title: DNAase I hypersensitive site 3' to the beta-globin gene cluster containing two TAA insertions and a G-->A polymorphism is predominantly associated with the beta+-thalassemia IVS-I-6 (T-->C) mutation.
abstract: Analysis of DNA polymorphic sites is an important tool for the detection of gene flow in human evolutionary studies and to study the genetic background for gene mutations. The beta-globin locus contains several single-base restriction fragment length polymorphism (RFLP) sites throughout chromosome 11. In addition to these polymorphic sequence repeats, others are being studied in order to expand our knowledge concerning the role between haplotype-genotype and phenotype associations. Far downstream of the expressed beta-globin genes, there is a hypersensitive site (HS) whose function remains obscure. We sequenced this region in 27 thalassemia patients and found a new pattern in the micro-satellite-like AT-rich region of this site: a new TAA insertion in addition to the one previously described in sickle cell patients with a concomitant polymorphism (G-->A). This new variation was found to be linked to the IVS-I-6 (T-->C) mutation. This polymorphism may be useful for studies concerning genotype and phenotype associations.
authors.affiliation: Haematology and Haemotherapy Centre, State University of Campinas, São Paulo, Brazil.
authors.forename: Juliana T N
authors.initials: JT
authors.lastname: Martins
authors.forename: Silvana
authors.initials: S
authors.lastname: Bordin
authors.forename: Dulcinéia M
authors.initials: DM
authors.lastname: de Albuquerque
authors.forename: Sara T O
authors.initials: ST
authors.lastname: Saad
authors.forename: Fernando F
authors.initials: FF
authors.lastname: Costa
mesh_terms: D004252:DNA Mutational Analysis; D003850:Deoxyribonuclease I; D005260:Female; D005838:Genotype; D005914:Globins; D006801:Humans; D008297:Male; D005810:Multigene Family / Q000235:genetics*; D016254:Mutagenesis, Insertional; D010641:Phenotype; D017354:Point Mutation / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017086:beta-Thalassemia / Q000235:genetics*
chemical_list: D005914:Globins; D003850:Deoxyribonuclease I