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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Genetic effects on susceptibility, clinical expression, and treatment outcome of type 1 autoimmune hepatitis.

Currently, three genetic factors have been short-listed as possible modulators of susceptibility and severity in type 1 AIH. They are female sex, HLA DRB alleles encoding lysine at position DR beta 71, and the CTLA4*G allele. The fourth association (i.e., TNFRSF6) remains to be confirmed. There are many other candidates to investigate. Current hypotheses suggest that the autoimmune genotype will include multiple (some linked, others discrete) loci which make a permissive background. Not all "at risk" individuals will develop clinical disease, and selection will depend on the interaction of this "permissive gene pool" (i.e., the host) with the environment. The resulting autoimmune phenotype will depend on gene dose and gene interaction. The human genome project has presented medical science with the challenge to identify the genes that determine common human diseases, including autoimmunity [1]. Although type 1 AIH is considerably less common than diabetes or RA, it may serve as a useful model for other autoimmune diseases. Diagnosis depends on histologic findings, and liver biopsy examinations are part of the usual assessment strategy in type 1 AIH. The availability of these tissue specimens provides a clear basis for monitoring disease progression and may permit investigators to study the impact of genetic polymorphism on disease activity. The emergence of high throughput technologies will significantly enhance our ability to study the interactions between constellations of polymorphic genes and both disease expression and behavior. An abundance of polymorphism is found in the genome. In many diseases, functional studies and genome scanning have helped revise and reduce the list of candidates. Affected families are rare in type 1 AIH, and patients are at risk if corticosteroid treatment is withheld. Under these circumstances, genetic studies may be the most practical, low risk means to investigate the pathogenesis of type 1 AIH and many other autoimmune diseases.[1]


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