BIOMAT Database Logo BIOMAT Database Logo

Beta zero thalassemia caused by a base substitution that creates an alternative splice acceptor site in an intron. 1986

J E Metherall, and F S Collins, and J Pan, and S M Weissman, and B G Forget

A thalassemic beta-globin gene cloned from a haplotype I chromosome contains a T to G transversion at position 116 of IVS1 which results in the generation of an abnormal alternative acceptor splice site. Transient expression studies revealed a 4-fold decrease in the amount of RNA produced with greater than 99% of it being abnormally spliced despite preservation of the normal acceptor splice site at position 130. These results suggest that the mutation at IVS1 position 116 results in beta zero thalassemia. A closely related mutation at position 110 of IVS1 also generates a novel acceptor site and results in a similar decrease in total mRNA produced, but approximately 20% of the mRNA produced is normally spliced and thus the phenotype is that of beta + thalassemia. These observations suggest that short range position effects may play a dramatic role in the choice of potential splice acceptor sites. We demonstrate the presence of abnormally spliced mRNA in reticulocytes of affected individuals and show the mutation at IVS1 position 116 segregating from the mutation at IVS1 position 110 in a three generation pedigree. The mutation results in the creation of a MaeI restriction site, as do a number of other thalassemic mutations, and we demonstrate some difficulties that may arise in the differential diagnosis of these mutations.

UI MeSH Term Description Entries
D007438 Introns Sequences of DNA in the genes that are located between the EXONS. They are transcribed along with the exons but are removed from the primary gene transcript by RNA SPLICING to leave mature RNA. Some introns code for separate genes. Intervening Sequences,Sequences, Intervening,Intervening Sequence,Intron,Sequence, Intervening
D009154 Mutation Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations. Mutations
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D003001 Cloning, Molecular The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells. Molecular Cloning
D005796 Genes A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Cistron,Gene,Genetic Materials,Cistrons,Genetic Material,Material, Genetic,Materials, Genetic
D005914 Globins A superfamily of proteins containing the globin fold which is composed of 6-8 alpha helices arranged in a characterstic HEME enclosing structure. Globin
D006367 HeLa Cells The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for, among other things, VIRUS CULTIVATION and PRECLINICAL DRUG EVALUATION assays. Cell, HeLa,Cells, HeLa,HeLa Cell
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000595 Amino Acid Sequence The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION. Protein Structure, Primary,Amino Acid Sequences,Sequence, Amino Acid,Sequences, Amino Acid,Primary Protein Structure,Primary Protein Structures,Protein Structures, Primary,Structure, Primary Protein,Structures, Primary Protein
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

Related Publications

J E Metherall, and F S Collins, and J Pan, and S M Weissman, and B G Forget
Beta-thalassemia resulting from a single nucleotide substitution in an acceptor splice site.
February 1985, Nucleic acids research,
J E Metherall, and F S Collins, and J Pan, and S M Weissman, and B G Forget
Inactivation of an acceptor RNA splice site by a short deletion in beta-thalassemia.
June 1983, The Journal of biological chemistry,
J E Metherall, and F S Collins, and J Pan, and S M Weissman, and B G Forget
Enigmatic rhodopsin mutation creates an exceptionally strong splice acceptor site.
January 2020, Human molecular genetics,
J E Metherall, and F S Collins, and J Pan, and S M Weissman, and B G Forget
An alpha-thalassemia phenotype in a Dutch Hindustani, caused by a new point mutation that creates an alternative splice donor site in the first exon of the alpha2-globin gene.
August 2004, Hemoglobin,
J E Metherall, and F S Collins, and J Pan, and S M Weissman, and B G Forget
Duchenne muscular dystrophy caused by a frame-shift mutation in the acceptor splice site of intron 26.
August 2016, BMC medical genetics,
J E Metherall, and F S Collins, and J Pan, and S M Weissman, and B G Forget
Profound biotinidase deficiency caused by a point mutation that creates a downstream cryptic 3' splice acceptor site within an exon of the human biotinidase gene.
May 1997, Human molecular genetics,
J E Metherall, and F S Collins, and J Pan, and S M Weissman, and B G Forget
Severe Hb S-beta+ thalassemia caused by IVS-I splice site mutations.
July 1998, Hemoglobin,
J E Metherall, and F S Collins, and J Pan, and S M Weissman, and B G Forget
beta-Thalassemia in American Blacks: novel mutations in the "TATA" box and an acceptor splice site.
February 1984, Proceedings of the National Academy of Sciences of the United States of America,
J E Metherall, and F S Collins, and J Pan, and S M Weissman, and B G Forget
The beta zero-thalassemia in an American black family is due to a single nucleotide substitution in the acceptor splice junction of the second intervening sequence.
July 1986, American journal of hematology,
J E Metherall, and F S Collins, and J Pan, and S M Weissman, and B G Forget
Four novel mutations in mucopolysaccharidosis type VII including a unique base substitution in exon 10 of the beta-glucuronidase gene that creates a novel 5'-splice site.
April 1995, Human molecular genetics,
Copied contents to your clipboard!