Structural elements of a functional eukaryotic chromosome and their functions
The basic structural elements of a functional eukaryotic chromosome are centromere, telomere, and a replication origin. They serve different functions. The centromere joins two chromatids together using cohesins before mitosis is initiated (Nussbaum, McInnes, & Willard, 2007). It also binds microtubules to the mitotic spindle during division. Telomeres are protective caps at the extremities of a chromosome that comprise tandem sequence repeats (Tzanetakou, Nzietchueng, Perrea, & Benetos, 2014). They safeguard sticky chromosomal ends from deterioration or binding to other chromatids. A replication origin is a specific site in a chromosome where the copying of DNA starts.
Telomeres are linked to the lifespan potential in eukaryotes. Their length at birth and in adulthood shows significant variability. Telomeric loss is inversely correlated with late-onset disorders (Tzanetakou et al., 2014). Ongoing research in premature aging focuses on heightened oxidative stress and degradation of telomeres as potential triggers of these diseases (Tzanetakou et al., 2014). The aim is to reverse telomere loss to increase longevity.
The difference among replication, transcription, and translation for both DNA and RNA
According to the central dogma model, replication is the synthesis of two daughter DNA or RNA molecules using a parental unzipped DNA strand or RNA primer as a template (Nussbaum et al., 2007). This semi-conservative process is catalyzed by DNA polymerase and occurs in the 5’ to 3’ direction. In DNA replication, complementary nucleotide bases are paired together (Adenine with Thiamine and Guanine with Cytosine) to form a double-stranded molecule (Seibert, 2014). Thiamine is replaced by Uracil in RNA copying.
Transcription is the biosynthesis of RNA from a DNA template in a process catalyzed by RNA polymerase (Nussbaum et al., 2007). The product (transcript) is usually a single-stranded molecule (mRNA). In contrast, translation entails protein synthesis from an RNA template. A transfer RNA reads the transcript copied from DNA and joins an amino acid to a primer based on a three-nucleotide sequence (codon) to form a peptide chain (Nussbaum et al., 2007). The proteins produced serve different functions in the cell.
Factors associated with a complex inheritance health issue
Disorders with complex inheritance are often multifactorial. A number of factors are associated with their causation. First, multiple genes are involved, resulting in different disease severity and susceptibility to complex disorders (Nussbaum et al., 2007). The allelic heterogeneity means that their inheritance does not follow the Mendelian model. Second, environmental factors interact with genes to cause autosomal disorders with complex genetics. According to Nussbaum et al. (2007), relatives sharing disease-predisposing alleles may all not suffer from the same condition due to gene-environment interaction effects. Thus, these individuals may not exhibit the Mendelian pattern of inheritance for the disease.
Third, familial aggregation is frequent in disease associated with complex genetics. In this case, the probability that a close relative will suffer from a disorder affecting a family member is higher than that of an unrelated person (Seibert, 2014). Heritable disease-predisposing alleles increase the risk of disease in related individuals. Fourth, genetic concordance for a complex disorder is more common in identical twins than in fraternal ones (Nussbaum et al., 2007). The reason for this scenario is that shared alleles in monozygotic twins predispose them to disease.
Genomic tests for screening, diagnosis, and management of a disease
Different types of genomic tests exist for screening, diagnosis, and management of diseases. One of such methods is single-gene testing where a gene of interest is compared to a reference sequence to identify disease-predisposing single-nucleotide variants (SNVs) or copy number variants (CNVs) (National Academies of Sciences, Engineering, and Medicine [NASEM], 2017). It is used in the diagnosis of disorders where phenotypic traits (symptoms) are associated with particular polymorphisms.
In contrast, whole-exome sequencing (WES) is used to screen for variants localized in exomes. The aim is to identify SNVs or CNVs implicated in Mendelian diseases. WES utilizes “capture kits that are based on hybridization methods” to separate the exome from the genome (NASEM, 2017, p. 22). Unlike single-gene tests, WES uses the NGS method only to obtain the sequence, which is then screened for variants associated with a specific pathology. Current estimates show that the sensitivity of the hybridization step in the WES method is 85-90%; thus, this test has a significant clinical utility if the targeted sequence is small (Nussbaum et al., 2007). Outcome data for single-gene tests is unavailable.
Models for multigenerational family health histories
Two models can be used to assess family health history: pedigree chart and family tree (Stefansdottir, Johannson, Skirton, & Jonsson, 2016). These methods can help identify the risk of heritable disorders with a genetic basis for patient counseling. In a pedigree chart, an individual’s direct ancestors are identified, which makes it less comprehensive or informative than a family tree that lists all relatives (Seibert, 2014). The two models are useful for risk assessment to inform disease diagnosis and management.
