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GENEGENO02 Genetics And Genomics

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GENEGENO02 Genetics And Genomics Question: Prepare a critical review on the topic: CNVs in obesity among Caucasians. Answer: Introduction Obesity is defined as an abnormal accumulation of fats that is risky to the overall health of an individual (WHO, 2015). Health specialists measure the Body Mass Index (BMI) to determine whether an individual is obese, overweight or has an average weight. BMI is calculated by dividing the weight of a person by the square of the height. An individual with 30kg/m2 of BMI is obese. Obesity is a risk factor for numerous complications like cancer, cardiovascular diseases, and diabetes (Esser et al., 2014). Copy Number Variation (CNS), especially the Amylase Gene (AMY1) in the saliva either increases or lowers the chances of obesity among the Caucasians. This paper will critically review CNVs in obesity among the Caucasians. Subject Characteristics In the first article, the investigators selected a population of young adults from Portugal to establish the relationship between CNVs and Obesity. The study involved 262 participants. Out of the total number, 107 individuals were males while the remaining 155 participants were females (Pinho, Padez, and Manco, 2018). The mean age of the participants was 21.08. Out of the total number of participants, 22 individuals fall under the obese category. The obese individuals had a BMI of 30kg/m2 or more than that measurement (Di Angelantonio et al., 2016). 64 participants were overweight according to the cut-off points that WHO defined. According to WHO, an overweight individual is one with a BMI ranging from 25kg/m2 to 29.9kg/m2 (Mata, and Jasul 2017). The remaining 176 individuals acted as a control to the experiment. In the second article, the subjects included 207 Canadians with 96 of them being males and the rest females (Voll et al., 2017). The median age of the participants was 26.7 years. The researchers relied on molecular methods to confirm the 22q11.2 deletions. In the third article, the study population comprised of 779 Italian Children (Marcovecchio et al., 2016). Out of the 779 children, 744 accepted to take part in the survey. Therefore, there were 390 girls and 354 boys. The average age of the participants was approximately 8.4 years. The investigators applied molecular methods to determine the content of AMY1 in the participants. In the forth article, group of subject consisted of 435 individuals with obesity (Hasstedt et al., 2015). The participants had a BMI of 35.5kg/m2 and above. The experiment aimed to establish the relationship between obesity and ARFRP1. Technological Platforms Used In the first article, the researchers extracted DNA from the participants, the amplified the genetic materials using Polymerase Chain Reaction (PCR) kits. The investigators started by using TaqMan assays to target the AMY1 gene (Pinho et al., 2018). The RNASE assay, which acts a reference helped in the evaluation of the quantity of AMY1 in the ddPCR system. After obtaining the DNA samples from the participants, the researchers digested them to separate the tandem copies. In the second article, the researchers applied standard molecular ways to confirm the 22q11.2 deletion.  To determine the relationship between low AMY1 and obesity in the third article, the researchers extracted DNA from saliva samples (Marcovecchio et al., 2016). The researchers extracted DNA using QIAmp kit. Furthermore, the investigators used quantitative PCR to amplify the AMY1 copies. The qPCR contained two TaqMan assays. To establish the relationship between obesity and ARFRP1 in the fourth article, the researchers applied dublex TaqMan assay and qPCR (Hasstedt et al., 2015). The researchers used QIAmp Blood kit to extract DNA. The investigators performed Microassay analysis and scanned the slides using a scanner called RocheNimblegenMS200Microarray. Genetic Variants And Their Functional Consequences The first gene variant associated with obesity is AMY1. The amylase gene is located at the salivary glands, and it assists in the digestion of carbohydrates in the mouth. An individual who has a functional metabolism of carbohydrates can maintain a normal weight (Pinho et al., 2018). However, accumulation of sugars due to improper digestion by the amylases leads to the onset of obesity. Therefore, a person with high amounts of AMY1 can maintain an average weight due to proper metabolism. Low levels of AMY1 elevate the BMI of an individual while high AMY1 decreases the BMI (Marcovecchio et al., 2016). The second gene variant associated with obesity is ARFRP1 which is located at chromosome 20q13.3. Recent research has shown that the ARFRP1 controls both chylomicron formation and lipid droplets. Additionally, the CNV assist in glucose digestion. Thus, ARFRP1 facilitates the metabolism of both fats and carbohydrates. An individual with functional and sufficient amounts of ARFRP1 can maintain a normal weight due to effective digestion (Hasstedt et al., 2015). Consequently, insufficient levels of ARFRP1 lead to the onset of obesity due to ineffective digestion. The third gene variant associated with obesity is 22q11.2. The deletion of CNV 22q11.2 (22q11.2DS) leads to the beginning of obesity (Voll et al., 2017). 22q11.2DS not only causes obesity but also leads to the development of Schizophrenia, hypothyroidism, and intellectual disability. Conclusion Obesity is defined as the excessive accumulation of fats that poses a health risk to an individual. A study involving young Caucasians indicated that high levels of AMY1 lead to the maintenance of normal weight.  Additionally, the reduction in AMY1 leads to the onset of obesity. The investigators digested the DNA samples from the participants before amplifying the strands using PCR. The results of the study indicated that low AMY1 elevates BMI. Apart from AMY1, ARFRP1 and 22q11.2 are also associated with obesity. Increased levels of ARFRP1 reduce the chances of obesity. Similarly, 22q11.2DS causes obesity and other complications like hypothyroidism and schizophrenia. References Di Angelantonio, E., Bhupathiraju, S.N., Wormser, D., Gao, P., Kaptoge, S., de Gonzalez, A.B., Cairns, B.J., Huxley, R., Jackson, C.L., Joshy, G. and Lewington, S., 2016. Body-mass index and all-cause mortality: individual-participant-data meta-analysis of 239 prospective studies in four continents. The Lancet, 388(10046), pp.776-786.Retrieved from: Esser, N., Legrand-Poels, S., Piette, J., Scheen, A.J. and Paquot, N., 2014. Inflammation as a link between obesity, metabolic syndrome and type 2 diabetes. Diabetes research and clinical practice, 105(2), pp.141-150. Retrieved from: Hasstedt, Sandra J., Yuanpei Xin, Rong Mao, Tracey Lewis, Ted D. Adams, and Steven C. Hunt. “A copy number variant on chromosome 20q13. Three implicated in thinness and severe obesity.” Journal of obesity 2015 (2015). Retrieved from: Marcovecchio, M.L., Florio, R., Verginelli, F., De Lellis, L., Capelli, C., Verzilli, D., Chiarelli, F., Mohn, A. and Cama, A., 2016. Low AMY1 gene copy number is associated with the increased body mass index in prepubertal boys. PloS one, 11(5), p.e0154961.Retrieved from: Mata, A. and Jasul Jr, G., 2017. Prevalence of Metabolic Syndrome and its Features Across Different (Normal, Overweight, Pre-Obese and Obese) Body Mass Index (BMI) Categories in a Tertiary Hospital in the Philippines. Journal of the ASEAN Federation of Endocrine Societies, 32(2), p.117. Retrieved from: Pinho, S., Padez, C. and Manco, L., 2018. High AMY1 copy number protects against obesity in Portuguese young adults. Annals of human biology, pp.1-5. DOI: 10.1080/03014460.2018.1490452 Voll, S.L., Boot, E., Butcher, N.J., Cooper, S., Heung, T., Chow, E.W., Silversides, C.K. and Bassett, A.S., 2017. Obesity in adults with 22q11. 2 deletion syndrome. Genetics in Medicine, 19(2), p.204. Retrieved from: World Health Organization, 2015. Health Topics: Obesity World Health Organization. Retrieved from:

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