Genetics and Disease.

Most rheumatic disease are caused by a combination of genes and environment, with genetic variation predisposing or protecting and environmental factors initiating and maintaining a disease state.Variations in genes can occur as single nucleotide polymorphisms in coding or noncoding regions and leading to different alleles. Point mutations are rare variations occurring at less than 1% minor allele frequency. Deletion, insertion, repeated sequences of different lengths, and copy number polymorphisms are also responsible for differences in genes.Haplotypes, blocks of polymorphisms inherited together more often than expected by chance, can be used to identify disease-causing variants and provide information on recombination, population structure, and evolutionary pressures.Association of genes with disease can be performed using linkage studies or association studies. Association studies can determine the odds ratio of a particular gene variant being associated with a particular disease, but require large numbers of samples from affected and unaffected individuals.■ Linkage studies are most useful for monogenic traits with high penetrance where extended family information is available. If a particular gene has only a subtle effect, linkage studies are limited in use. [ABSTRACT FROM AUTHOR]