SCD is a group of inherited red blood cell disorders. Healthy red blood cells are round, and they move through small blood vessels to carry oxygen to all parts of the body. The sickle cells die early, which causes a constant shortage of red blood cells. Also, when they travel through small blood vessels, they get stuck and clog the blood flow.
This can cause pain and other serious problems such infection, acute chest syndrome and stroke. This is commonly called sickle cell anemia and is usually the most severe form of the disease. Hemoglobin is a protein that allows red blood cells to carry oxygen to all parts of the body. This is usually a milder form of SCD. Did you know SCD affects people from many parts of the world?
The severity of these rarer types of SCD varies. This is called sickle cell trait SCT. People with SCT usually do not have any of the signs of the disease and live a normal life, but they can pass the trait on to their children. Additionally, there are a few, uncommon health problems that may potentially be related to sickle cell trait. SCD is a genetic condition that is present at birth. The targeting construct contained 1. Fabry et al. Previous transgenic models had expressed residual levels of mouse globins which complicated the interpretation of experimental results.
These mice were created by breeding the alpha-globin-knockout mouse and the mouse with deletion of the beta major -deletion to homozygosity, the same mice expressing human alpha- and beta S -transgenes see The animals were considered important for testing strategies for gene therapy and for testing new noninvasive diagnostic procedures such as magnetic resonance imaging techniques.
Ryan et al. In both cases the model was produced by mating transgenic mice that expressed human sickle hemoglobin with mice having knockout mutations of the mouse alpha- and beta-globin genes.
Similar to human patients with sickle cell disease, the mice developed hemolytic anemia and extensive organ pathology. Although chronically anemic, most animals survived 2 to 9 months and were fertile. Thus, this mouse model of sickle cell disease should be useful for trial of drug and genetic therapies. Chang et al.
The transgenic lines were produced by coinjection of human alpha-, gamma-, and beta-globin constructs. Thus, all of the transgenes were integrated at a single chromosomal site. Studies in transgenic mice had demonstrated that the normal gene order and spatial organization of the members of the human beta-globin gene family are required for appropriate developmental and stage-restricted expression of the genes.
The rationale was that the high oxygen affinity hemoglobin, the lower oxygen affinity of HbS Antilles, and the lower solubility of deoxygenated HbS Antilles than HbS would favor deoxygenation and polymerization of human HbS Antilles in the red cells of the high-oxygen-affinity mice.
The mice exhibited reticulocytosis, an elevated white blood cell count, and lung and kidney pathology commonly found in sickle cell patients, which should make these mice useful for experimental studies on possible therapeutic intervention of sickle cell disease.
Using a transgenic mouse model of sickle cell disease, Blouin et al. He and Russell generated complex transgenic knockout mice expressing human hemoglobin-S, either exclusively S-alpha mice or in the presence of human zeta-globin S-zeta mice , an endogenous, developmentally silenced, non-beta-like globin. Sickle-cell disease-related deficits in erythrocyte number, hematocrit, and total hemoglobin were significantly improved in S-zeta mice.
They also had reduced spleen size and improved urine concentrating ability compared with S-alpha mice. Hanna et al. This was achieved after correction of the human sickle hemoglobin allele by gene-specific targeting. The authors pointed out the problems associated with using retroviruses and oncogenes for reprogramming need to be resolved before iPS cells can be considered for human therapy. Thus, Xu et al. Savitt and Goldberg gave an interesting account of investigations into the story of Walter Clement Noel, the first-to-be-described case of sickle cell anemia Herrick, Irons, a year-old intern, obtained a history and performed routine physical, blood, and urine examinations.
He noticed that Noel's blood smear contained 'many pear-shaped and elongated forms' and alerted his attending physician, James B. Herrick, to the unusual blood findings. Irons drew a rough sketch of these erythrocytes in the hospital record.
Herrick and Irons followed Noel over the next 2. Thereafter, Noel returned to Grenada to practice dentistry. He died 9 years later at the age of Curiously, Irons, who lived from to , was not included by Herrick, who lived from to , in the authorship.
Conner et al. DNA from normal homozygotes showed hybridization only for the first probe; DNA from persons with sickle cell anemia showed hybridization only with the second; DNA from sickle cell anemia heterozygotes showed hybridization with both.
Allele-specific hybridization of oligonucleotides was proposed as a general method for diagnosis of any genetic disease which involves a point mutation in a single-copy gene. Saiki et al. It combines 2 methods: primer-mediated enzymatic amplification about , times of specific beta-globin target sequences in genomic DNA and restriction endonuclease digestion of an end-labeled oligonucleotide probe hybridized in solution to the amplified beta-globin sequences.
In less than a day and with much less than a microgram of DNA, the diagnosis can be made. Adams, R. Sickle cell disease and stroke. Editorial J. Child Neurol. Adler, B. Fatal sickle cell crisis after granulocyte colony-stimulating factor administration.
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Chang, J. Transgenic knockout mice exclusively expressing human hemoglobin S after transfer of a kb beta-S-globin yeast artificial chromosome: a mouse model of sickle cell anemia. Charache, S. Hydroxyurea and sickle cell anemia: clinical utility of a myelosuppressive 'switching' agent. Medicine , Treatment of sickle cell anemia with 5-azacytidine results in increased fetal hemoglobin production and is associated with nonrandom hypomethylation of DNA around the gamma-delta-beta-globin gene complex.
Effect of hydroxyurea on the frequency of painful crises in sickle cell anemia. New Eng. Cheung, M. Prenatal diagnosis of sickle cell anaemia and thalassaemia by analysis of fetal cells in maternal blood. Nature Genet. Conner, B. Detection of sickle cell beta S -globin allele by hybridization with synthetic oligonucleotides. Dover, G. Hydroxyurea induction of hemoglobin F production in sickle cell disease: relationship between cytotoxicity and F cell production. Blood , Esrick, E.
Post-transcriptional genetic silencing of BCL11A to treat sickle cell disease. Fabry, M. Magnetic resonance evidence of hypoxia in a homozygous alpha-knockout of a transgenic mouse model for sickle cell disease.
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The HBB gene provides instructions for making beta-globin. Various versions of beta-globin result from different mutations in the HBB gene. HBB gene mutations can also result in an unusually low level of beta-globin; this abnormality is called beta thalassemia.
In people with sickle cell disease, at least one of the beta-globin subunits in hemoglobin is replaced with hemoglobin S. In sickle cell anemia also called homozygous sickle cell disease , which is the most common form of sickle cell disease, hemoglobin S replaces both beta-globin subunits in hemoglobin. In other types of sickle cell disease, just one beta-globin subunit in hemoglobin is replaced with hemoglobin S. The other beta-globin subunit is replaced with a different abnormal variant, such as hemoglobin C.
For example, people with sickle-hemoglobin C HbSC disease have hemoglobin molecules with hemoglobin S and hemoglobin C instead of beta-globin. If mutations that produce hemoglobin S and beta thalassemia occur together, individuals have hemoglobin S-beta thalassemia HbSBetaThal disease. Abnormal versions of beta-globin can distort red blood cells into a sickle shape. The sickle-shaped red blood cells die prematurely, which can lead to anemia. Sometimes the inflexible, sickle-shaped cells get stuck in small blood vessels and can cause serious medical complications.
This condition is inherited in an autosomal recessive pattern , which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
Genetics Home Reference has merged with MedlinePlus. Learn more. The information on this site should not be used as a substitute for professional medical care or advice. Contact a health care provider if you have questions about your health. Sickle cell disease. From Genetics Home Reference.
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