{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T15:22:29Z","timestamp":1776007349785,"version":"3.50.1"},"reference-count":52,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2005,4,14]],"date-time":"2005-04-14T00:00:00Z","timestamp":1113436800000},"content-version":"vor","delay-in-days":3025,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Electrophoresis"],"published-print":{"date-parts":[[1997,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Simple repetitive DNA sequences are abundantly interspersed in eukaryote genomes and therefore useful in genome research and genetic fingerprinting in plants, fungi and animals, including man. Recently, simple repeats were also identified in some prokaryotic genomes. Hence the same probes can be applied for multilocus DNA fingerprinting in medically relevant bacteria. Simple repeats including composite dinucleotide microsatellites are differentially represented in different compartments of eukaryote genomes. Expanded triplet blocks in and around certain genes may, for example, cause so\u2010called trinucleotide diseases in man. As a consequence, simple repetitive sequences should also be characterized with respect to their influences on the DNA structure, gene expression, genomic (in)stability and their development on an evolutionary time scale. Here three examples of microsatellites in the human major histocompatibility complex (HLA) are investigated, a (GT)<jats:sub>n<\/jats:sub> microsatellite situated 2 kb 5\u2032 off the lymphotoxin \u03b1 (LTA) gene, a (GAA)<jats:sub>n<\/jats:sub> block in the 5\u2032 part of the <jats:italic>HLA\u2010F<\/jats:italic> gene and a composite (GT)<jats:sub>n<\/jats:sub>(GA)<jats:sub>m<\/jats:sub> stretch in the second intron of <jats:italic>HLA\u2010DRBl<\/jats:italic> genes. Grossly differing mutation rates are evident in these elements as well as varying linkage disequilibria. The unfolding of these simple repeats in distant human populations is covered including Caucasians, Bushmen and South American Indians. Furthermore, implications of simple repeat neighboring genes are discussed for the multifactorial diseases multiple sclerosis (MS), rheumatoid arthritis (RA) and early onset pauciarticular arthritis (EOPA). Polymorphisms of <jats:italic>HLA\u2010DRBl<\/jats:italic> and T cell receptor \u03b2 variable (<jats:italic>TCRBV<\/jats:italic>) genes confer susceptibility for these autoimmune diseases as demonstrable by intronic simple repeat variability. Microsatellite polymorphisms within the <jats:italic>TNF<\/jats:italic> region reveal linkage disequilibria with <jats:italic>HLA\u2010DRBl<\/jats:italic> and different promotor alleles of the <jats:italic>TNFA<\/jats:italic> gene. Disease associations with <jats:italic>TNFA<\/jats:italic> microsatellite alleles are, on the one hand, secondary to associations with <jats:italic>HLA\u2010DRBl<\/jats:italic> genes (in MS) or they represent additional risk factors (in RA, EOPA) on the other hand. Evolutionary persistence, various structural conformations and the specific binding of nuclear proteins to several simple repeat sequences refute the preconceptions of biological insignificance for all of these ubiquitously interspersed elements.<\/jats:p>","DOI":"10.1002\/elps.1150180916","type":"journal-article","created":{"date-parts":[[2005,5,28]],"date-time":"2005-05-28T12:15:43Z","timestamp":1117282543000},"page":"1577-1585","source":"Crossref","is-referenced-by-count":32,"title":["On simple repetitive DNA sequences and complex diseases"],"prefix":"10.1002","volume":"18","author":[{"given":"Cornelia","family":"Epplen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eduardo J. 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