Combined Unit Genomics

Heterozygote advantage and impacts public health 

Heterozygote advantage is an advantage that an individual has when he or she has mismatched alleles of a gene. If there is a heterozygote advantage, then it will follow that the carriers of the disease shall be more likely to survive compared to those individuals without the disease allele. Since allele plays a critical role in survival, then it rapidly spread to the entire population one of the best examples is related to sickle cell trait. Red blood cells are vital for transporting oxygen from the lungs to other parts of the body. The red blood cells are round, but sickle cells are damaged affecting their shape. Individuals with sickle cell disease having two copies of the sickle-cell allele, their red blood cell are misshapen blocking blood flow resulting in organ damage, and sickle cell individuals are at risk of complications. Those people with one copy of allele are believed to be resistant to malaria disease hence are said to have the heterozygote advantage. Individuals with sickle cell trait have been argued that their red blood cells are highly resistant to malaria infection hence are protected from malaria having an advantage over those without sickle cell trait (Mikail, 2008, p. 46). 

The other example is related to cystic fibrosis where individuals with this condition also have a heterozygote advantage. Cystic Fibrosis affects an individual’s body severally, but carriers of the gene are believed to have an advantage especially when faced with diarrhea-causing diseases. Research has pointed out that, Cystic Fibrosis is one of the recessive genetic diseases that are mostly caused by a mutation in the CFTR gene. The gene transports chloride ions but in a situation where a person carries two mutations in the gene then Cystic Fibrosis which in the process completely alters production of mucus, sweat, and even digestive juice. Pancreatic obstruction will develop, and this might lead to digestion difficulty while on the other hand, thickened pulmonary secretions will result into lung infections that are high life threatening. Carriers of CFTR genetic mutation have been established to possess an added advantage over that individual who does not carry the gene. Additionally, research has shown that individuals with CFTR mutation will not have Cystic Fibrosis and will have about half of the chloride channels as an individual who is a non-carrier limiting the amount of fluid that an individual’s body will lose due to diarrhea when he or she gets infected with a disease such as Typhoid or Cholera (Nelson et al., 2004, p. 4275). Based on the above two examples, it has been established that heterozygote advantage plays a critical role in the public health where it can be adopted to prevent the spread of certain disease much quickly. Individuals with a heterozygote advantage are thus prevented from certain illnesses compared to those individuals without the advantage. 

Unit III 

Genetic and environmental factors interaction in producing obesity 

Obesity is simply defined as a condition where an individual has too many fats in his or her body for a given weight or height and is often measured by body mass index. Obesity has been reported to have various implication both mental and physical health including, low self-esteem, high blood pressure, heart disease and even diabetes. It has been established that various factors contribute to the emergence of obesity. For instance, an average figure for the majority of the studies has pointed out that obesity is 40 percent genetics and 60 percent as a result of the environmental factors. Environmental factors comprise of numerous elements including the type of food, physical activities and sugar level intake. For the majority of people, obesity emerges from multiple genetic and environmental factors where they correlate or interact with each other. It is worth noting that genes tend to operate additively and in the process gene-gene interaction influences body weight. Research has pointed out that the effect of social environment and gene factors operate through a putative behavioral phenotype which tends to significantly promote positive energy (Mikail, 2008, p. 6). There are certain age-specific genetic effects on the BMI, in that certain obesity-promoting genes are activated at a given age throughout one’s lifespan. Studies assert that the numbers of genes that have a statistical association with fat as well as mat and traits that are believed to be obesity related have increased dramatically in the recent years and the number of genes interacting with the social environment has also increased. 

In most people, a particular physiological mechanism that genes influences obesity entails energy intake and the expenditure pathways. According to Battle & Brownell, (1996, p. 755), individual genes have also been called to liability in the process of energy expenditure such as those that have a relationship to the mitochondrial uncoupling proteins and even the adrenergic systems. Other studies have returned tests with respect to the genetic influence on the eating phenotypes that are independent of body fat. A multivariate analysis that was focused on genetic and as well, the environmental influences on meal-specific energy intake and weight status found that the presence of independent genetic and non-shared environment have a greater influence on meal-specific energy intake. Height is a multifactorial trait implying that it is greatly influenced by genes and environmental factors such as nutrition and overall health. 

