Predicting human minisatellite polymorphism.

France Denoeud (1) , Gilles Vergnaud (2, 3) , Gary Benson (4)

1 UMR 8030 - Génomique métabolique
2 ENSTA Paris - École Nationale Supérieure de Techniques Avancées
3 IGM - Institut de génétique et microbiologie [Orsay]
4 GI Unit

We seek to define sequence-based predictive criteria to identify polymorphic and hypermutable minisatellites in the human genome. Polymorphism of a representative pool of minisatellites, selected from human chromosomes 21 and 22, was experimentally measured by PCR typing in a population of unrelated individuals. Two predictive approaches were tested. One uses simple repeat characteristics (e.g., unit length, copy number, nucleotide bias) and a more complex measure, termed HistoryR, based on the presence of variant motifs in the tandem array. We find that HistoryR and percentage of GC are strongly correlated with polymorphism and, as predictive criteria, reduce by half the number of repeats to type while enriching the proportion with heterozygosity >/=0.5, from a background level of 43% to 59%. The second approach uses length differences between minisatellites in the two releases of the human genome sequence (from the public consortium and Celera). As a predictor, this similarly enriches the number of polymorphic minisatellites, but fails to identify an unexpectedly large number of these. Finally, typing of the highly polymorphic minisatellites in large families identified one new hypermutable minisatellite, located in a predicted coding sequence. This may represent the first coding human hypermutable minisatellite.

Domaines: Sciences du Vivant [q-bio]; Génétique; Médecine humaine et pathologie

France Denoeud, Gilles Vergnaud, Gary Benson. Predicting human minisatellite polymorphism.. Genome Research, 2003, 13 (5), pp.856-67. ⟨hal-01158326⟩