Give a brief account of the technique and applications of isoelectric focusing (IEF) in human genetics. Include a discussion as to its accuracy.
Isoelectric focusing separates proteins based on a calculation of their electrical charge differences. A molecule’s charge’s change enables the type of zone electrophoresis to take advantage of this aspect. A molecule’s charge changes as a result of differences in the PH and the surroundings of it. A protein in the PH region below the Isoelectric point will be psoitively charged and migrate towards the cathode but continue to lessen its protein substance throughout this process. This is because the protein will have to reach its PH region that is compatible wih its isoelectric point. The idea is thus that a property of proteins can be used as they are determined by the PH of their local environments which has been a notion of interest in human genetics. The fact that proteins carry a combination of positive, negative and zero net chage, depending on the direct aspects of the PH of their environment ,has also served to increase the interest of researchers to the possibilites available in furthering the theory of isoelectric point in human genetic development. [1]
Human genetics studies and contributes to the process of PI through a modification of the isoelectric point of molecules within an enzyme which enables the cell to transfer the molecules of the enzyme between various sides of its own cell interior thereby regulating and impacting the biochemical procedures of the body. Being able to control the procedure through genetic enhancements makes it possible for researchers to interefere directly in the biochemical functioning of an individual. [2]
Isoelectric focusing has correctly enabled the processment and discovery of a new and stronger type of cell, the eukaryotic cells whose magnitude in comparison with other cells is much stronger and enhanced enabling thereby a more focused control of the biochemical process of the body. The findings seem to point out towards the effectiveness of PI in genetical research and enhancements but more needs however to be said about the accuracy of PI methods conducted by researchers.
How accurate can the process of determining the isoelectric points of some proteins and a peptide by capillary isoelectric focusing is thus the proper question to ask after the aforementioned about its definition and benefits. The evaluation of the accuracy of isoelectric points through capillary isoelectric focusing is enabled through the observation of the PI values of nine proteins and a peptide. In this way and through having priorly determined the PI values with the usage of markers, the accuracy of isoelectric focusing is brought more to realization. The PI values have to be consistent and this is also examined in the determination of this.[3]
2) Discuss the genetic basis, diagnosis, prognosis and treatment of phenylketonuria.
Phenylketonuria (PKU) is an an autosomal recessive genetic disorder that is mainly inherited and manages to increase the levels of a subsance with the name of phenylalanine which exists in the blood. Phenylalanine itself is a combination of blocks of proteins and can be found in certain artificial sweeteners. Phenylketonuria leads thus to the accumulation of this substance which can result in negative impacts on the body’s functioning. Among the direct and most frequent dramatic impacts of PKU on the body are intellectual disabilities and other threatening and harmful health problems that could change the way the system of a person functions.[4] It is therefore very crucial to have the disorder properly diagnosed and treated.
The disagnosis of PKU is based on the observation of certain signs and patterns in the manner the body functions and responds to specific forms of stimulation and tests. PKU itself varies from between the severe form and the milder type of the disorder and each has its own specific symptoms. The most severe form of PKU is known as classic PKU and is complicated to observe in infants since it generally appears only when they are already a few months old. The improper treatment of the disorder in these children, as a result of inappropriate or wrong disagnosis , can lead to permanent intellectual disability transforming what could have been a healthy child into a permanently handicapped individual. Older people who do not receive the appropriate treatment sustain higher and unhealthy levels of phenylalanine which is thus a very dangerous substance if found in unsuitable amounts in the body. [5]
PKU can be diagnosed in children through the observation of the skin and hair color that usually tends to be much lighter among those impacted. This is especially evident through a genetic comparison with other family members. PKU impacted individuals, especially children, tend to also have skin disorders such as eczema. Generally, the children with the less severe form of PKU can also be diagnosed through observation of weight, that is usually lighter with infants or kids impacted, and an analysis of growth that tends to be slower in comparison with other family members. Heart problems and abnormally small head sizes, a case referred to as microcephaly, as well as disorders in behavior and the development of emotional problems, are all symptoms that help in the identification of PKU, whether severe or mild. and aid thus in the treatment of this specific disorder.[6]
The less severe form has a decreased chance of causing brain damage. Those impacted do sometimes not require, in contrast to individuals with the classic and more advanced form of PKU, to remain on a low-phenylalanine diet. The diet is one of the forms of treatment of the disorder and attempts, evidently and reasonably enough, to reduce the substance that is causing the blocks of protein accumulation in the blood.
The genetic basis of PKU is related to the PAH gene that enables the making of an enzyme called phenylalanine hydroxylase which in its turn converts the amino acid phenylalanine and transfers it to other parts of the body. Gene mutations that lead to reduction in the phenylalanine hydroxylase cause phenylalanine to be processed ineffectively and since the brain cells are generally programmed to detect the levels of phenylalanine very sensitively and awarely, brain damage risk increases. It is in this way that the genetic basis of PKU manages to bring about harmful and permanent disorders in the brains of those unfortunate enough to suffer from the disease.[7] The question that remains however to be answered is how is PKU genetically inherited and what can be done about it?
