Genetic testing is the analysis of human DNA, RNA, and chromosomes in order to detect heritable disease mutations, genotypes, and phenotypes for clinical use. The purpose of genetic testing is to diagnose genetic diseases in newborns, children, and adults and to identify the future health risks. The diseases I will be mentioning in this essay are: sickle cell anaemia, MCAD, and Huntington disease. (10)
Sickle cell disease is an inherited, autosomal recessive disorder known also as sickle cell anaemia which is found in a homozygous form, the most serve. Sickle cell disease is a disorder of the haemoglobin in which the β subunit genes have a missense mutation that removes the amino acid valine for glutamic acid at amino acid 6.The protein haemoglobin is composed of four subunits, two alpha subunits and two beta subunits. The alpha subunits are encoded by HBA on chromosome 16 and the beta subunits are encoded by the HBB gene on chromosome 11. This mutation causes the β-globlin to decrease the solubility of deoxygenated haemoglobin causing to form a gelatinous network of fibrous polymers distorting the red blood cell forming a sickle shape. It was first discovered in 1949 that sickle cell anaemia is inherited as a Mendelian trait it was first discovered by James Neel, and E.A Beet. Linus Pauling also made a discovery; he discovered that haemoglobins that are isolated from diseased and normal individuals would differ in their rates of haemoglobin. The aim of his experiment was to see if there was a difference in normal and sickle cell haemoglobin. The results of the hypothesis showed all molecules moved towards the anode, this indicated a net negative charge. However, Haemoglobin A migrated further than haemoglobin S this suggested the net charge was greater. The results from the electrophoresis showed carriers had both HbA and HbS. People with sickle cell have atypical haemoglobin molecules called haemoglobin S; this molecule distorts the red blood cells into sickle shape. The disease sickle cell affects millions of people worldwide; it is common among people from Africa. Sickle cell disease is caused by mutations in the HBB gene. The HBB gene makes a protein called β-globlin.The gene of this disease causes sickle cell anaemia. Mutations in the HBB gene results in the production of haemoglobin S. In sickle cell anaemia the haemoglobin S replaces both β-globin subunits in haemoglobin. This mutation changes the amino acid glutamic acid to valine at position 6 in β- globin. The mutational change cause the haemoglobin S to stick together to form rigid molecules. The production of rigid molecules bends the red blood cells into crescent shapes. A method of genetic testing for sickle cell anaemia is restriction fragment length polymorphism (RFLP) analysis. Prenatal diagnosis is done on sickle cell anaemia. The single nucleotide substitution removes a cutting site in the β-globlin gene for restriction enzymes MstII and CvnI. This results in the mutation altering the pattern of restriction fragments which can be seen on southern blots. These differences in the restriction cutting sites are used to prenatally diagnose sickle cell anaemia. Testing adults using this analysis requires blood samples and DNA from white blood cells. RFLP is carried out on cheek cells and collected by swabbing the inside of the mouth. Prenatal diagnosis is the testing of the fetus. Sickle cell anaemia is one of the diseases screened using this method. The following amniocentesis, chorionic villus sampling, and fetal blood sampling are methods used in detecting mutations in single gene disorders by enriching fetal cells from maternal blood by magnetic cell sorting followed by the isolation of fetal cells by micro dissection. (1)(2)
Get your grade
or your money back
using our Essay Writing Service!
Figure1. The location of HBB gene of sickle cell anaemiaThe HBB gene is located on the short (p) arm of chromosome 11 at position 15.5.
