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DNA (Deoxyribonucleic acid) is the basis of life. It is the longest single molecule in the entire human body, the chemical code specifying our function, appearance and lineage and is unique in almost all individuals. DNA is found in chromosomes in the cells of all living organisms; there is very little difference between human DNA and that of any other form of life. All DNA is made up of two strands, comprising a backbone of sugars and phosphates, and four nitrogenous bases (adenine, guanine, thymine and cytosine) twisted around each other in helical shape. The two strands are paired complementarily by hydrogen bonds (A=T, G=C).
 
DNA replication is semi-conservative; during replication the strands separate and identical copies are synthesised using the originals as a template. 

A gene is a length of DNA that codes for a protein. Genes comprise only a small part of the total genome, most of the remainder is non-coding. They are used as the template for the synthesis of proteins -strings of amino acids that have a range of vital functions within the cell. Most genes have two alleles, some more. An allele can be dominant or recessive. It is considered recessive if it will determine the phenotype only when both alleles are identical.

A mutation is a mistake in the code. This can be relatively minor, such as a base substitution, or can involve whole chromosomes, as in aneuploidy. At times even a single-point mutation can have severe effects, depending on where in the code it occurs. Mutations may often lead to irreversible physical or mental disabilities, such as Down's syndrome or sickle cell anaemia.

The MYH7 gene on chromosome 14 codes for the beta-isoform of myosin heavy chain protein, a contractile protein present in the cardiac muscle. Its normal function is related to the proper contraction of the heart. At least 15 mutations have been identified in the MYH7 gene(1), all associated with Hypertrophic Cardiomyopathy (HCM), in which the structure of myosin is altered. The phenotypic effect of the mutated gene is an abnormal thickening of the left ventricular muscle and other irregular muscle structures.

For the majority of affected individuals, this condition will not limit the quality or duration of life. Some, however, experience significant symptoms such as heart murmurs, shortness of breath, chest pain, palpitation, light-headedness and blackouts. There is also a greatly increased risk of heart attacks and sudden cardiac death.

The condition follows an autosomal dominant pattern of inheritance. This means that anyone in the family, regardless of gender, has a 50%(2) chance of developing HCM. People who have parents, siblings or children who exhibit symptoms are more likely to have the mutated allele themselves.
 
The presence of the mutation can be detected by genetic testing. The MYH7 gene of the patient is sequenced and compared to a normal allele of that gene. The DNA is extracted from a sample, usually blood, and purified. Enzymes, such as Taq polymerase, RNA primers and nucleotides are added and the gene is selected for and amplified in a PCR reaction. It is isolated using gel electrophoresis then sequenced in a sequencer by labelling with fluorescent bases.
It can then be compared to an unmutated allele to see where the mutation is.

Coronary Artery Disease (CAD) has similar symptoms to HCM. It is caused by the narrowing or blocking of the arteries due to fatty deposits and can result in chest pain, shortness of breath and a greater chance of serious heart attacks. The risk of developing CAD is increased if the person is 65+, male, a smoker, diabetic, obese, has high cholesterol levels or blood pressure, or has a family history of CAD. More than 80%(3) of all Sudden Cardiac Death (SCD) events are related to CAD.
 
In contrast, HCM frequently causes no or only mild disability over a lifetime, and many patients achieve normal life expectancy (some without even being aware of their disease). Often symptoms do not appear until mid-life, if at all. Only a minority of patients are at risk of SCD, but it occurs most commonly in children and young adults, even if they have been previously asymptomatic(4). Most SCD cases happen when resting, so refraining from vigorous exercise may not prevent it. In both CAD and HCM, the risk of SCD varies with the severity of the ailment, but is greater if the person has had a previous cardiac arrest or has a family history. CAD carries a higher chance of SCD, but is treatable and avoidable. HCM cannot be cured, but often has no adverse effects on quality or length of life.