PKU is inherited in an autosomal recessive manner which simply means that both copies of the gene in the body cells have mutations. Though the parents and family members of the person impacted might have the same mutated gene they do not have the condition as they simply do not have both of the copies of the gene in their cells mutated.
Treatments include the aforementioned diet to reduce the phenylalanine levels. This is done by an exprienced team of professionals at a medical center. Infants who are thought to have phenylketonuria are first evaluated by a profssional experienced in the procedure of assessing this specific disorder. Dietary therapy is generally the most widely used method to deal with this illness but has to be carried out with considerat thought to both the psychological and physiological impacts it could have on the individual which is exactly why professional help and assisatnce is required throughout.[8]
3) Discuss the genetic basis, diagnosis, prognosis and treatment of galactosemia.
Galactosemia is a certain type of disorder that is a fairly uncommon form of a genetic metabolic disorder which impacts an individual’s capacity to metabolize the sugar galactose within his body in the most normal and proper way for its effective functioning. The disorder is detected through the observation of the autosomal recessive mode of inheritance which simply means the enzyme responsible for the incorrect galactose regulation is detected especially through the analysis and spotting of galactose degradation.[9]
Galactose deficiency can lead to nagative impacts on the metablism. Though very rare it still has managed to attract the attention of professionals and researchers who have since then identified several methods and tests through which to diagnose the disease. Thereby, though rare infants are currently routinly screened in the United States for the possibility of having the disorder that is only found in one out of 60.000 infants. [10]
The symptoms of the disorder help in identifying it. Tiredness, vomiting, diarrhea and jaundice are all common symtpoms of galactosemia. The test that has also been developed to disagnose it, a blood test from a very specific part of the body, the heel of the infant, is another disagnosis method. Urine tests which analyze the types of enzymes found are also common. Generally doctors try to look at the presence of certain enzymes which transfer and change galactose sugar in milk into energy needed for growth and living. [11]
Galactosemia is a serious condition which makes the fact that it is rare a very fortunate one. A person suffering from this disease cannot consume galactose without harming himself even permanently. Proper disagnosis is thus important in preventing this from happening which is why the routine baby screening for the disorder in the United States, is a healthy and well-thought of procedure.
The genetic basis of galactosemia is in the galactose-1-phosphate uridylyltransferase or simply put the GALT gene which causes inability to produce effectively working enzymes needed for the further metablisation of galactose. This leads to high and toxifying levels of galactose that can have life threatening consequences. Infants are especially vulnerable to galactosemia and die at the stunning rate of 75% if not properly handled through the most common treatment method that involves the elimination of lactose and galactose from the diet. The side effects of galactosemia such as speech disorders and problems or learning difficulties can also be treated more directly. Infants who have been diagnosed with the condition are not breast fed as that contains lactose but are treated and fed with soy-based milk. [12]
5) Give an account of the technique and purpose of chorionic villus sampling. How safe is this procedure and what are the risks involved in this procedure?
Chorionic villus sampling (CVS) is a prenatal test used to diagnose the presence of any genetic disorders in the fetus. This is done through the observation of chromosomal or genetic abnormalities in the fetus. The technique, purpose and risks of it require further analysis as it has become a test of growing importance and popularity among pregnant women. [13]
The purpose of Chorionic villus sampling has already been clarified. The test could shed light on the presence of any disorders in the unborn child. CVS is conducted around 10 to 13 weeks after the last period of the woman which hence means efficiency and punctuality are very important for accurate results. Women who carry a certain mutated gene or have a higher risk of passing a certain genetic disorder through to their child find the test very beneficial. Thereby, mothers who are over the thirty-five years old, have shown strange first trimester screen results or other weird ultra sound evidence, are also known to conduct the test whose purpose would serve to eliminate doubt and enable proper and very early assessment of the disorder in the infant which also simply means that the chance of effective treatment becomes higher.[14]
CVS is performed through the cervix or through the abdomen. The professional conducting the CVS will use an ultrasound first to determine the most suitable approach: the cervix or the abdomen. The technique through which the first type of test is performd is done by inserting a thin plastic tube through the vagina and cervix in order to have access to the placenta. The ultrasound images are again employed to help the professional guide the tube in the proper direction. The placenta is important as it is analyzed later on. The tube extracts a small portion of the chorionic villus tissue. The transabdominal test is done with the usage of a needle that is also inserted through the abdomen and uterus and again into the placenta. The ultrasound images are also employed in this technique which is again similar to the first because of its extraction of another portion of tissue. The amounts of extracted substance with the usage of the two methods, are then analyzed. The DNA, enzymes and chromosomes are after that studied in the samples collected. Abnormalities are generally accurately observed which makes CVS a very reliable test. The results of the test will nevertheless take around a week or two to get to the patient as the findings have to be fully accurate and require thus very meticulous and time-cnsuming analysis. [15]
The risks of CVS can include bleeding, infection, miscarriage (which happens at a rate of 1 in a 100 to 200 cases) and rupture of membranes. The risks become more serious when excessive bleeding is observed in addition to excessive vaginal discharge and fever. CVS could also impact the fetus through causing limb problems. Thereby, the mother can also be RH incompatible and it is for this reason adviced that mothers with a negative blood type should receive RhoGAM to prevent the problem from occuring.(Medical Plus) Last, there is also the risk of amniotic fluid leakage which can develop a condition of low amniotic levels causing the medical problem known as oligohydramnios. If this is not treated and the leakage continues the fetus can be born with undeveloped lungs known as hypoplastic lungs.[16]
6) Sufferers of the Fragile X Syndrome may have symptoms that range from mild to acute. Account for the possible genetic/biological basis of this.
