The duplicated human alpha globin genes lie close together in cellular DNA.

Orkin, Stuart H.

doi:10.1073/pnas.75.12.5950

Cited by 159 publications

(38 citation statements)

References 24 publications

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“…The a-globin cluster consists of five genes and pseudogenes organized over a 30-kilobase (kb)' distance in the order: 5't-i/'{-i/'a-a2-a 1 (3). The two adjacent a-globin genes, a 1 and a2, are located 3.7 kb apart and each is situated within a segment of duplicated DNA (3)(4)(5). During primate evolution the sequence composition of these duplicated segments encompassing the two a-globin genes has changed in parallel (6,7).…”

Section: Introductionmentioning

confidence: 99%

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

Liebhaber¹,

Cash²,

Main³

1985

J. Clin. Invest.

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a-Globin is encoded by the two adjacent genes, al and a2. Although it is clearly established that both a-globin genes are expressed, their relative contributions to a-globin messenger RNA (mRNA) and protein synthesis are not fully defined. Furthermore, changes that may occur in a-globin gene activity secondarily to the loss of function of one or more of these genes (a-thalassemia [Thall) have not been directly investigated. This study further defines the expression of the two human a-globin genes by determining the relative levels of al and a2 mRNA in the reticulocytes of normal individuals and in individuals heterozygous for the common 3.7-kilobase deletion within the a-globin gene cluster that removes the a2-globin gene (the rightward type aThal-2 deletion). To quantitate accurately the ratio of the two a-globin mRNAs, we have modified a previously reported S1 nuclease assay to include the use of 32P end-labeled probes isolated from al-and a2-globin complementary DNA recombinant plasmids. In individuals with a normal a-globin genotype (as determined by Southern blot analysis Iaa/aal), a2-globin mRNA is present at an average 2.8-fold excess to al. In individuals heterozygous for the rightward type a-Thal-2 deletion (-a/aa) the ct2/al mRNA ratio is 1:1. These results suggest that the loss of the a2-globin gene in the a-Thal-2 deletion is associated with a 1.8-fold compensatory increase al-globin gene expression.

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Section: Introductionmentioning

confidence: 99%

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

Liebhaber¹,

Cash²,

Main³

1985

J. Clin. Invest.

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“…The plasmid was cultured and isolated (10) (12). Thus, nonthalassemic subjects had such a fragment on both chromosomes, whereas Chinese subjects with a-thalassemia-1 and the nondeletion type ofhemoglobin-H disease had these two loci on a single chromosome.…”

Section: Introductionmentioning

confidence: 99%

Organization of the alpha-globin genes in the Chinese alpha-thalassemia syndromes.

Embury¹,

Lebo²,

Dozy³

et al. 1979

J. Clin. Invest.

174

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“…Most commonly the lesions causing a-thalassemia-1 and a-thalassemia-2 result from deletion of both (--) or one (-a) of the duplicated a-globin structural loci respectively (1,13,15,18,19). Less frequently a-thalassemia-2 is produced by non-deletion defects (3,5,8,14,16).…”

Section: Rbc Red Blood Cell Sea South East Asian Patientsmentioning

confidence: 99%

Longitudinal Study of a Newborn with a Combination of Deletion and Nondeletion α-Thalassemia-2

et al. 1984

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SummaryIn this study we have characterized by DNA analysis the molecular basis of an a-thalassemia condition found in an infant, with 16% Hb Bart's at birth, who developed an hematologic picture similar to the a-thalassemia carrier state. Restriction endonuclease analysis and hybridization with a and ( specific probes have provided strong evidence that this patient carries a genetic compound of deletion a-thalassemia-2 lesion (-a) and a non-deletion defect ( (~c x ) '~] with both a-structural genes intact on chromosome 16. He inherited the deletion a-thalassemia-2 chromosome (-a) from the father and the chromosome with nondeletion a-thalassemia defect from the mother. Because the deletion of one, two, or three a-globin structural genes is associated with 1-2%, 5-6%, or 25%, Hb Bart's respectively, these findings suggest that the non-deletion chromosome ((c~a)'~] contains two a-globin structural genes that are less active than a single a gene (-a).

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The duplicated human alpha globin genes lie close together in cellular DNA.

Cited by 159 publications

References 24 publications

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

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

Organization of the alpha-globin genes in the Chinese alpha-thalassemia syndromes.

Longitudinal Study of a Newborn with a Combination of Deletion and Nondeletion α-Thalassemia-2

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