Grace has the mutation associated with HCM and it seems likely that, while she may not develop symptoms, she is at significant risk of sudden cardiac death. Three of her close relatives have died from SCD, which indicates there is a genetic trend in her family towards that manifestation of the condition. In actual fact she may never develop the phenotypic characteristics; the mutation may simply be a predisposing factor and so its presence alone does not allow an accurate prediction of risk(5). Statistics show that approximately 20%(6) of carriers do not ever develop symptoms and that many achieve a normal life expectancy ¨C the mortality rate of HCM is only 1%(7). In fact, Coronary Artery Disease carries a much greater risk of SCD and has been conclusively linked to diet and lifestyle. The other bus drivers Grace mentions are likely to develop CAD due to their unhealthy lifestyle, and yet they do not risk losing their jobs. It is possible that Grace may never have SCD, and even if she does it may not be while she is driving, which is only for a short period each day. However, if and when SCD occurs it is without warning and if not treated within minutes the chances of survival drop drastically. Most chillingly, there is no effective way of preventing SCD(8).

The main moral conundrum is balancing the safety of the children on the bus with Grace's basic human rights, including the right to privacy. For this an accurate risk assessment needs to be made. For the school board to know about her test results without Grace's consent is a violation of her privacy, but human lives are of utmost importance and if there is any serious danger of harm to the children Grace's rights are only secondary.

Mr. Moral Quandary clearly sees it as his duty to inform the school so that it can ensure the safety of its pupils, which is understandable. But his wife insists that he doesn't know the full implications of the results and that it is not for him to reveal personal information that someone wishes to keep confidential - also easily understandable. She believes Grace should not suffer discrimination due to something which she, literally, cannot change.
 
Mr. Quandary would be breaking client-confidentiality laws in divulging this information, but even so- ethically, it is not his prerogative to make a decision that would have such a detrimental effect on someone else's life. Grace will almost certainly lose her job, which will leave her struggling to support her family, and with few employment prospects. Her insurance costs will rise, if she remains insured at all; she will find it harder to get mortgages and other loans due to prevalent preconceptions about HCM and the significance of her test results. The psychological stress on her and her family will only be added to by this chain of events.

There is also a danger of setting a precedent for similar situations. As Mrs. Quandary says, it is an issue of civil freedom. Whether or not somebody's genetic information should be available to employers and insurance companies is a serious question facing society today. There is a fine line between the right to privacy and the right to security; in some cases an employee is simply unable to do their job to the required degree of safety. But what is an acceptable level of risk? It is hard to define precisely, and even harder when human nature is taken into account. Certainly parents should be equipped with the knowledge to make sensible decisions about the danger they are potentially putting their child in, but in this case it would mean revealing Grace's personal information to the community at large, which really has no business in her private affairs. The onus is on Grace, she is the one making decisions relating to other people's children that could result in their death or injury. Even if she doesn't have an SCD it is also possible that she may experience other symptoms of HCM while driving, such as dizziness or blackouts, with equally disastrous effects.
 
In situations like this, each individual case must be judged on its own merit, and in this case the risk is within acceptable limits. If prejudice on the basis of race, which is essentially a genetic characteristic, is illegal, certainly a person's DNA should not be used against them. Whether or not Grace has done the correct thing in concealing her test results doesn't change the fact that Mr. Quandary does not have the prerogative to reveal them to anyone. The danger to the children is not substantial enough to justify that step.

1. Eur Heart J. 2005 Apr;26(8):794-803. Epub 2005 Mar 15. Mutation screening in dilated cardiomyopathy: prominent role of the beta myosin heavy chain gene
2. http://www.cardiomyopathy.org/html/which_card_hcm.htm, The Cardiomyopathy Association, 29/6/2005
3.http://www.clevelandclinic.org/heartcenter/pub/guide/disease/electric/scd.htm#emergency, Cleveland Clinic Heart Center, 3/7/2005
4. Berul, C., MD, November 2004, eMedicine.com: Cardiomyopathy, Hypertrophic
5. BMJ 1995;310:856-857 (1 April), An Ethical Debate: Genetic testing for familial hypertrophic cardiomyopathy in newborn infants: Clinicians' perspective
6. http://www.hopkinsmedicine.org/cardiomyopathy/sudden_cardiac_death.htm, Montgomery Heart Foundation for Cardiomyopathy, 1/7/ 2005  (Note: Link no longer active - NZORD 11/2008)
7. Maron, Barry J., MD,  Circulation. 2002;106:2419, American Heart Association
8. BMJ 1995;310:856-857 (1 April), An Ethical Debate: Genetic testing for familial hypertrophic cardiomyopathy in newborn infants: Clinicians' perspective