title: A human-specific polymorphism in the coding region of the aggrecan gene. Variable number of tandem repeats produce a range of core protein sizes in the general population.
abstract: Aggrecan, one of the major structural genes of cartilage, encodes a proteoglycan core protein composed of an extended central glycosaminoglycan-bearing domain, flanked by globular domains at each end. The central region consists of long stretches of repeating amino acids that serve as attachment sites for glycosaminoglycans such as chondroitin and keratan sulfate; the terminal globular domains interact with other cartilage components. The glycosaminoglycan attachment region is encoded in several species by a single large exon, within which are several different types of repeating sequences. Several species show within this exon a similar block of conserved repeats for attachment of chondroitin sulfate, but in humans this group of repeats is particularly well conserved. Examination of genomic DNA from a population of unrelated individuals by polymerase chain reaction or Southern blot assays shows this block of repeat sequences exists in multiple allelic forms, which differ by the number of repeats at this site in each allele. Thirteen different alleles have been identified, with repeat numbers ranging from 13 to 33. This is an unusual example of an expressed variable number of tandem repeat polymorphism. This polymorphism is apparently restricted to humans, of several species examined. This polymorphism results in individuals with differing length aggrecan core proteins, bearing different numbers of potential attachment sites for chondroitin sulfate. The possibility exists for a molecular understanding of biological variation in cartilage functional properties.
authors.affiliation: Shriners Hospital for Children, Portland, Oregon 97210, USA. kjd@shcc.org
authors.forename: K J
authors.initials: KJ
authors.lastname: Doege
authors.forename: S N
authors.initials: SN
authors.lastname: Coulter
authors.forename: L M
authors.initials: LM
authors.lastname: Meek
authors.forename: K
authors.initials: K
authors.lastname: Maslen
authors.forename: J G
authors.initials: JG
authors.lastname: Wood
mesh_terms: D053674:Aggrecans; D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D011508:Chondroitin Sulfate Proteoglycans / Q000235:genetics*; D015342:DNA Probes / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D015252:Deoxyribonucleases, Type II Site-Specific / Q000378:metabolism; D016326:Extracellular Matrix Proteins; D006801:Humans; D037181:Lectins, C-Type; D018598:Minisatellite Repeats; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011509:Proteoglycans / Q000235:genetics*; D051381:Rats; D017422:Sequence Analysis, DNA
chemical_list: C508321:Acan protein, rat; D053674:Aggrecans; D011508:Chondroitin Sulfate Proteoglycans; D015342:DNA Probes; D018076:DNA, Complementary; D016326:Extracellular Matrix Proteins; D037181:Lectins, C-Type; D011509:Proteoglycans; D015252:Deoxyribonucleases, Type II Site-Specific; C024403:GGCC-specific type II deoxyribonucleases