The most suitable approach proposed to prevent obesity is to reduce food portion size, cut out sugary drinks and increase physical activity. Studies have shown that genetics plays a key part in obesity hence, there are persons who find difficulties in the maintenance of a weight that’s healthy. It is clear that one cannot change his or her genes hence the need to focus on various environmental factors and in the process develop lifestyle changes that are believed to have a positive effect on weight. Therefore, there is the need to focus the research on gene-environmental risk factors to develop an efficient and appropriate strategy that will help prevent and reduce obesity in the society. Today, researchers have focused more on analyzing the genetics of both multifactorial traits and multifactorial disorders, to help elucidate the pathophysiological mechanisms behind obese condition (Mikail, 2008, p. 73) 

Unit IV 

Government-controlled genetic database 

According to Merz, McGee & Sankar, (2004, p. 1201), the government of Iceland had passed a law that provided a room for the creation of a national health database. Initially, the bill had outlined that only medical and family history records would be included in the database. However, later, the government decided to include4 the genetic information which in the process led to increasing opposition. The bill will be strongly be opposed by doctors, concerned citizens and even organization for scientists. The major reason the bill might not be feasible in the US is that it infringes into the accepted medical, scientific and commercial standards; however, the government will ensure that they obtain consent from the population and organization. Later, in the year, 1998, the bill was passed by the Iceland parliament allowing for the development of a centralized database comprising of genealogical, genetics and even individual’s medical information. It is evident that government-controlled genetic database, similar to Iceland’s might be feasible in the US today. First5, US have adequate resources that would ensure that this is successful. Secondly, US often take into consideration ethical issues related to any project, and this would make the project successful and highly feasible. Since the bill is feasible in the US, I would support the creation of such a database at an ethical level. 

According to Merz, McGee & Sankar, (2004, p. 1201), the rationale for the inclusion of genetic data will be specifically to facilitate for an easy identification of genetic traits and various inherited diseases. First and foremost, this type of database has been established to greatly violate the personal privacy whenever an individual might access personal information of another person, and this might be abused. Experts in Iceland reviewed this project’s privacy and concluded the information in the database to be personally identifiable. Secondly, the Citizens do not have the right to opt to remove their genetic data from the database. Further, in Iceland, the project was argued to have presumed the citizen’s consent and further they are not told what they government would do with these data. Therefore, for the same project to work in the US, there is the need to take into consideration certain ethical considerations including; the citizen’s informed consent, the willingness of the Americans to participate and provide their personal information and lastly, they should understand what the government would do with the collected data. 

This would then facilitate designing of drugs to attack these genetic diseases at the source. The concerned department and sector will then combine the genetic information with various genealogical and health records from every American to come up with a comprehensive database. Ethical consideration must, however, be focused into since the process will entail gathering very personal information of people. Scientists have reported that this will enhance the process of searching for genes associated with a disease. The bill must further be taken into a greater consideration because, it has been argued that in other instances, population genetics tend to have negative consequences where they result into theories of racial superiority, social exclusion and even environmental causes of human illness in addition to the eugenic pressures (Mikail, 2008, p. 84). 

Unit V 

Methods utilized for prenatal diagnosis and ethical consideration 

Prenatal diagnosis is often provided during antenatal care are highly vital in the management of pregnancy and at the same time allow women to make an informed decision whether to continue with the pregnancy that is already affected by a developmental abnormality or to remove it (Strauss, 2002, p. 164). Currently, there are four methods of prenatal diagnosis that can be adopted including the first technique is ultrasound which is considered as the safest and noninvasive method. It is suitable ion evaluating the gestational age, growth in addition to potential structural congenital disabilities. Further, it can detect abnormalities with about 90 percent accuracy. The second technique is amniocentesis where a long needle is inserted into the uterus of the mother to obtain an amniotic fluid sample that contains cells that are shed by the fetus (Mikail, 2008, p. 93). These cells can then be used to determine chromosome abnormalities. The method is also safe and accurate in identifying genetic disorders. The third technique is Chorionic Villus Sampling (CVS) and is often performed between 9 and 12 weeks. Using this technique, a catheter is inserted through the cervix into the uterus to obtain a sample of chorionic villus to evaluate for abnormalities and decision to terminate the pregnancy. The last technique is percutaneous umbilical cord sampling (PUBS) where a needle is inserted into the mother’s umbilical cord to obtain fetal blood then evaluated for a potential metabolism or even hematologic abnormalities. 

Two primary traditions ion ethics are believed to be effective in solving the conflict of interest including ethics of consequences also referred to as consequentialism and the ethics of duty. The human dignity principle is one of the primary ethical principles critical in the analysis of prenatal diagnosis given to pregnant woman. The other critical ethical consideration that has to be focused during prenatal diagnosis is human nature perceptions, integrity, informed consent, quality of life and the principles of need (Dan et al., 20112, p. 1230). The principle of human dignity states that human dignity cannot be proved using empirical test and have some fundamental rights that have to be fully respected. The major issue is whether the prenatal diagnosis violates the human dignity principle and ways to preserve human dignity. The other aspect is the autonomy or self-determination where every individual has the right to make a decision about their life based on their understanding of what is good for life. An individual should, therefore, make the decision to accept or reject a prenatal diagnosis and be free to react to the result. The next ethical issue revolves around the informed consent where the mother must act independently and at the same time make independent choices during the prenatal diagnosis. The next aspect of ethics is integrity and focuses on value and dignity. It is argued that the diagnosis cannot be performed on an individual without her consent. The outcome of a detailed ultrasound examination and the prenatal genetic diagnosis has to be fully protected (Mikail, 2008, p. 113). 

