title: Repeat expansion in spinocerebellar ataxia type 17 alleles of the TATA-box binding protein gene: an evolutionary approach.
abstract: The variability and mutational changes of the CAG microsatellite in the TATA-box binding protein gene (TBP) were studied. We sequenced the microsatellite of the TBP gene of 25 unrelated individuals from northern Germany (10 SCA17 patients and 15 unaffected control individuals). In addition, the microsatellites were sequenced from individuals of 10 northern German families with at least one family member affected by SCA17. To study also the evolutionary history of this CAG/CAA microsatellite in nonhuman primates, the homologous regions were analysed from Pan troglodytes, Gorilla gorilla, Pongo pygmaeus, P. abellii, Hylobates lar, Nomascus leucogenys, Symphalangus syndactylus, Macaca mulatta, Papio hamadryas, Colobus polykomos and Callithrix jacchus. Three major conclusions were drawn: (i) Patterns of synonymous CAA interruptions in the microsatellite are characteristic and likely to result from selection for stabilizing the repetitive region; (ii) Interspecific comparisons indicate that SCA17 is likely to be a human trait. The most common allele in humans (37 repeats) is close to the threshold value upon which neurodegenerative changes can occur and may act as a repository for expanded, pathogenic alleles; (iii) The cassette-like structure of five out of 17 expanded alleles can be attributed to unequal crossing over. This can explain the rare and sporadic de novo generation of SCA17 alleles.
authors.affiliation: Department of Medical Genetics, Division of General Human Genetics, Institute of Human Genetics, University of Tübingen, Tübingen, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Tomiuk
authors.forename: Lutz
authors.initials: L
authors.lastname: Bachmann
authors.forename: Claudia
authors.initials: C
authors.lastname: Bauer
authors.forename: Arndt
authors.initials: A
authors.lastname: Rolfs
authors.forename: Ludger
authors.initials: L
authors.lastname: Schöls
authors.forename: Christian
authors.initials: C
authors.lastname: Roos
authors.forename: Hans
authors.initials: H
authors.lastname: Zischler
authors.forename: Mathias M
authors.initials: MM
authors.lastname: Schuler
authors.forename: Silke
authors.initials: S
authors.lastname: Bruntner
authors.forename: Olaf
authors.initials: O
authors.lastname: Riess
authors.forename: Peter
authors.initials: P
authors.lastname: Bauer
mesh_terms: D000818:Animals; D003198:Computer Simulation; D019143:Evolution, Molecular; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008297:Male; D011323:Primates / Q000235:genetics*; D020754:Spinocerebellar Ataxias / Q000235:genetics*; D035181:TATA-Box Binding Protein / Q000235:genetics*; D019680:Trinucleotide Repeat Expansion
chemical_list: D035181:TATA-Box Binding Protein