Genetic coding of human cells is made up of Deoxyribonucleic acid (DNA). The characteristics of the human cellular system specifies the building block of proteins and molecules of ribonucleic acid (RNA). Nucleic acids are made up of polymers of long chains of monomers repeating themselves over and over. They may be double stranded or single stranded. The monomer of the nucleic acid is the nucleotide. Nucleotides are built containing a phosphate group, a nitrogenous base and a 5-carbon sugar. DNA and RNA contain a sugar compound; DNA contains deoxyribose and RNA contains ribose. There are five different nitrogenous bases found in nucleotides. Adenine (A), Guanine (G), Thymine (T), Cytosine (C) and Uracil (U). (Alberts et al., 1998) Both RNA and DNA are made up of polynucleotide chains which are different in the two molecules. RNA contains the nitrogenous base Uracil (U) and the DNA base contains Thymine (T). RNA and DNA have structural differences with DNA being a double stranded helix and RNA being single stranded. (Kratz,2009)
DNA contains genetic information. The codes that the genetic information contain are ultimately what controls the structure and function of each cell. When the cell needs protein, RNA reads the coding and copies it into the Mrna which gets transferred into the cytoplasm. Coding in Mrna comes in a pattern of the four nitrogenous bases. The length and order of each strand can be different from one to another. The differences in coding of Mrna molecules determines the difference in primary structures. Our DNA coding is constantly being read by cells within the human mechanism, this uses the information to construct proteins to complete the process to complete bodily functions to run efficiently. This intertwined effort is known as transcription and translation. (Kratz,2009)
The human body is made up of 46 chromosomes, 23 from the female and 23 from the male. Genetic diseases can be altered by a faulty set of genes, or a singular faulty gene. Single gene disorders are the absence or altercation of genes or a single gene. These can be inherited by x-linked recessive, x-linked dominant, autosomal recessive and autosomal dominant varieties. Autosomal dominant is present in all generations, the faulty gene is more dominant than the healthy one. Autosomal recessive means the person will have two copies of a faulty gene which can be one copy from the female and one copy from the male. X-linked dominant generally occurs in females, they usually contain one altered copy and one normal copy of a gene that is X-chromosome. X-linked recessive is common in males which is altercation of the X-chromosome. (Betterhealth.vic.gov.au, 2019)
Chromosomal abnormalities can be quite common. There are over a 1000 known abnormalities which can happen when a change in structure of the chromosome alters and can be passed onto the child from the parent. Occasionally during reproduction, the sperm and egg may lose or add a chromosome which will produce abnormalities. Most of the time this will end in a pregnancy breakdown. Mitochondrial disorders can happen when genes in the cell production are altered which affects the production of enzymes and the production of ATP. There are also multifactorial disorders from environmental aspects that can have an effect of disease. This has created increased scientific research into the use of gene therapy.
Genetic revolution has evolved greatly with the gene therapy discovery in the 1980’s. Germ line therapy involves the function of sperm and egg treatment. Modifying the gene so it’s not inheriting the disease or genetic disorder. Genetic material can also be transferred into patients’ cells called somatic gene therapy. Viral vector therapy uses harmless viruses to deliver genes into the human system to reach the cells. There is a large variety of viruses used to do this; retroviruses, Adenoviruses, Adeno-associated viruses (AVVs) and Herpes simplex virus. Non-viral methods include direct DNA injections which evidence has shown to be successful. Other non -viral methods have been used such as sonoporation, electroporation, magnetofection, gene guns and receptor mediated gene transfer. (Misra, 2013)
Cystic Fibrosis is most common in Caucasians. In 1989 the gene cystic fibrosis transmembrane conductance regulator (CFTR) was discovered. Since then, 600 mutations have been found. Since 1989 the scientific advancement of screening programmes, therapeutic approaches, animal models and the biological aspects of the disease are evolving. CFTR gene causes thick mucus to secrete which clogs up and causes lung infections, blockages in the pancreas and causes enzyme denaturation preventing the intestine to function efficiently. The CFTR gene has 5 classes of mutations. These are classified by which mechanism disrupts the function and synthesis of CFTR. The CFTR plasma protein usually transfer ions out of the cells by active transport. When a mutation transpires in the tertiary structure of the CFTR, the protein will fail to reach the plasma membrane. Consequently, the cells build up Cl- and Na+ ions which then are unable to leave the cell. (Porteous & Davidson, 1998) Cystic fibrosis is a genetic inherited disorder which one is born with, the faulty gene cannot be caught later in life. Biological parents must both carry the Cystic Fibrosis gene, giving a 25 percent chance of having the genetic disorder. Also if both parents carry the gene, 50 percent of foetuses carry the gene and 25 percent chance they may not carry it at all. Whilst a female is at a fertile stage in their life and wanting to create a family, carrier screening can be completed before they are pregnant or whilst they are pregnant. This can give the biological parents options to see if they are both carriers. If one was to choose genetic screening, there are two main types. Prenatal genetic tests and screening diagnostics. The latter one can be completed on cells from the placenta or foetus obtained through Chronic villus sampling (CVS) or Amniocentesis. The problem with this screening is it carries a small chance of pregnancy loss. Below Is a picture of the mode of inheritance of cystic fibrosis.