Unit VI 

Genetic metabolic disorders in public health and biological basis for metabolic disorders 

According to Fitzpatrick (2001, p. 153), inherited metabolic disorders can simply be defined as the genetic condition resulting from metabolism problems. Individuals with inherited metabolic disorders often are associated with a defective gene which then results in enzyme deficiency. Newborn screening has been established to be critical to the public health. It has been established that the disorder occurs infrequently, but they together occur commonly enough to the extent that they warrant an effective preventive measure. Secondly, the majority of the community physicians have been reported to lack the critical training in diagnosing and management of the metabolic disorder, and this could not even recognize them even in situations where patients present the signs and symptoms. The condition requires treatment within a neonatal period to avoid possibilities of lifelong mental and physical disabilities. According to Fitzpatrick (2001, p. 155), the automatic screening of all newborn children is vital in early detection and treatment of the disorder. Thirdly, newborn screening can help to avoid a potential situation of mistaking a metabolic crisis for one of the simplest infection in a child. Research has shown that children tend to exhibit a higher level of altered mental status, refuse to feed and vomit when something is believed to be physiological awry. All these symptoms in most instances are confused to the metabolic diseases and also sepsis which is also a common life-threatening disease. Metabolic diseases and sepsis demand an extensive evaluation for effective diagnosis and treatment of a child. Lastly, it is clear that majority of the metabolic disorders display autosomal recessive inheritance patterns implying that there is often a negative family history of this illness. In most instances, the majority of the parents do not have a clue that of the warning signs that their child is at risk, therefore, in this case, the newborn screening will help to overcome the disadvantage and the parent can pursue a prenatal diagnosis in subsequent pregnancies (Mikail, 2008, p. 132). 

Focusing on the biology of the metabolic disorders, there is the need to answers some question related to principles of inborn errors of metabolism, causes of metabolic disorders, diseases manifestation, and mechanisms. Metabolic diseases occur because too much or too little of a metabolite significantly accumulates in the biochemical pathway. In the catabolism, the compound is broken down while in the anabolic; a complex compound is in the process formed. According to Fitzpatrick (2001, p. 153), the genetic metabolic disorder involves mutations which significantly alters the enzymes and in the process controls a given step in the metabolic pathways. In the inherited metabolic disorder, there is a single enzyme that is not produced by the body or at the time produced in a form that does not work. Based on the type of the enzyme and its role, its absence will imply that toxic chemical will build up or on the other hand a vital product might not be produced. Individual with an inherited metabolic disorders often inherit two defective gene copies from each parent. The parents are carriers of a bad gene implying that they carry a defective and normal copy. The child then inherits two defective gene copies hence cannot produce enough of the effective enzyme and at the same time develops a genetic metabolic disorder referred to as autosomal recessive inheritance. 

Unit VII 

Genetic basis for Li-Fraumeni Syndrome and clinical steps for management 

Li-Fraumeni Syndrome (LFS) is one of the rare autosomal dominant disorders that is mostly characterized by a germline mutation particularly in the TP53 and during the early onset cancer forms such as breast cancer. According to Knudsen two-hit hypothesis, he concluded that mutation of one allele would lead to somatic inactivation of the second allele where the cell will gradually lose its heterozygosity. On the other hand, research has pointed out those one-hit effects with no LOH accounts for increasing growth advantage and tumorigenicity (Mikail, 2008, p. 161). The National Comprehensive Cancer Network came up with a clear guideline recommendation for the screening of LFS among family members which helps in the early detection of tumors (Srivastava et al., 1989, p. 747). Studies have however shown that majority of the LFS families have not been diagnosed and this is primarily because of the lack of typical histopathological presentations useful in the identification of these families. In addition to this, diagnosis is often complicated because the majority of the LFS associated TP53 mutation are believed to be missense making clinicians very reluctant to make a diagnosis of the LFS family because of the inherent ambiguity of the missense variants classifications. There is the need to come up with a better molecular diagnosis for the LFS family to ensure that they all benefit from the screening. 