The Fragile X Syndrome or the Martin-Bell Syndrome is more than just one disorder. It is a family of genetic conditions that can change the life of one individual or certain families as a whole. This happens in different ways. The genetic basis of the Fragile X Syndrome is related to a gene called the FMRI gene. [17]
The Fragile X Syndrome is an inhertied condition that leads to mental impairment. It is actually one of the most common reasons cited for mental disorders that can include disabilities in learning as well as more severe cognitive or intellectual disabilities which is at many times also classified as mental retardation or a mental handicap. The Fragile X Syndrome or FXS is also the most commonly known cause of autism or behaviors considered to be autistic. [18]
Generally there are two types of FXS: the severe and less severe form. The genetic or biological basis of this is complicated but is generally explained in gender terms. FXS is also identified as a sex-linked abnormality since it differs in severity and form between the male and female. Males with FXS suffer from the disorder but in a manner that can be either mild or severe and includes at many times some form of an intellectual handicap. Females on the other hand are perceived to be more impacted in a milder way than males.[19]
The genetic basis of the difference in either severity or mildness of the disorder between males and females is based on the gene itself that causes the impairment. FXS is caused by a mutation in the FMR-1 (Fragile X Mental Retardation) gene which is based on the X chromosome that happens to be one of the two chromosomes which determines the sex of an individual. Males have an X and a Y chromosome, while females have two X chromosomes. The mutation of the gene in the X chromosome leads to a development of a new pattern which makes it different from a parent X chromosome gene. Males are more vulnerable to the severe form of the FXS disorder because they simply have only one X chromosome copy. Since women have two a certain balance can be reached between the mutated and the normal gene. This is the genetic explanation for the increased chances among males to develop the severe form of the FXS disorder in comparison with women. [20]
7) Explain the significance of CGG trinucleotides to the Fragile X syndrome. a) Evaluate the importance of biochemical assays in pre-natal diagnosis. b) b)Blood samples (from patients of all ages) can indicate high levels of creatine kinase (ie. above the normal range). What other factors might you take into account to aid your interpretation of these levels?
Trinucleotide repeat disorders are a type of genetic disorders that are caused by the repeats of trinucleotide in certain genes.[21] Trinucleotide or DNA-triplets cause genetic disorders and physical impairments. The Fragile X Syndrome is an example of this condition because of fact that it is caused by the CGG repeats which can range between the 230 to the 4000 in comparison with that of a normal person, a five to a 54. The expanded CGG repeat can bring about the FXS condition in males and females resulting in mental handicap, learning disabilities and distinct facial differences. In short, the FXA is caused by the mutation of the FMR1 gene which can be found on the X-chromosome. The relationship of the CGG trinucleotides to the Fragile X syndrome is through the Codon which is thus the CGG. [22]
The Fragile X syndrome is thus related to the number of trinucleotide CGG repeats at the level of the FMRI gene which is located on the X chromosome. Prenatal testing, and specifically the biochemical assays enables the proper diagnosis of the disorder. The baby is tested before its birth for fragile X mutation which is why the procedure is referred to as pre-natal. The biochemical assays process is performed on the unborn baby using one of two methods: either chorionic villus sampling (CVS), performed at approximately 10 weeks of pregnancy: or amniocentesis, which is done at around 16 to 20 weeks within the pregnancy. (Finucane) The fetus’ surrounding environment is closely observed through advanced technology. The importance of this process is simply in enabling early detection of the development of the disorder in the fetus since there is always a fifty percent chance that the mutated chromosome of the mother will pass the disorder to the child. Considering the seriousness of the impairments the FXS can cause, it is hence significant to detect it and treat it before it becoming a source of handicap for the unborn child. [23]
Creatine kinase is also known as creatine phosphokinase (CPK) or phospho-creatine kinase and is an enzyme tthat is simply made out of several tissues and cell types. Creatine’s function is supporting the muscle system of the body and is hence produced naturally and stored in skeletal muscle. Creatine is also responsible for regulating anaerobic metabolism and is generally assessed in cases of impairment or muscular damage. The amount of creatine kinase is evaluated through blood tests who measure the amount of it. Abnormal high level of the substance couold indicate kidney failure or a neuromuscular disorder.[24]
If the process of muscle generation ever occurs in the body then the amount of CK rises in the blood leading blood tests to be the most effective method through which to assess the problem. However other factors could also impact the patient’s condition and ought to be taken into consideration.