http://www.myvmc.com/uploads/VMC/DiseaseImages/3182_cystic_fibrosis_inheritance.jpg
In February 2018 the FDA approved a new treatment for cystic fibrosis, called Tezacafactor, Ivacaftor (Symdeko). This form of treatment was approved for the most common mutation F508del in humans who have the single copy of the gene. When the CFTR protein is not coded for correctly, the Tezacafactor drug improves the function of that protein. In the late stages of clinical trials, CFTR sufferers who took the combination of the drugs had seen improved lung function by 6.8 percent. Fertility treatment has also evolved with many scientific discoveries from 1989. Most males that have the Cystic fibrosis gene are 98 percent infertile. Medical advances now mean fertility treatment success rates by having the pre-implantation diagnosis (PGD) to ensure a healthy embryo. This form of treatment aims to decrease cystic fibrosis diagnosis within the next decade.
A new experimental approach to Cystic Fibrosis patients was introduced in 2016 called CRISPR/Cas9. This process involves gene editing by replacing the faulty CFTR gene by a correct copy using CRISPR/Cas9 technology. The mode of method involves inserting the Lipid nanoparticle (LNP) or the Adeno-associated Virus (AAV) into the system. This will recognise the faulty sequence and remove it, replacing it with the correct portion of gene sequence.
To conclude, it is evident that more research is needed to find a genetic treatment to cure or improve quality of life by reducing symptoms for cystic fibrosis sufferers. With the current research into molecular biology and improvements of using gene therapy, new discoveries are increasing the link between genetics and inherited diseases. Fertility research has shown promise into reducing the number of cystic fibrosis diagnosis’s, although more research is needed. Recent research from articles has shown the strengths and limitations of this treatment. Strengths include reducing the foetuses’ risk of inheriting a genetic disorder or disease and preventing next generations of having disease too. Limitations of this treatment would include terminations of healthy embryos, foetus which can negatively impact the patient’s emotional wellbeing.
References
Alberts, B., Bray, D., Johnson, A., Lewis, J., Raff, M., Roberts, K. & Walter, P. (1998) Essential cell biology. New York, N.Y: Garland. Citation: (Alberts et al., 1998)
Cohen, B., Wood, D. & Memmler, R. (2000) Memmler’s the human body in health & disease. Philadelphia: Lipplincott Williams & Wilkins. Citation: (Cohen, Wood & Memmler, 2000)
Cutting, G. (2014) Cystic fibrosis genetics: from molecular understanding to clinical application. Nature Reviews Genetics. 16 (1), pp. 45-56.
Citation: (Cutting, 2014)
Kratz, R. (2009) Molecular & cell biology for dummies. Hoboken, N.J.: Wiley.
Citation: (Kratz, 2009)
Misra, S. (2013) Human Gene Therapy: A Brief Overview of the Genetic Revolution. JAPI. 61pp. 41-47.
Citation: (Misra, 2013)
Moore, J. & Langley, R. (2011) Biochemistry for dummies. Hoboken, N.J.: Wiley Pub. Inc.
Citation: (Moore & Langley, 2011)
Porteous, D. & Davidson, D. (1997) Cystic fibrosis lung infection cleared up?. Nature Medicine. 3 (12), pp. 1317-1318.
Citation: (Porteous & Davidson, 1998)
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