I would prefer a pedigree chart because it gives a snapshot of family-related risk factors and it is a more cost-effective tool to complete than a family tree. It also shows patterns of direct inheritance of predisposing alleles, and thus, it can be used in genetic counseling. Clinicians can also use a pedigree chart as a visual tool to demonstrate the age of disease onset based on family dynamics.
The importance of a comprehensive health and physical assessment
The rationale for gathering patient data is to evaluate risk. A comprehensive health and physical exam give insights into a person’s health condition and helps identify at-risk individuals. By considering genomic and environmental influences, a nurse practitioner (ARNP) can estimate “risks for Mendelian and multifactorial disorders” for personalized care – screening and genetic counseling (Seibert, 2014, p. 20). In particular, a family health history (FHH) can reveal genetic red flags, such as ethnic predisposition, early disease onset, and family members with related disorders.
A pedigree chart spanning three generations can give adequate FHH information for an ARPN to estimate the risk of genetic disorders (Stefansdottir et al., 2016). An electronic version of this tool can ease data retrieval and updates. Inbuilt electronic health records of relatives can give information about family dynamics – genetics, diet, and physical activity – for optimal care.
Genetic test and its impact on health, prevention, screening, diagnostics, treatment selection and effectiveness
Cancer initiation is linked to sporadic mutations in the oncogenes that cause uncontrolled cell proliferation (Nussbaum et al., 2007). Genetic testing for these tumors screens for predisposing mutant BRCA1 and BRCA2 genes. Although the test is critical for managing breast cancer, insurers may use the genetic information to deny patients life insurance because of increased disease risk that reduces age-specific survival rates.
One genetic test for cancer is gene expression profiling to characterize tumors. This approach has been used in the screening and diagnosis of Burkitt lymphoma based on expressed surface proteins (Nussbaum et al., 2007). If the expression levels are significant, therapy can be recommended to prevent tumor development. The test helps distinguish this cancer from a more severe subtype, B-cell lymphoma, which requires aggressive interventions (chemotherapy) (Seibert, 2014).
Pharmacological agent with a protocol/clinical guideline that may not take into consideration genetic variations
Genetic risk information has been utilized to tailor treatments according to genetically determined individual responses to medication to avoid toxicity and optimize drug efficacy. One such pharmacological agent is isoniazid that is used for latent tuberculosis treatment (Nussbaum et al., 2007). The protocol for isoniazid entails a 3-month regimen that is administered once weekly (Amlabu et al., 2014). However, polymorphisms in the N-acetyltransferase gene have created two phenotypes: slow and rapid users.
Patients who inactivate isoniazid slowly are at a higher risk of developing neuropathy than those who metabolize it rapidly (Nussbaum et al., 2007). On the other hand, fast acetylators may not maintain adequate drug levels throughout the week. Thus, the protocol for isoniazid therapy may not consider these genetic variations.
How nutrition can impact this health issue positively and negatively
Proper nutrition is critical in the management of diabetes, a metabolic disorder that is diagnosed when fasting plasma glucose (FPG) level is ≥ 7.0 mmol/L (Evert et al., 2013). Specialized nutritional therapy is required for better glycemic control. Evert et al. (2017) further note that “vegetables, fruits, and whole grains” are recommended over sugars as carbohydrate sources for improved health (p. 3822). Additionally, self-monitoring starch intake has a positive impact on glycemic control by lowering caloric consumption. The use of nonnutritive sweeteners (NNSs) also has the same effect.
On the other hand, an intake of sweetened beverages, including fructose- or sucrose-loaded drinks can impact negatively on one’s cardiometabolic profile (Franz, 2016). High fructose consumption increases the risk of weight gain and insulin resistance (Franz, 2016). Therefore, adherence to the recommended nutritional regimen is critical in diabetes control.
The genetic and environmental influences on the malnutrition disorder
Obesity is a prevalent disorder of malnutrition. It is characterized by an elevated body mass index (BMI). Various risk factors are implicated in its causation. The main causes are a high intake of calorie- and fat-rich food and reduced physical activity (World Health Organization [WHO], 2017). These factors are environmental in nature. Syndromic obesity is known to have a genetic basis. Prader-Willi syndrome (PWS) is associated with heritable chromosomal defects that affect the loci involved in food intake regulation (Seibert, 2014).
Obesity poses a significant threat to the public health system. According to recent WHO (2017) estimates, the global prevalence rate of this condition is 13%. The criteria for testing or diagnosing obesity involve a body mass index of ≥ 30 kg/m2 (WHO, 2017). Treatment options include weight-loss strategies (diet and exercise), pharmacotherapy, and bariatric surgery. The prognosis of obesity entails an increasing waistline and health complications, including cardiovascular diseases and diabetes.