Age, diet, stress, altitude, dehydration, drug, therapy, smoking, gender and pregnancy are all factors that could determine the levels of CK found in the blood after a test. Those conditions are known to cause changes in the system. For instance, pregnancy results in certain physiologic changes in the systems of the body which means that the tests can be influenced by the body fluids increase resulting from the condition of pregnancy. Those body fluids can simply alter red blood cells leading to lower red blood counts on the test results. This is just one example. Gender on the other hand plays a role in the way the blood components are concentrated and can impact the levels of CK read on a certain blood test result. Last, stress is another strong example to provide in this perspective. It has been shown that it is capable of decreasing serum iron and increasing adrenal hormone values in the blood. All those conditions, and several others, could play a role in the way the blood test results are read when the CK levels are analyzed. [25]
What are Barr bodies? Why are they formed? a) Explain the term aneuploidy b) Outline the theoretical and practical procedures of karyotyping, explaining the purpose of the reagents/procedures used. c) For one named aneuploid condition, state the prognosis and treatment of the disorder. Include the role of a genetic counsellor. d) Critically evaluate how effectively the above named condition (in 8.c) can be detected/treated.
A Barr body is an inactive X-chromosome that is generally a feature of female cells and is characterized by the inactivation of one X-chromosome in the cell through a tightly-wound form: the barr body. The barr body is formed as a result of the presence of two X chromosomes in the female of which one is inactive and becomes with time condensed and crumpled leading to the formation of a tighly-wound structure. [26] Though inactivated, the barr body is replicated before the cell division, a process through which a cell parent is divided into daughter cells, and passes in this way on to all the cells of the original embryonic cell with the inactive X-chromosome. The barr body is also recognized by the dark and staining blob it features in the interphase nuclues and is a genetic feature which has been discovered by Murray Barr, after which it is clearly named.[27]
Men are also capable of having a barr body and have an inactive Z chromosome instead of an X chromosome as is the case with females. The process through which those chromosomes become inactive is referred to as lyonization which is simply a hypothesis that revolves around the notion that cells with many X chromosomes are all, except for one, inactivated, a process that happens randomly in most mammalian creatures. This mammalian X-chromosome inactivation is started centrally in the cell through the X inactivation centre or Cix which is found near the centromere.[28] This center is made up of twelve genes and seems to play an essential role in determining that X-chromosome inactivation only happens when two are prsent in a cell.
Aneuploidy is defined as a chromosome abnormality which means therefore that it is a cause of several typs of genetic disorders noticeable at birth on a physical or mental level. An extra or missing chromosome is what is termed a chromosome abnormality and is also noticeable in cancer cells. [29]Aneuploidy occurs during the process of cell division when the cells do not separate properly leading thus to the misproportionate ditribution of chromosomes across the cells. Aneuploidy differs logically enough in each specie considering the fact that the distribution of chromosomes is also different across each type of creature. Yet, what all have in common is the fact that Aneuploidy is a genetic abnormality that is a cause of many disorders. [30]
Considering the human body, it is known that each cell contains 23 pairs of chromosomes which thus means that there is a total of 46. Each pair contains a chromosome inherited from the father and one from the mother. The first 22 of chromsomes are arranged in a karyotype while the 23rd are the sex chromosomes.
A karyotype is a procedure during which the 22 first pairs of chromosomes in a cell are arranged from the largest to the smallest. A karyotype is thus comparable to a photograph of a cell and the theoretical and practical procedure through which this is achieved depends on certain factors.
A karyotype is usually conducted with blood cells, fetal skin cells, either extracted from the amniotic fluid or the placenta, and sometimes even bone marrow cells. Not all types of cells are thus suitable for the karotype procedure. The purpose of karotyping is providing information about certain medical conditions such as the down syndrome that can be observed through the presence of an extra chromosome number 21. The analysis of the “photograph” and the presence of any defects in the pattern sheds light on the patient’s condition and helps doctors diagnose certain medical conditions. The practical procedure through which this is done is however more complex and requires therefore up to one week.
The sample is of course first collected from the patient and is then transported to a laboratory where the cells are separated in order for the scientists to be able to analyze the chromosomes. In blood, the white cells are actively engaged in dividing cells. The non-dividing cells are separated from the diviiding cells and are then grown in special facilities to enable the researchers to have access to the proper and right amount of cells to be analyzed. This process could take a few days. Chromosomes are then condensed which is done through a specific stage referred to as the metaphase. Cells have to be again treated with chemicals to enable them to become compact. Aftr this, the chromosomes are pushed out of their white blood cells. This is again brought into effect through the treatment of the white blood cells with a special chemical solution that causes them to open up.The chromosomes are then strained and analyzd which is brought into effect through counting the chromosomes, sorting them and finally looking at the final stucture. The karotype test is thus very time consuming yet what remains obvious through the depiction of the theoretical process so far is the complexity of the practical one due to all the meticulousness and patience it takes to treat the cells with several substances over a specific and calculated period of time to enable the results to be as accurate as possible.[31]
Each part of the proocedure developed in the aforementioned, serves a specific purpose. The separation of the cells is important as the whole karotyping is dependent on the inclusion of actively dividing cells. Growing cells is significant as it allows the scientists to have enough access to actively dividing cells during the complete test period. The synchronization of the cells is important since, as mentioned , cells can only be seen if they are compact and can only be oberved more closely of they are released from their white blood cells. The staining of the cells is logical since chromosomes are naturally colorless and to be able to distinguish one from the other a special Giemsa dye has to be applied which leads to the final stage of the procedure: analysis. The final step is of course important as it simply is the final sum up through which the findings can be reached.
