科研之友
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摘要
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- and beta-globin genes' deficiencies and abnormalities. Normal ratios are 2.75+/-0.16 (alpha 2/alpha 1) and 4.40+/-0.25 (alpha/beta). Higher alpha/beta ratios are found in beta-thal heterozygotes with transcriptional mutants (similar to 6.7) and nonsense or frameshift mutants in the first or second exon (7.5-8.0). Exon 3 mutants causing dominant beta-thal thrait have a lower alpha/beta ratio (similar to 6.0); the mutant mRNA can be detected and is present in decreased quantities. RNA processing mutants are generally associated with high alpha/beta ratios (average 7.0 in heterozygotes) except for the IVS-I-110 (G-->A) mutation. Deletional mutants involving the entire beta-globin gene have surprisingly low alpha/beta ratios (4.8-5.4). Abnormal Hb heterozygotes have normal alpha/beta ratios (4.23+/-0.03 for those with stable Hb variants and 4.28+/-0.22 for those with unstable Hb variants). These data suggest a normal stability for the Qbx-mRNA and exclude the possibility that an unstable mRNA is a contributing factor to the hematological abnormalities observed in the unstable Hb hemolytic anemia. Thus, the instability of the abnormal globin chain or the Hb type in which it is incorporated appears to be the major cause of hemolytic disease in these subjects. Loss of one a gene decreases alpha 2/alpha 1 to similar to 1.6 and 0, and alpha/beta to similar to 3.8 and similar to 1.5 for -alpha/alpha alpha and -alpha/-alpha, respectively. Significant differences are observed between the deletional types (--/-alpha; alpha 2/alpha 1 ratio of zero; alpha/beta ratio of similar to 1) and non-deletional types (--/alpha(T) alpha; alpha 2/alpha 1 ratio of 0.05-0.3 for those with T=the 5 nt deletion or the terminating codon mutant, and similar to 1.0 for those with T=a poly(A) mutation; alpha/beta ratio in all types of similar to 0.7) of the Hb H disease. Comparable data are found for the non-deletional alpha-thal-2 homozygotes. These data are in agreement with the variability of clinical presentation of the Hb H disease. The determination of the two ratios may be diagnostically of considerable value.
- 出版日期1997-10
