[HTML][HTML] Genetic analysis of autoimmune disease

TJ Vyse, JA Todd - Cell, 1996 - cell.com
TJ Vyse, JA Todd
Cell, 1996cell.com
The destruction or disruption of the body's own tissues by the immune system results from a
complex interaction of genetic and environmental factors. Inbred populations such as
laboratory strains of mice and rats and outbred populations such as humans harbor a pool of
DNA mutations or allelic variants that affect the expression/function of genes involved in
control of the immune response. Individually, most mutations in the genome have mild, if not
undetectable, effects, but in combination with “normal” alleles of other loci produce a …
The destruction or disruption of the body's own tissues by the immune system results from a complex interaction of genetic and environmental factors. Inbred populations such as laboratory strains of mice and rats and outbred populations such as humans harbor a pool of DNA mutations or allelic variants that affect the expression/function of genes involved in control of the immune response. Individually, most mutations in the genome have mild, if not undetectable, effects, but in combination with “normal” alleles of other loci produce a measurable and occasionally lethal autoimmune phenotype. Many of these mutations may be normal variants, which in other circumstances act to maintain the health of the individual. They may have subtle quantitative effects, bestowing a relatively small risk of disease. We refer to primary, predisposing allelic variants as “etiological mutations” to distinguish them from other polymorphisms that play no direct role in disease. It is emphasized that the term mutation is used here generically and is not meant to infer function. The incomplete risk conferred by any single allele makes both the mapping and final identification of these etiological mutations difficult. This single characteristic is the main reason why most common diseases such as autoimmune conditions are not inherited in a simple Mendelian way, but instead have a complex or unknown mode of inheritance. Identification of these etiological mutations and an understanding of their functional consequences will impact the diagnosis, treatment, and prevention of autoimmune diseases, which affect about 4% of the population (see Table 1).
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