As mentioned before, the aneuploid condition is characterized by chromosome mutations where the number of chromosomes is noticeably abnormal within a cell. The prognosis of this genetical disorder is mainly connected to the Down Syndrome which is caused by an extra copy of chromosome 21 that is also known as trisomy 21 and leads to mental retardation and several other problems and impairments noticeable at birth. Those could also include heart problems. Thereby, the aneuploid condition is predicted to increase the chances of the Turner syndrome which is the direct result of the absence of one of the sex chromosomes. Impacted individuals suffer from heart problems and kidney problems. In addition to this, scientists who observe , through the procedure of karyotyping, an extra copy of chromosome 18, know the fetus to have a high risk of being born with severe forms of mental retardation combined with a high chance of death durin their first few months. The same is also concluded in regard to the presence of a double copy of chromosome 13. As for the observation of chromosomes 8, 9, 15, 16, 17, and 22, a high risk of miscarriage is generally more present. Through detecting these aspects and facts about chromosomes dictors can generally make a fairly accurate prognosis enabling them to treat the paient and the unborn child more effectively.[32]
Treatment of the aneuploidy condition varies from the severe decisions that involve termination of pregnancy, in case a serious and crippling birth defect is detected, to other treatments which could alo include a genetic counsellor. In the case of cancer patients, ,where aneuploidy plays also a determining role as has been examined before, in the illness’ development through impacting the cell physiology and manner of prolifration, treatment of pathways that aneuploid cells require, through the enhancement of compounds, could prove to be a very effective method through which to deal with several types of cancers. [33]
Genetic counselling is also included in treatment programs of aneuploidy. Many couples are referred to genetic counselling after the detection of abnormalities in the fetus’ development or because of a general family history of genetical problems. A genetic counsellor’s work involves reading the case, the couple’s family background and medical history, and evaluating through this whether or not more tests should be conducted which would from there determine the decision of the counsellor to either advise for more tests, provide the rest of the family, if it is a case of an in-at risk family, with a summary and proceed also to decide about the proper treatment and decision to be taken . Those could include medication, psychological therapy to emotionally prepare the parents to deal with the either mentally or physically impacted child, termination of pregnancy in case the birth defect is predicted to be too severe, and after-birth treatment of the child itself. The choice and course of counselling depends all on the severity of the case based on the results from the tests. [34]
9) Evaluate the effectiveness of gene therapy in the treatment of cystic fibrosis. Include a comparison with traditional methods of easing/alleviating the symptoms of this condition.
Cystic fibrosis is a common inherited disease that is characterized by thick mucus accumulation in the lungs which could impact the whole body. The impacts range between progressive disabilities or even death. Cystic fibrosis is treated through several methods that include the traditional cures as well as the more recent approach of gene therapy. The effectiveness of the latter remains to be estimated through an assessment of its success especially in regard to the other treatments. [35]
Gene thrapy is said to have the potential to cure aptients with cystic fibrosis and is conducted through the insertion of genes into the patient’s cells and tissues. The mutated and defected gene is replaced by a healthy oneCystic fibrosis is an abnormal conditon caused by the gene CFTR . Scientists have been inserting the gene with a lipid and providing the patients with it in the form of an aerson to the lungs and to the nose. The treatment’s effectiveness has been assessed several time through for instance the administration of placebos to the patients. This was for example done in a research conducted in London. The results of this study concluded that the provision of the gene to the lungs resulted in a 25% “restoration of normal chloride transport in the patients who received the CFTR gene treatment but not in the placebo-treated patients.” This led to the final conclusion that gene treatment in this disorder’s case does indeed help in treating it with significant results which led the panel of researchers to sum up their rport with the following words:” Gene therapy for cystic fibrosis continues to make steady progress towards becoming a realistic therapeutic option for the disease,” [36]
Though gene therapy for cystic fibrosis appars be generally effective and promising in dealing with the disease it is essential to reflect on the other treatment methods of the disease and their role in lessening the negatives for the patients. These can include drug therapy, which is still under continous development. Treatments in general aim at handling chest infections to prevent further damage to the lungs in addition to improving nutrition and incrasing th patient’s healthy diet through adding supplements containing enzymes in order to help with digestion.
Chest therapy comprises drainage of the mucus from the lung while the back is vibrated to eliminate the mucus from the airways. Excercise could also help in achieving this and improve the patient’s condition. Medications could help with couging, breathing and other lung problems. Compared to gene therapy, these more traditional methods are also effective and help in improving the standard of life of the patient yet the results of gene therapy are promising grand results that could make a significant change in the illness’ presence within the system of the patient decraeasing it by large percentages. However, medication, drugs and chest therapy are also in constant development and asssessment and will continue to play a role too in the medical field when it comes to dealing with cystic fibrosis. [37] To some people, it makes sense that this genetic disorder ought to be treated genetically while others will prefer other mehods. In conclusion, gene therapy is a promising way of tackling this particular disorder.