The HBB gene can be found on the short arm of chromosome 11 at position 15.5 from base pair, 246,695 to base pair 5,248,300.(11)
Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is an inherited defect in the beta-oxidation of fatty acids with autosomal recessive inheritance. This means both copies of the gene have mutations. The parents of an individual with an autosomal recessive condition each carry a copy of the mutated gene, but don't show the symptoms of the condition. In humans it is the most frequently diagnosed defect of mitochondrial β-oxidation. MCAD can occur anytime in life from neonatal phase to adulthood. The majority of individuals with this defiency are present with metabolic crisis during the first years of life when metabolically challenged by fasting/or viral illness. The symptoms of this defiency include coma, hypoketonic hypoglycemmia, and death. Statistics show 20% of patients die during their first metabolic crisis. In contrast patients using the treatment regimen that avoids fating and low diets has been seen to reduce and elimate recurrent disease episodes. It has been found out that the majority of patients around 80% with MCAD defiency are homozygous for a common mutation, 985A→G and another 18% have this mutation in one disease allele. At present no further mutations have been identified, but a great amount of mutations have been detected and characterized with MCAD defiency. MCAD is caused by a mutation in the ACADM gene. The gene provides the key to making the medium chain acyl coenzyme. The dehydrogenase breaks down the group of fats called medium chain fatty acids. 80 mutations have been found in this gene to cause this defiency. Most of the mutations have been found to change a single amino acid in the MCAD enzyme. This causes an alteration of the enzymes structure and reduces its activity. A defiency in the MCAD enzyme leads to medium chain fatty acids not functionaling properly. This results in fats not being converted to energy this leads to lack of energy and low blood pressure. Medium chain fatty acids can build up in the tissues and can damage the liver and the brain. This build up causes the symptoms of MCAD defiency. (3)(6)(7) Newborn screening is a genetic test that analyzes infant blood samples for abnormal or missing gene products such as proteins. For example, infants are screened for medium chain acyl coenzyme dehydrogenase, a metabolic disease in which an enzyme deficiency can cause a defect of mitochondrial β-oxidation of fatty acids.(10)
Always on Time
Marked to Standard
Figure2.The location of the ACADM gene.
The ACADM gene is located on the short (p) arm of chromosome 1 at position 31.
The gene is located on the short arm of chromosome 1 at position 31 from base pair 76,190,042 to base pair 76,229,354 on chromosome 1.(7)
Huntington disease (HD) is inherited as an autosomal dominant disorder affecting 1 in 10,000 people. It is a progressive neurodegenerative disorder caused by mutations in the HD gene. It occurs in adult onset and appears in an individual in their thirties and forties. Symptoms of this disease include depression, irritability, and poor coordination; these symptoms appear in the fifth decade of life. As the disease progresses on in adult onset the individual may experience trouble walking, speaking, and swallowing. Patients with this form of disease live to around 15-20 years after symptoms begin. Another form of Huntington's disease is an early onset, this begins in childhood. The Huntington disease is located on the short arm of chromosome 4. It was the gene to be mapped using restriction fragment length polymorphism. Mutations in the HTT gene cause Huntington's disease. The gene encodes a protein of 35 KDa called huntingtin (HTT). This protein plays an important role in nerve cells in the brain and is important in the development before birth. One region of the gene contains a DNA segment known as CAG trinucleotide repeat. This region is made up of the bases cytosine, adenine, and guanine that appear multiple times in a row. The inherited mutation causing Huntington disease is known as a CAG trinuclotide repeat. Normal individuals have 7 to 34 repeats. People with the disease have 36 to 12 CAG repeats. Individuals with 36 to 40 CAG repeats may or may not develop the symptoms of Huntington's disease, but people with more than 40 repeats develop the disorder. People with the adult onset form of Huntington disease has around 40-50 CAG repeats in the HTT gene, in contrast people with early onset form of the disorder have more than 60 CAG repeats. As the HTT gene is passed from generation from parent to child the size of the CAG trinucleotide repeat increases in the range associated with Huntington disease. Huntington's disease is a class of inherited neurodegenerative disorders that are characterized by the expansion of CAG repeats within exons, resulting in polyglutamine tracts in the encoded proteins. The polyglutamine diseases are inherited as dominant traits with symptoms appearing in adult onset. (4)(5)
Figure 3. The location of HTT gene
The HTT gene is located on the short (p) arm of chromosome 4 at position 16.3.
The HTT gene is located on the short arm of chromosome 4 at position 16.3 from base pair 3,076,407 to base pair 3,245,686.(4)
Genetic tests to confirm the diagnosis of Huntington's disease have been done using blood samples. The genetic test looks at the DNA for HD mutations this is done by counting the number of CAG repeats in the huntingtin gene. Presymptomatic is a predictive testing it is used to test whether family member s are at risk for genetic conditions present in the family. This test can be done for on individuals with huntington's disease .Deciding to be tested for Huntington's disease and the other diseases mentioned can be difficult for an individual. Genetic counsellors can help individuals make the difficult decisions about testing easier for them. (9)
To conclude genetic testing is helpful in diagnosing a disease in an individual with symptoms and to help minimize the risk of developing a disease.