Sickle cell disease detection

Restriction analysis can be used to detect sickle cell disease prenatally, since the DNA of all cells, including amniotic cells, carries the mutant DNA. It is much more difficult to obtain fetal blood for the analysis of the mutant hemoglobin A P-chain. Furthermore, fetal blood is composed mostly of fetal hemoglobin, sinee-hemoglobin A is made later in development. 

Carrier Detection and Prenatal Diagnosis of Sickle Cell Disease... 

DNA probes are now used routinely to detect the presence of mutant alleles in fetal cells obtained by amniocentesis, as well as in cells removed from affected adults or carriers. Many inherited disorders, such as sickle cell disease, cystic fibrosis, Huntington s disease, Duchenne s muscular dystrophy, and dozens of other Mendelian (single-gene) disorders, can now be diagnosed in fetuses and adults. In addition to inherited disorders, DNA probes are used to detect the presence of active oncogenes or inactive tumor suppressor genes in cancerous tissues removed from patients (Chapter 26). 

Health (NIH) Counseling Development Conference. Clinical practice includes several hundred genetic tests that are able to detect mutations such as those associated with breast and colon cancers, muscular dystrophy, cystic fibrosis, sickle-cell disease, and Huntington s disease. 

The detection of restriction fi agment length polymorphisms (RFLPs) facilitates prenatal detection of hereditary disorders such as sickle cell trait, beta-thalassemia, infant phenylketonuria, and Huntington s disease. Detection of RFLPs involves cleavage of double-stranded DNA by restriction endonucleases, which can detect subtle alterations in DNA that affect their recognized sites. Chapter 40 provides further details concerning the use of PCR and restriction enzymes for diagnosis. 

RFLPs are often a reflection of individual genetic diversity and are not related to a clinical phenotype, but occasionally they can be diagnostic of an inherited disease. This technique is relatively new yet, it has been applied to the prenatal detection of sickle cell anemia, thalassemia, phenylketonuria, a,-antitrypsin deficiency, Huntington s chorea, Duchenne muscular dystrophy, hemophilia A and B, cystic fibrosis, and several other, diseases. 

ASO probes used to detect the sickle cell mutation and differentiate between sickle cell trait and disease. 

Among its many other applications, DNA fingerprinting is widely used for the diagnosis of genetic disorders. Cystic fibrosis, hemophilia, Huntington s disease, Tay-Sachs disease, and sickle-cell anemia are among the many diseases that can be detected, enabling early treatment of an affected child. In addition, the U.S. Department of Defense now requires blood and saliva samples from all military personnel. The samples are stored, and DNA is extracted should the need for identification of a casualty arise. 

Genetic screening had reached a new stage in late 1960 when public health officials initiated voluntary screening of adults to detect heterozygous carriers of specific recessive traits, such as Tay-Sachs, another degenerative disease. Subsequently, several states passed laws to establish mandatory programs to screen for carriers of sickle-cell anemia. 

Rarely, the nucleotide sequence change responsible for a disease mutation alters the recognition sequence for a restriction enzyme, enabling the disease gene to be detected simply by the creation or abolition of a restriction endonuclease site. The classic example of direct detection is sickle cell anemia (Fig. 5) an A to T... 

Southern blotting can be used to follow the inheritance of selected genes. Mutations within restriction sites change the sizes of restriction Ifagments and hence the positions of bands in Southern-blot analyses. The existence of genetic diversity in a population is termed polymorphism. The detected mutation may itself cause disease or it may be closely linked to one that does. Genetic diseases such as sickle-cell anemia, cystic fibrosis, and Huntington chorea can be detected by RFLP analyses. 

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