title: The alpha / beta and alpha 2 / alpha 1-globin mRNA ratios in different forms of alpha-thalassemia.
abstract: The present study provides information about the alpha / beta and alpha 2 / alpha 1-mRNA ratios in reticulocytes of normal adults and individuals with different alpha-globin gene deficiencies; it found its origin in analytical data of blood samples from a Laotian couple and their newborn baby. The father carried the 4.2 kb deletion on one chromosome and a TAA --> CAA mutation at the terminating codon of the alpha 2 gene (Hb Constant Spring or CS) on the other chromosome. The mother had the 3.7 kb deletion on one chromosome and a TA A --> TAT mutation at the terminating codon of the alpha 2-globin gene (Hb Paksé) of the second chromosome. The baby was a compound heterozygote for the two termination codon mutations. The mRNA data for this family were compared to those for persons with several well-defined alpha-globin gene deficiencies. The results confirm the importance of the alpha 2 alpha 1-mRNA for the synthesis of alpha chains in alpha-thalassemia-2 homozygotes (-alpha/-alpha) and in patients with Hb H disease due to the deletion of three alpha-globin genes (-alpha/--). Furthermore, the MRNA production of the alpha 1-globin gene on the chromosome with the alpha CS mutation (alpha CS alpha) is only one-half of that by the alpha 2 alpha 1-globin gene of a chromosome with a 3.7 or 4.2 kb deletion, explaining the greater severity of, and higher Hb H level in Hb H patients with the alpha CS alpha condition (alpha CS alpha/--) as compared to those with the three gene deletion (-alpha/--). The methodology could be useful as a preliminary screening for the presence of point mutations leading to the functional loss of a single alpha-globin gene, provided common deletional alleles have been excluded.
authors.affiliation: Laboratory of Protein Chemistry, Medical College of Georgia, Augusta 30912-2100, USA.
authors.forename: N S
authors.initials: NS
authors.lastname: Smetanina
authors.forename: J Y
authors.initials: JY
authors.lastname: Leonova
authors.forename: N
authors.initials: N
authors.lastname: Levy
authors.forename: T H
authors.initials: TH
authors.lastname: Huisman
mesh_terms: D000328:Adult; D001483:Base Sequence; D003062:Codon / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation; D005838:Genotype; D005914:Globins / Q000096:biosynthesis / Q000235:genetics*; D006447:Hemoglobin H / Q000235:genetics; D006455:Hemoglobins, Abnormal / Q000235:genetics; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008969:Molecular Sequence Data; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics; D012156:Reticulocytes / Q000737:chemistry; D017384:Sequence Deletion; D017085:alpha-Thalassemia / Q000097:blood / Q000145:classification / Q000235:genetics*
chemical_list: D003062:Codon; D006455:Hemoglobins, Abnormal; D012333:RNA, Messenger; C099132:hemoglobin Pakse; C049214:hemoglobin Q Thailand; D005914:Globins; D006447:Hemoglobin H; C035541:Hemoglobin Constant Spring