10) Explain how and why chromosomes are grouped when compiling a karyogram.
Chromosomes ar grouped during the compliation of a karyogram for the reason that the process itself aims at pairing and ordering all the chromosomes to provide a clear insight into an individual’s chromosomes. This is simply done to maximize the information’s validity that is obtained through the chromosome preparation. The standard format is internationally defined by rules. All the non-sex chromosomes are numbered from 1 to 22 while the sex chromosomes are numbered 23 and they are all arranged from large to small except for chromosomes 21 and 22. The specific arrangement of chromosomes in a diagram in the manner described and in groups enables the clear and quick identification of abnormalities. It is especially noteworthy to note that ” the banding patterns between the two chromosome copies, or homologues, of any autosome are nearly identical.” [38]Differences will be therefore easily identified. Subtle variations between the homologues can be explained in terms of “natural tructural variability”[39], but other more serious cases cannot be so simply dismissed which is why the grouping and ordering of the karyogram, in the internationally defined method, is so important.
11) Outline the variety of roles involved in the work of a genetic counsellor.
A genetic counseller’s work is characterized by variety of roles as well as diversity and deepness of knowledge. A genetic counsellor ought to know for instance how to deal with the psychological aspects of handling cases of genetically predicted birth defects. His tasks and roles could include also any of the following:
Non-direcive provision of information about inheritance of illnesses and their risks.
Addresing the questions and concerns of the patients, families and health care providers.
Providing psychological and emotional support to the families dealing with the illnesses.
Identification of families at risk.
Analysis of information provided about the disorder in addition to analysis of inheritance patterns.
Estimation of recurrence possibilities especially in families at risk.
Advicing the patients about testing options. [40]
12) Outline the technique of karyotyping, including an explanation of the use of Colcemid solution and KCI, and briefly note the application of this technique.
The procedure of Karyotyping has already been referred to and can be briefly oulined as generally requiring the following steps of execution:
Removal of blood from the patient
The white blood cells are removed from the blood or the living cells are separated from the fluid.
The cells are then cultured and undergo mitosis.
Mitosis is halted at metaphase with the aid of chemicals.
The cells are spread out on a slide.
The cells are viewed under a microscope
The chromosomes are pictured. [41]
The usage of the Colcemid solution and KCI is also part of the procedure. Colcemid enables for the halting of the cells in metaphase which enables karyotyping to be performed as the cell harvest can then begin. KCI is included to color the chromosomes and be able o separate and distinguish them considering their colorless nature that would otherwise complicate that. These teechniques aid in the suceesful fulfllment of the karyotyping procedure.
13) Evaluate the accuracy of two named current tests used in prenatal diagnosis of genetic disorders.
There are variou types of prenatal tests that attemp to determine th presence of genetical disorders in a child before its birth. The amniocentesis and the CVS ( chorionic villus sampling) are the most commonly used and known tests for this purpose and are generally fairly accurate.
Amniocentesis is a procdure during which a small sample of the amniotic fluid, which surrounds the fetus, is extracted and used to detect disorders in chromosomes. The risks of this test are fairly small in comparison with CVS which has a higher rate of miscarriage. The amniocentesis involves inserting a needle through the woman’s abdomen to extract the fluid which is thus after that transferred to lab for analysis. The question about effectivenes in determining genetical disorders between week 15 and 20 of the birth is generally positive. Amniocentesis is based on the analysis of the sample’s chromosomes which is a technique that has proven to be very successful and highly acurate in the genetical disorders field. This means also that CVS is as accurate as amniocentesis considering its adoption of the same technique. What differentiates the two tests are details in the way each procedure is carried out. This impacts at certain times the accuracy of the results obtained in the case of CVS. Thereby, some women may simply not obtain accurate results during the first testing because of their genetic and physical conditions that either enable them to be candidates for CVS or not. Factors that could also impact the accuracy of the test is whether the physician obtained a sample that had enough tissue to grow in the laboratory. Last, if the side effects of the test, such as vaginal infection, occur then the results remain inconclusive, inadequate and thus incomplete. These problems with CVS testing influence the type of results only with certain cases and women. The risks of this are higher wih CVS in comparison with amniocentesis but this does not mean that, once the procedure is carried out well and does not include any side effects, that the results can’t be as accurate as with the amniocentesis test .[42]
14) Discuss a selection of ethical issues that may be raised when a prenatal genetic disorder is detected.
Prenatal testing enables early detection of any genetic disorders. The impacts of this on the parents, their decisions and the treatment adopted is however an ethically torn subject considering the complexity of the issue and the impossibility to avoid drastic change in the life of one or all the idividuals involved. For instance, cases that include severe predicted defects are at many times terminated leaving the question about ethicality of choice hang in the air. However, though essentially hard and decisive as a decision, a choice alike is clearly not cruel but ethically correct considering the fact that a child in that position would only be born to uffer extremely and at many times die early. Terminating the pregnancy would be the humanistic, rather than ethically incorrect, thing to do.
