimes may be heritable. When a particular gene is responsible for such disorders, it refers to single gene diseases. As a result, the protein that the gene produces either synthesized in a high amount or stop producing. Some of the diseases associated with gene are- ADA (Adenosine deaminase deficiency)- A rare but dangerous disease of gene disorder that associated with the disorder in the immune system. It occurs with a mutation on chromosome 20. The amino acid alanine replaces glycine at 282th position of the chromosome. This disease restricts the synthesize of the enzyme adenosine deaminase enzyme. Without the enzyme, the toxin particle accumulates and destroys the immune cells. The enzyme deficiency results in increased level of S-adenosylhomocysteine which is toxic to lymphocytes. Individuals with this disease become susceptible to almost all kind of disease such as respiratory system, skin diseases. Babies born with this kind of disorder even die within few months of birth. Cystic Fibrosis- This genetic disorder affects the exocrine glands. The liver is highly affected in this case. Difficulties in the digestion of fats and proteins occur due to cystic fibrosis. The chromosome 7 responsible for the disease makes it an autosomal recessive one. The mutation occurs at the 508th position of cystic fibrosis transmembrane conductance regulator gene. Cystic fibrosis affects the sweat glands resulting in excessive salt excretion which disrupts the mineral balance of the body. The major sign of cystic fibrosis is the salty tasting of skin with poor growth. In severe cases, the vas deferens of the male body can be damaged forever (Allison, 2012). Sickle-cell disease- As stated by Baer (2014), it is a severe hereditary anemic disease. The shape of the red blood cells distorts due to the mutation in chromosome 11 of hemoglobin beta gene. The mutation replaces glutamic acid with valine in the 6th Due to the change in the amino acid, individual suffers from low oxygen supply as valine is hydrophobic in nature. The oxygen supply declines because the altered hemoglobin-S stick to each other and aggregates in the blood. This condition occurs when the person inherits two abnormal copies of hemoglobin gene from the parents. MSUD (Maple Syrup Urine Disease)- It is also an inheritable disease. It associated with a defect in one of three genes. Individuals with this disorder cannot break down leucine, isoleucine, and valine amino acids. High level of leucine consumption can result in mental disability. Individual with MSUD may damage their brain during physical stress. The main symptom of the disease is the smell of urine that smells like maple syrup with increased level of ketone body and excess level of acid in the blood. The single gene disorder can be treated with Gene therapy. It is a technique used by doctors instead of using surgical operation or drugs. This technique uses particular genes and transfers it into the body via vector system to treat the disordered gene. However, one major problem with gene therapy is the lack of availability of proper vector system. References: Baer, C. (2014).Mutation Allison, L. (2012).Fundamental molecular biology, 2e. Hoboken, NJ: Wiley.