In order to study the relationships among mammalian alpha-globin genes, we have determined the sequence of the 3' flanking region of the human alpha 1 globin gene and have made pairwise comparisons between sequenced alpha-globin genes. The flanking regions were examined in detail because sequence matches in these regions could be interpreted with the least complication from the gene duplication...

BACKGROUND The cane toad, Bufo (Chaunus) marinus, is one of the most notorious vertebrate pests introduced into Australia over the last 200 years and, so far, efforts to identify a naturally occurring B. marinus-specific pathogen for use as a biological control agent have been unsuccessful. We explored an alternative approach that entailed genetically modifying a pathogen with broad host specif...

In this article we report a Sardinian family, in which a beta-thalassemia gene and a triple alpha-globin loci, counterpart of the rightward deletion type alpha-thalassemia-2, were segregating. The analysis of the genotype-phenotype correlations in the different family members allowed us to give an outline of the manifestations associated with different genotype combinations. The heterozygote fo...

The human beta-globin gene complex spans a region of 70 kb and contains numerous sequence variants. These variant sites form a 5' cluster (5' beta-haplotype) and a 3' cluster (3' beta-haplotype) with strong linkage disequilibrium among the sites within each cluster, but not between the two clusters. The 9-kb region between the 5' and 3' clusters has been estimated to have rates of recombination...

Complementary DNA, transcribed in vitro from purified rabbit globin messenger RNA and made double-stranded, has been inserted into Escherichia coli plasmids pSC101 and pMB9 by the poly(dT)/poly(dA) "tailing" and annealing technique. E. coli transformants given by this DNA preparation have been shown to contain globin sequences by the hybridization of globin RNA to DNA from clones grown and lyse...

M13 DNA probes labeled with biotinylated psoralen and a streptavidin-horseradish peroxidase conjugate provide nonradioactive detection of the sickle cell and normal alleles of the beta-globin locus. The two biotinylated probes contain single-stranded sequences complementary to two different Sau3AI restriction fragments from the 5' region of the beta-globin gene and double-stranded M13 vector se...

To explore the relationships between transcription, messenger RNA (mRNA) processing, and nuclear structure, ribonucleoprotein particles containing heterogeneous nuclear RNA (hnRNP) have been purified from globin-producing mouse Friend erythroleukemia cells. These nuclear hnRNP particles sediment at 50S-200S and contain, in addition to high molecular weight hnRNA, a specific set of nuclear prote...

Specific DNA sequences were loaclized in the nuclei of paraffin-embedded mouse tissue sections with in situ hybridization using a biotinylated globin probe in conjunction with a streptavidin-alkaline phosphatase detection system. Globin inserts were clearly detected in the tissue sections of transgenic mice containing 1000, 120 or 5 copies of the exogenously introduced beta-globin genes. In add...

We have investigated the DNase I hypersensitivity of a hybrid mouse/human beta-globin gene in erythroid and non-erythroid cells of transgenic mice, to examine the relationship between the chromatin structure and the expression of an exogenous gene. The hybrid globin gene was previously shown to be expressed specifically in erythroid cells in some transgenic lines. The maximal level of hybrid gl...

Reactivation of fetal hemoglobin (HbF) expression using pharmacological agents represents a potential strategy for the therapy of beta-thalassemia, sickle cell disease, HbE and other beta-hemoglobinopathies. However, the drugs currently available have low efficacy and specificity and are associated with high toxicity. We describe the development of stable cellular genomic reporter assays (GRAs)...