RGD Reference Report - Compensatory increase in alpha 1-globin gene expression in individuals heterozygous for the alpha-thalassemia-2 deletion. - Rat Genome Database

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Compensatory increase in alpha 1-globin gene expression in individuals heterozygous for the alpha-thalassemia-2 deletion.

Authors: Liebhaber, SA  Cash, FE  Main, DM 
Citation: Liebhaber SA, etal., J Clin Invest. 1985 Sep;76(3):1057-64.
RGD ID: 10449442
Pubmed: PMID:4044827   (View Abstract at PubMed)
PMCID: PMC423986   (View Article at PubMed Central)
DOI: DOI:10.1172/JCI112058   (Journal Full-text)

alpha-Globin is encoded by the two adjacent genes, alpha 1 and alpha 2. Although it is clearly established that both alpha-globin genes are expressed, their relative contributions to alpha-globin messenger RNA (mRNA) and protein synthesis are not fully defined. Furthermore, changes that may occur in alpha-globin gene activity secondarily to the loss of function of one or more of these genes (alpha-thalassemia [Thal]) have not been directly investigated. This study further defines the expression of the two human alpha-globin genes by determining the relative levels of alpha 1 and alpha 2 mRNA in the reticulocytes of normal individuals and in individuals heterozygous for the common 3.7-kilobase deletion within the alpha-globin gene cluster that removes the alpha 2-globin gene (the rightward type alpha-Thal-2 deletion). To quantitate accurately the ratio of the two alpha-globin mRNAs, we have modified a previously reported S1 nuclease assay to include the use of 32P end-labeled probes isolated from alpha 1- and alpha 2-globin complementary DNA recombinant plasmids. In individuals with a normal alpha-globin genotype (as determined by Southern blot analysis [alpha alpha/alpha alpha]), alpha 2-globin mRNA is present at an average 2.8-fold excess to alpha 1. In individuals heterozygous for the rightward type alpha-Thal-2 deletion (-alpha/alpha alpha) the alpha 2/alpha 1 mRNA ratio is 1:1. These results suggest that the loss of the alpha 2-globin gene in the alpha-Thal-2 deletion is associated with a 1.8-fold compensatory increase alpha 1-globin gene expression.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
alpha thalassemia  IEP 10449442; 10449442 RGD 
alpha thalassemia  ISOHBA2 (Homo sapiens)10449442; 10449442 RGD 
alpha thalassemia  ISOHBA1 (Homo sapiens)10449442; 10449442 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Hba-a1  (hemoglobin alpha, adult chain 1)
Hba-a2  (hemoglobin alpha, adult chain 2)

Genes (Mus musculus)
Hba-a1  (hemoglobin alpha, adult chain 1)
Hba-a2  (hemoglobin alpha, adult chain 2)

Genes (Homo sapiens)
HBA1  (hemoglobin subunit alpha 1)
HBA2  (hemoglobin subunit alpha 2)


Additional Information