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which would you use to screen and diagnose this issue?

which would you use to screen and diagnose this issue?

which would you use to screen and diagnose this issue?
DNP 810 Topic 2 Discussion Question Two

Refer to the complex inheritance health issue identified in DQ 1. Given available genetic tests, which would you use to screen and diagnose this issue? How can the doctoral-prepared nurse apply this information in practice? Explain. Support your rationale with a minimum of two scholarly sources.

Researchers are learning that nearly all conditions and diseases have a genetic component. Some disorders, such as sickle cell disease and cystic fibrosis, are caused by variants (also known as mutations) in single genes. The causes of many other disorders, however, are much more complex. Common health problems such as heart disease, type 2 diabetes, and obesity do not have a single genetic cause—they are influenced by multiple genes (polygenic) in combination with lifestyle and environmental factors, such as exercise, diet, or pollutant exposures. Conditions caused by many contributing factors are called complex or multifactorial disorders.

Although complex disorders often cluster in families, they do not have a clear-cut pattern of inheritance. It may be difficult to identify the role of genetics in these disorders, particularly because families often also share environments and may have similar lifestyles. This makes it difficult to determine a person’s risk of inheriting or passing on these disorders. Complex disorders are also difficult to study and treat because the specific factors that cause most of these disorders have not yet been identified. Researchers continue to look for major contributing genes for many common, complex disorders.

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What Are the Characteristics of a Multifactorial Disease?
A multifactorial disease has a combination of distinctive characteristics that can be differentiated from clear-cut Mendelian or sex-limited conditions. These traits include the following:

The disease can occur in isolation, with affected children born to unaffected parents. Although familial aggregation is also common (i.e., there may be multiple cases in the same family), there is no clear Mendelian pattern of inheritance.
Environmental influences can increase or decrease the risk of the disease.
The disease occurs more frequently in one gender than in the other, but it is not a sex-limited trait. In addition, first-degreeDNP 810 Topic 2 Discussion Question Two
DNP 810 Topic 2 Discussion Question Two

relatives of individuals belonging to the more rarely affected gender have a higher risk of bearing the disease (International Commission on Radiological Protection, 2000).

The concordance rates in monozygotic and dizygotic twins contradict Mendelian proportions. A concordance rate is a measure of the rate at which both twins bear a specific disease (Mossey, 1999; Griffiths et al., 1999).
The disease occurs more frequently in a specific ethnic group (i.e., Caucasians, Africans, Asians, Hispanics, etc.).
Going back to the example of coronary artery disease, we know that there are a number of factors that increase the risk of disease onset, including obesity, type II diabetes, high blood pressure, high levels of low-density lipoprotein cholesterol, and even gum disease (Myers et al., 1990; Watkins & Farrall, 2006; Williams et al., 2008; Wilson et al., 1998). Although coronary artery disease runs in families, it does not show Mendelian inheritance patterns and can occur in isolation (Yusuf et al., 2004). Coronary artery disease also occurs more often in men than women (Zdravkovic et al., 2002), and its risk is higher among African Americans than among Caucasians or Asians (Clark & Emerole, 1995). All of these characteristics are consistent with the classification of coronary artery disease as a multifactorial disorder.

Are Multifactorial Diseases Continuous or Discontinuous?
Recall that traits that fall into discrete categories are referred to as discontinuous, while those that display a gradient of phenotypes are classified as continuous. Interestingly, there are many diseases that result from discontinuous variation that show complex phenotypes resembling continuous variation (Griffiths et al., 1999). Scientists propose that this is because there is a base of continuous variation on which the susceptibility to a disease develops. According to this theory, a disease develops and is expressed only after a certain critical liability threshold is reached. The further the liability threshold is surpassed, the more severe the disease phenotype is (Mossey, 1999). In contrast, an individual who does not reach the liability threshold will never develop the disease. Therefore, an individual either has the disease or does not, and the disease shows discontinuous variation.
An example of how the liability threshold works can be seen in individuals with cleft lip and palate. Cleft lip and palate is a birth defect in which an infant is born with unfused lip and palate tissues. An individual with cleft lip and palate can have unaffected parents who do not seem to have a family history of the disorder. Despite the fact that the child’s parents may not have the disorder, they may have contributed some underactive genes that are required for lip and palate formation. Indeed, there seems to be a genetic component to this defect, because the incidence of cleft lip and palate is higher in families with an affected child (Mossey, 1999). Additionally, some nutritional deficiencies and maternal cigarette smoking are associated with this birth defect, so environmental factors are also involved (Ericson et al., 1979; Wilcox et al., 2007). When an individual is born with cleft lip and palate, the contributing factors for this condition have surpassed the liability threshold. If the threshold is exceeded by a fair amount, the birth defect increases in severity. In these cases, it becomes more likely that other family members are also affected (Mossey, 1999). Cleft lip and palate is thus a multifactorial disorder with discontinuous variation.

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