On the other hand there are the treatments, such as gene thrapy, that remain ethically very contested as subjects. Several issues simply raise as sources of problems. Respect for individuals’ rights of self-determination came into conflict with the scientific and medical field’s prviously uncontested and undoubted care of the patient in the best manner possible.The field of bioethics does illustrate this further. There have been for instance cases where patients claimed to not have been fully informed about genetical therapy or other treatments. Ethical concerns could be dealt with effectively through anticipaing them beforehand and poviding professional advice and counselling to patients afer that.[43]
15) What effects may Lyonization have on the expression of X-linked disorders in males and females. Include structural and functional implications
Lyonization or X-inactivation has certain impacts on the expression of X-linked disorders in males and females. X-linked disorders are many and have been assessed to be around 200 in both males and females. Those impairments could include fragile-X-linked mental retardation, X-linked ichythyosis and X-linked agammaglobulinaemia. However, though both mals and females are affected by lyonization, only males are impacted by the recessive inheritance feature of the disorder. Both males and females show however a pattern in the expression of the X-linked disorders as both genders have no variation in expression since the disorder will always follow a predictable pattern of evolvement. Females do rarely display signs of X–linked diseases because of what is known as atypical lyonization or a new mutation in the second X chromosome. This means that women generally evolve a milder form and signs of the X-linked disorders. [44]
In X-linked skin disorders, Lyonization tends to bring about a mosaic pattern and is observed through the emergence of the Blaschko lines. [45]Lyonization has structural and functional implications as an observable process which, as mentioned, follows a certain typical course with both males and females. For instance , an affected male will generally have no affected sons or daughters but his daughters will be carriers with a future fifty percent chances of transmitting the disease to their children. Sons of the impacted male do not inherit the gene since male-to-male transmission is not possible. In general, the x-inactivation is a predictable procedure which means that the structural and practical aspects of the process for the male and female might follow a different course but are classified as very typical.
[1] ‘Isoelectric Point’ http://en.wikipedia.org/wiki/Isoelectric_point accessed 4 January 2010
[2] S Lubert, “Biochemie” (Spektrum Akademischer Verlag: 1996) 50
[3] K Shimura ‘and others’, “Accuracy in the determination of isoelectric points of some proteins and a peptide by capillary isoelectric focusing: utility of synthetic peptides as isoelectric point markers.” http://www.ncbi.nlm.nih.gov/pubmed/11028642 accessed 5 Jan 2010
[4] ‘Medhelp’, ‘Phenylketonuria’ http://www.medhelp.org/lib/pku.htm accessed 4 Jan 2010
[5] ‘Wikibooks”Handbook of Genetic Counseling/Phenylketonuria (PKU)’ http://en.wikibooks.org/wiki/Handbook_of_Genetic_Counseling/Phenylketonuria_%28PKU%29 accesed 4 Jan 2010
[6] ‘Wikibooks”Handbook of Genetic Counseling/Phenylketonuria (PKU)’ http://en.wikibooks.org/wiki/Handbook_of_Genetic_Counseling/Phenylketonuria_%28PKU%29 accesed 4 Jan 2010
[7] ‘Wikibooks”Handbook of Genetic Counseling/Phenylketonuria (PKU)’ http://en.wikibooks.org/wiki/Handbook_of_Genetic_Counseling/Phenylketonuria_%28PKU%29 accesed 4 Jan 2010
[8] ‘Medhelp’, ‘Phenylketonuria’ http://www.medhelp.org/lib/pku.htm accessed 4 Jan 2010
[9] S Dawson and others, ‘Galactosemia: A Genetic Study of Four Generations by Enzyme Assay’ http://archpedi.ama-assn.org/cgi/reprint/100/1/69 accessed 4 Jan 2010
[10] ‘Galactosemia’ http://en.wikipedia.org/wiki/Galactosemia accessed 4 Jan 2010
[11] S Dawson and others, ‘Galactosemia: A Genetic Study of Four Generations by Enzyme Assay’ http://archpedi.ama-assn.org/cgi/reprint/100/1/69 accessed 4 Jan 2010
[12] ‘Galactosemia’ http://en.wikipedia.org/wiki/Galactosemia accessed 4 Jan 2010
[13] ‘MedlinePlus’ ‘Chorionic villus sampling’ http://www.nlm.nih.gov/medlineplus/ency/article/003406.htm accessed 5 Jan 2010
[14] ‘Chorionic villus sampling’ http://en.wikipedia.org/wiki/Chorionic_villus_sampling accessed 5 Jan 2010
[15] ‘MedlinePlus’ ‘Chorionic villus sampling’ http://www.nlm.nih.gov/medlineplus/ency/article/003406.htm accessed 5 Jan 2010
[16] ‘Chorionic villus sampling’ http://en.wikipedia.org/wiki/Chorionic_villus_sampling accessed 5 Jan 2010
[17] ‘The National Fragile X Foundation’ ‘What is Fragile X?’ http://www.fragilex.org/html/what.htm accessed 5 Jan 2010
[18] ‘The National Fragile X Foundation’ ‘What is Fragile X?’ http://www.fragilex.org/html/what.htm accessed 5 Jan 2010
[19] S Edelson,’ Fragile X Syndrome’ http://www.autism.com/autism/behavior/fragilex.htm accessed 5 Jan 2010
[20] S Edelson,’ Fragile X Syndrome’ http://www.autism.com/autism/behavior/fragilex.htm accessed 5 Jan 2010
[21] ‘Trinucleotide repeat disorder’ http://en.wikipedia.org/wiki/Trinucleotide_repeat_disorder accessed 5 Jan 2010
[22] ‘Trinucleotide repeat disorder’ http://en.wikipedia.org/wiki/Trinucleotide_repeat_disorder accessed 5 Jan 2010
[23] ‘Trinucleotide repeat disorder’ http://en.wikipedia.org/wiki/Trinucleotide_repeat_disorder accessed 5 Jan 2010
[24] ‘MDA Publications”Simply Stated . . .
