Linkage Disequilibrium: A Case Study

In order to identify a condition as a disease, it should fit certain criteria. One of the reasons that obesity is classified as a disease is because of its large comorbidity. Obesity is a risk factor for chronic diseases such as hypertension, dyslipidaemia, type 2 diabetes, cardiovascular disease, sleep apnoea, musculoskeletal disorders and some cancers (Rossner, 2002). According to Rossner (2002), the death rate from all causes, cardiovascular disease, cancer and other diseases increases among moderate and severe overweight men and women in all age groups. Therefore, obesity is

Some, however, have obesity promoting genes that are much worse, as a disease known as monogenic obesity exists where a single gene produces a high risk of obesity, and it becomes difficult, almost impossible, to reverse (Cimons). This disease is opposite of common obesity, where many genes are involved, and is much harder to treat and study as trying to find only one gene has proven to b difficult. However, there is no question if genes do contribute to being overweight and if this is the case, obesity now becomes much harder to treat and study as finding the exact reason as to why an individual is obese is difficult.

The two recessive alleles are both on the same chromosome. Genes A and B completely follow Mendel’s principles of inheritance; genes B and C are physically connected together and never are separated from each other at any time during any cell division cycle or fertilization event. Draw below the gamete genotypes that this individual could produce.

During the episode, the Special Victims Unit used linkage analysis and geographical profiling. There had been multiple little boys who had been kidnapped all around the same area, so the detectives used linkage analysis to see how and if these crimes are connected. Then, based on geographical profiling, the detectives were able to find the location of the offender. The show did a great job of showing how little information can be used to put bigger pieces together, like the fact that one of the little boys was buried under new cement and the perpetrator, who was an apartment manager, just put in new cement in the building. Having people who can look at those little connections can have a great impact on the process of finding the perpetrator,

has led to public concerns of the obesity issues. Works also have been done lately to identify the obesity associated loci. Speliotes et al. (2010) identified 18 new loci that are associated with body mass index (BMI). Combined with the earlier loci found, there are now 32 significant loci that are associated with BMI. These 32 BMI loci can explain 1.45% of the variance in BMI, which is comparable to a one pound increase in a 160-180 cm tall individual. There are several studies investigating how these SNPs interact with other variables to affect obesity. For example, for those with more risk alleles associated with obesity are more likely than their counterparts to gain weight if they drink sugar-sweetened beverages (Qi et al. 2012). For those who drink sweetened beverages everyday, 10 risk alleles’ increases would lead to 1.78 times increase in BMI. As for sociologists, at first, researchers tried to use the genome-wide gene-by-environment interaction (GWGEI) method to combine GWAS results into the sociological study (Boardman et al. 2014). They used 260,402 SNPs as genetic markers and interacted these markers with educational attainment (as an environment indicator). Several hypotheses on GxE interactions are tested. However, because the data points were too huge, the results were hard to support any of the hypotheses. Also, there could be false positive and rGE issues lurking around the

Obesity represents a condition where individuals put on abnormal, or, above average weights when weighted on the Body Mass Index, BMI, Scale (Thomas, Hyde, Karunaratne, Herbert & Komesaroff, 2008). Acquisition of weight to extreme levels may get attributed to the lifestyle and the genetic affiliation of a given person. In some instances, consumption of junk food and indulgence in

Galston (2013) declares that “social linkage is an inescapable fact” (p.11) because he believes that “the well-being of some people affects the well-being of others” (p.10), this means that the welfare of all human-beings is connected; people will always be affected, whether they like it or not, they have no control over the factors that may have an impact on them.

In this article, the researchers sought to determine if linkage disequilibrium could be used to map disease-causing genes. This is of practical importance to the human population in that, it could lead to earlier diagnosis and prevention or delay of disease progression. The researchers evaluated work of previous studies and expanded it to a larger section genome samples. This allowed the researchers to obtain a greater depth of knowledge in comparison of multiple regional ethnicities. Linkage disequilibrium is the non-random association of alleles at different loci. Disequilibrium occurs when the frequency of a certain allele is either higher or lower than the expected value given by independent assortment and random association. Linkage disequilibrium

(Mazze, Strock, Simonsen, & Bergenstal, 2004, p. 81). Obesity is another condition which can result in metabolic syndromes which also play a role in the development of T2DM along with other diseases including coronary heart disease, all of which are major contributors to patient morbidity and mortality (Craft & Gordon, 2011, p. 1068).