How genetic and genomics can play a role in a demand for new health services and how it may impact health care expenditures in the aging population
Genetics and genomics are changing the healthcare landscape. The demand for personalized medicine in disease diagnosis and management following the conclusion of the human genome project is growing due to the realization that most conditions have a genetic basis (Seibert, 2014). Diagnosis will increasingly focus on identifying disease genes. Genetic testing and counseling will improve early detection and prevention of chronic conditions, such as cancers and birth defects.
Genetics and genomics could also increase healthcare expenditures, especially in the aging population. Insurance premiums that are based on age-specific survival are likely to rise if adults test positive for predisposing alleles (Nussbaum et al., 2007). For example, people with BRCA1 mutations that are associated with a high breast cancer risk may be required to pay more for individual health plans.
The method that uses evidence-based data to support a new or innovative way to care for the aging
Optimal care for the aging baby boomer generation requires improved care coordination to meet its complex health needs. One innovative way to support the elderly is remote monitoring combined with community-based facilities (Choi, Blumberg, & Williams, 2015). Community health nurses can visit patients in their homes for specific tests to ensure a timely management of exacerbations.
Evidence-based data shows that this model of care will improve the management of chronic conditions associated with old age (Clarke, Bourn, Skoufalos, Beck, & Castillo, 2017). Routine tests, patient education on diet and exercise, and referral to specialized care are some of the benefits of at-home patient monitoring. Anticipated outcomes include better management of chronic diseases, reduced hospitalizations, and decreased healthcare spending, among others.
How genetic and genomics can play a role in a demand for new health services and how it may impact health care expenditures in the chronic disease population
Genetics and genomics have been integrated into chronic disease screening and prevention. Genetic tests are becoming a public health priority for rare and single-gene disorders to provide optimal preventive therapy and reduce disease risk in relatives (Burton, Jackson, & Abubakar, 2014). Thus, genetics and genomics will lead to cost-effective management of preventable chronic conditions.
Genetics and genomics will ensure cost-effective preventive and personalized treatment of common conditions. Disease prevention via antenatal and population-level screening and microbial sequencing can help reduce the cost burden of chronic illnesses (Nussbaum et al., 2007). For example, genetics and genomics have been used to develop inexpensive and effective drugs for resistant Mycobacterium tuberculosis strains.
The method that uses evidence-based data to support a new or innovative way to care for those with chronic disease
Caring for patients with chronic diseases requires accessible, safe, and quality care to avoid preventable hospitalizations. One innovative approach used with this population is mobile integrated healthcare (MIH) – a 24-hour inter-professional care coordinated from a command center (Clarke et al., 2017). This model uses diverse community resources and healthcare workers – nurses, physicians, and community health workers – to meet the complex needs of patients (Choi et al., 2015). It ensures adequate, physician-led integrated care to manage chronic disease symptoms in community settings.
The anticipated outcomes of the MIH approach include timely, high quality, and safe care to patients with complex needs. The model will also improve healthcare coordination to advance population health and contain medical costs. It will reduce hospitalizations and length of hospital stay that increase healthcare spending.
News story about genetic or genomic technology
Genome editing is an emerging genetic technology that modifies DNA through the introduction of corrective mutations (Rodriguez, 2016). One such method is the CRISPR/Cas9 technique. Genome editing can be applied in treating disorders by reversing the effects of disease-predisposing genes. New allelic variants can be introduced in the genome to treat chronic conditions, including cancers.
Genome editing raises serious ethical, cultural, religious, legal, fiscal, and societal issues. Ethically, the potential for off-target mutations poses a serious safety risk to patients and the environment (Nussbaum et al., 2007). People may also refuse genome editing for cultural and religious reasons. The technology also raises legal issues related to patenting of human genes for therapeutic application (Nussbaum et al., 2007). From a fiscal perspective, intellectual property rights may make the technology expensive due to an emphasis on profits. The societal implication may include its use in improving athletic performance or intellectual capacity.
Issues that undermine the rights of clients in genetic- and genomic-related decision making and action
The key issues that undermine the rights of clients in genomic-related decision-making are the privacy of medical information and barriers to informed consent. Genomic data may be shared with family members who are at risk of a particular condition, overriding a patient’s decision to have them kept confidential (Nussbaum et al., 2007). Obtaining informed consent from patients in need of gene therapy raises ethical issues.
The potential solution for this issue is assessing family/cultural factors that may affect the utilization of genomic services (Rodriguez, 2016). As a patient advocate, I would recommend health education programs targeting at-risk populations to help address the barriers to informed consent. Such measures will that health beliefs are integrated into genomic services.
References
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