When the syndrome is identified in a particular family, there are specific clinical steps that should be taken for its effective management. No clear evidence has shown that those individuals with the Li-Fraumeni syndrome (LFS) and diagnosed with cancer have to be treated differently from the rest of the patients diagnosed with cancers through the modalities of the surgery and even chemotherapy. Genetic testing has been developed for families in whom Li - Fraumeni is suspected. The management comprises of enhanced screening for breast cancer via semiannual clinical breast exams and breast imaging. There is the need to ensure that radiation therapy is used on these family with utmost causation based on the increasing risks associated with radiation-induced second primary tumors in patients with the Li-Fraumeni syndrome. However, the specifics of the therapy are closely related to the cancer type (Srivastava et al., 1989, p. 747). In the event of surgical care, the physicians must discuss risk-reducing, prophylactic mastectomy with Li-Fraumeni syndrome women. This has to be considered on a case-by-case basis, but this will depend on the cancer risk in addition to the reconstructive options that are available. The next procedure is to provide genetic counseling to the families with the Li-Fraumeni syndrome to ensure that there is an appropriate and clear understanding of various potential risks and evaluation of the genetic predisposition markers. It has been established that Li-Fraumeni syndrome patients in other instances can develop a high anxiety level, depression, and even distress. In this case, it is important that the clinicians offer psychological monitoring to the family (Srivastava et al., 1989, p. 749). 

Unit VIII 

The Great Pandemic 

Flue pandemic that was experienced in 1918 was the most deadliest influenza pandemic and the first of the two global pandemics entailed H1N1 influenza virus. Research has shown that it infected about 500 million –people globally and caused the death of about 50 to 100 million making it the deadliest natural disasters throughout the human history. Research on the frozen victims established that the virus kills via cytokine storm. The virus was harbored in birds then mutated to pigs. It was hypothesized that the virus originated from East Asia but Popular writer John Barry argued that it originated from Haskell County, Kansas. The evidence established that the virus circulated in the European armies before the 1918 pandemic. The virus was easily spread when an infected person coughs or sneezes. The massive troop movement during WWI hastened the spread of the pandemic (Mikail, 2008, p. 192). Due to widespread of the virus, it killed people in every part of the world killing 17 million people in India and 13.88 million in India’s British ruled districts. Further, 390,000 were killed in Japan, 1.5 million in Dutch East Indies, in Tahiti about 13 percent of the entire population were killed while 22 percent of the entire populations of Samoa were killed (Johnson & Mueller, 2002, p. 105). 

After the 1918 second wave had stricken, new cases of the pandemic had dropped rapidly as a result of better medication to treat and prevent pneumonia that often developed when one contract the virus. Other theories argued that the 1918 virus had mutated rapidly to a lesser lethal strain. The new genetic analysis found that mutation was significantly unique to the strain. The new studies have recently revealed that mutations occur in three genes including nrdE, fadJ and pcp and are associated with plague virulence. 

References 

Battle, E. K., & Brownell, K. D. (1996). Confronting a rising tide of eating disorders and obesity: treatment vs. prevention and policy. Addictive Behaviors , 21 (6), 755-765. 

Dan, S., Wang, W., Ren, J., Li, Y., Hu, H., Xu, Z., ... & Xie, J. (2012). Clinical application of massively parallel sequencing ‐ based prenatal noninvasive fetal trisomy test for trisomies 21 and 18 in 11 105 pregnancies with mixed risk factors. Prenatal diagnosis , 32 (13), 1225-1232. 

Fitzpatrick, D. (2001). Genetic metabolic disease. In Fetal and Neonatal Pathology (pp. 153- 174). Springer London. 

Johnson, N. P., & Mueller, J. (2002). Updating the accounts: global mortality of the 1918-1920" Spanish" influenza pandemic. Bulletin of the History of Medicine , 76 (1), 105-115. 

Merz, J. F., McGee, G. E., & Sankar, P. (2004). “Iceland Inc.”?: On the ethics of commercial population genomics. Social science & medicine , 58 (6), 1201-1209. 

Mikail, C. N. (2008). Public health genomics: The essentials . San Francisco, CA: Jossey-Bass. 

Nelson, G. W., Martin, M. P., Gladman, D., Wade, J., Trowsdale, J., & Carrington, M. (2004). Cutting edge: heterozygote advantage in autoimmune disease: hierarchy of protection/susceptibility conferred by HLA and killer Ig-like receptor combinations in psoriatic arthritis. The Journal of Immunology , 173 (7), 4273-4276. 

Srivastava, S., Zou, Z. Q., Pirollo, K., Blattner, W., & Chang, E. H. (1989). Germ-line transmission of a mutated p53 gene in a cancer-prone family with Li-Fraumeni syndrome. Nature , 348 (6303), 747-749. 

Strauss, R. P. (2002). Beyond Easy Answers: Prenatal Diagnosis and Counseling During Pregnancy: EDITOR'S NOTE: The following five papers were presented as part of a panel discussion entitled “Beyond Easy Answers: Prenatal Diagnosis and Counseling During Pregnancy” at the 2000 annual meeting of The American Cleft Palate- Craniofacial Association. The series of papers explore how families and doctors respond when a prenatal diagnosis is made, and consider ethical and social issues around counseling, managing information, and .... The Cleft palate-craniofacial journal , 39 (2), 164-168.