The molecular basis of FH is described by high allelic heterogeneity. More than 800 molecular flaws have been recognized in the LDLR. Besides, couple of particular mutations in the apo B-100 gene, and in the FH3 genomic locus at 1p34. 1-p32 proprotein convertase subtilisin/kexin type 9 genes (Abifadel et al., 2003) that encodes for neural apoptosis controlled convertase, a distinguished human subtilase that adds to cholesterol homeostasis (Seidah et al., 2003) have been described. Changes in the apo B-100 gene instigate familial ligand-deficient apo B (FLDB) by failure of LDL binding to its receptor and by secondary plasma LDL-cholesterol rise (Whitfield et al., 2004). Proof for a milder biochemical phenotype in patients with FLDB than in patients with FH has been introduced (Pimstone et al.,

FH can either be homozygous or heterozygous, homozygous being more rigorously affected than heterozygous. Heterozygotes have a plasma LDL concentration that is double that of normal individuals, thus increasing the risk of coronary artery disease. Atherosclerosis is the accumulation of white blood cells in the artery walls, thickening it over time. Individuals with two defective copies develop this disease at an early age which usually leads to death. It is always thought that FH is caused by the mutations of the LDL receptor proteins. There are currently more than 800 different mutations for the LDLR that cause FH (Soutar & Naoumova, 2007). The most common types of mutations are premature stop codons, mutations in the promoter and pre-mRNA, and amino acid substitutions. Individuals with autosomal recessive hypercholesterolemia have the same phenotype as the homozygous FH, but the conditions are not as extreme because of the cholesterol and LDL cholesterol levels. Treatment results show better results with lipid-lowering drugs. Some studies show that unaffected individuals and heterozygous individuals how no significant difference (Soutar & Naoumova, 2007). High cholesterol from birth will lead to vascular diseases and hardening of the

They also used a western blot test from crude extracts of the phenotypes to test out the effectiveness of the system, they found that in the reverted flox/flox had the same amount of that of +/+. -/- and geo/geo bot mice both died after 3-4 weeks of birth and the flox/flox were observed to be as healthy as the +/+ and through this -/- and geo/geo were known as the mutants (Sato, 2007). The apical proteins were found to be mislocalized to lysosomes and then degraded in the Rab8 knockout mice, this led to malnutrition as there was poor absorption and digestion of the milk and ultimately killing the mice from starvation. This was found through an experiment determining whether abnormalities in the small intestine were the major cause of death by breeding Flox/+ mice with transgenic mice that express Cre recombinase under the Villin promoter. It was observed that all mouse that expressed one floxed allele died at the same time as the mutant mouse whereas mice with two floxed alleles were healthy but died after 12 weeks of birth due to reduced efficiency of Rab8 (Sato, 2007). The healthy two floxed allele mouse showed a mosaic expression of Rab8, the Rab8 negative cells had large sub-apical vacuoles like the knockout mouse however in the Rab8 positive cells there weren’t any vacuoles. The first experiment is different to other experiment; the first experiment was trying to see what happened

FTO is an important gene to study because it contributes to obesity. Studies in humans and mice have shown that there are strong relationships between FTO

Gene knockdown is the technique where the expression of one or more of an organisms genes are reduced by the mRNA product of a gene being targeted and disrupted so it can’t carry out its normal function which in this case is to produce the BLG protein. The gene knockdown process is carried out by a double stranded RNA molecule (dsRNA) being introduced to the cell that they want to stop the BLG protein made in. The dsRNA is cut into small fragments by a long enzyme called “Dicer”, these small fragments are called interfering RNAs (siRNA). The siRNA bind to special proteins called Argonaute proteins

It is a theory that used to use into public relation.Linkage theory identifies all the type of relationship between different publics and organizations.Linkage theory is coming from a system analysis by Frankelj in 1972.According to Joseph Frankel in his book entitled Contemporary International theory and Behaviour of state in 1972 that he think that linkage is something used to be the beginning of an analysis or a communication.