User:Tcs46/sandbox

Proposed Edits for Celiac Disease
''' 2 hypotheses concerning the high prevalence of CD in Caucasians: 1)	Due to random chance (genetic drift) 2)	The genes responsible for CD have continued on due to positive selection for another positive trait

Using a haplotype similarity test 4 out of the network of 40 CD related genes showed a positive selection. However, the DQ2.5 haplotype did not show a preference for positive selection meaning that CD itself is not/was not an adaptive trait. However, the four genes identified above are also risk factors for other diseases such as Crohn’s, Type 1 diabetes, and other autoimmune/inflammatory diseases.

One particular loci, SH2B3 when in a homozygous individual, allows for a higher concentration of cytokines responsible for inflammatory responses. This observation further supports that the four loci with a positive selection may play a role in fighting infection but makes individuals more susceptible to autoimmune diseases like coeliac.

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These are my proposed edits as of 10/30

The prevalence of CD genotypes in the modern population is not completely understood. Given the characteristics of the disease and its apparent strong heritability, it would normally be expected that the genotypes would undergo negative selection and to be absent in societies where agriculture has been practised the longest (compare with a similar condition, Lactose intolerance, which has been negatively selected so strongly that its prevalence went from ~100% in ancestral populations to less than 5% in some European countries). This expectation was first proposed by Simoons (1981). By now, however, it is apparent that this is not the case; on the contrary, there is evidence of positive selection in CD genotypes. The DQ2.5 haplotype, in certain tests did not show a preference for positive selection but, 4 out of the network of 40 CD related genes showed a positive selection. The four genes are also risk factors for other diseases such as Crohn’s, Type 1 diabetes, and other autoimmune/inflammatory diseases. It is suspected that some of them may have been beneficial by providing protection against bacterial infections. One particular loci, SH2B3 when in a homozygous patient, allows for a higher concentration of cytokines responsible for inflammatory responses. This observation further suggests that the four loci with a positive selection may play a role in fighting infection but makes individuals more susceptible to autoimmune diseases like coeliac.

I'm still working on the formatting of the references. This is mostly from the following:

107. Abadie, V., Sollid, L., Barreiro, L., & Jabri, B. (2011). Integration of Genetic and Immunological Insights into a model of Celiac Disease Pathogenesis. Annual Review of Immunology, 493-525.

108. Rubio-Tapia, A., Ludvigsson, J. F., Brantner, T. L., & Murray, J. A. (2012). The Prevalence of Celiac Disease in the United States. The American Journal of Gastroenterology, 1538-1544.

Tcs46 (talk) 00:49, 25 October 2013 (UTC)