The Creatine Kinase Test’ http://www.mda.org/publications/quest/q71ss-cktest.html accessed Jan 5 2010
[25] DA Cawford ‘ Important Factors That Influence Results of Blood Tests’ http://ezinearticles.com/?Important-Factors-That-Influence-Results-of-Blood-Tests&id=3322865 accessed 5 Jan 2010
[26] ‘MedicineNet”Definition of Barr body’ http://www.medterms.com/script/main/art.asp?articlekey=2434 accessed 5 Jan 2010
[27] ‘Barr body’ http://en.mimi.hu/biology/barr_body.html accessed 5 Jan 2010
[28] CA Rougeulle ‘Controlling X-inactivation in mammals: what does the centre hold?.’ j.semcdb 14, 331-340. (Abstract)
[29] Sen S “Aneuploidy and cancer”. Current Opinion in Oncology 12 (1): 82-8. doi:10.1097/00001622-200001000-0001
[30] ‘Reproductive Genetics Institute’ ‘Aneuploidy’ http://www.reproductivegenetics.com/aneuploidy.html accessed 5 Jan 2010
[31] C O’Connor and others ‘Karyotyping for Chromosomal Abnormalities’ http://www.nature.com/scitable/topicpage/Karyotyping-for-Chromosomal-Abnormalities-298 accessed 6 Jan 2010
[32] ‘Reproductive Genetics Institute’ ‘Aneuploidy’ http://www.reproductivegenetics.com/aneuploidy.html accessed 5 Jan 2010
[33] J Cohen ‘Complete Information on Aneuploidy With Treatment and Prevention’ http://www.streetdirectory.com/travel_guide/112989/medical_conditions/complete_information_on_aneuploidy_with_treatment_and_prevention.html accessd 5 Jan 2010
[34] ‘Pregnant Women’http://www.bcchildrens.ca/Services/MedicalGenetics/PregnantWomen.htm accessed 6 Jan 2010
[35] ‘Cystic Fibrosis Treatments’http://www.cystic-fibrosis-symptom.com/treatments.htm accessed 6 Jan 2010
[36] ‘Doctor’s Guide’ ‘ene Therapy Can Help Improve Cystic Fibrosis’ http://www.pslgroup.com/dg/EE7FA.htm accessed 5 Jan 2010
[37] ‘Cystic Fibrosis Treatments’ http://www.cystic-fibrosis-symptom.com/treatments.htm accessed 6 Jan 2010
[38] C O’Connor and others ‘Karyotyping for Chromosomal Abnormalities’ http://www.nature.com/scitable/topicpage/Karyotyping-for-Chromosomal-Abnormalities-298 accessed 6 Jan 2010
[39] C O’Connor and others ‘Karyotyping for Chromosomal Abnormalities’ http://www.nature.com/scitable/topicpage/Karyotyping-for-Chromosomal-Abnormalities-298 accessed 6 Jan 2010
[40] ‘World Health Organization’ ‘Genetic counselling services’ http://www.who.int/genomics/professionals/counselling/en/ accessed 6 Jan 2010
[41] ‘Karyotyping Procedure’ http://home.earthlink.net/~heinabilene/karyotypes/procedure.htm accessed 6 Jan 2010
[42] ‘Lucile Packard Children’s Hospital at Stanford’ Common Tests During Pregnancy’ http://www.lpch.org/diseasehealthinfo/healthlibrary/pregnant/tests.html accessed 6 Jan 2010
[43] L Parker E Gettig ‘ Ethical Issues in Genetic Screening and Testing, Gene Therapy, and Scientific Conduct’ http://www.acnp.org/G4/GN401000180/CH176.html accessed 8 Jan 2010
[44] ‘X-linked recessive disorders’http://www.gpnotebook.co.uk/simplepage.cfm?ID=-1341784030 accessed 8 Jan 2010
[45] R Happle ‘X-chromosome inactivation: role in skin disease expression.’ http://www.ncbi.nlm.nih.gov/pubmed/16720460?dopt=Abstract accessed 8 Jan 2010