Inherited diseases cystic fibrosis

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). 

The regulation of epithelial Cl -channels has been examined in many laboratories, and these studies have been intensified with the recognition that the Cl -channel regulation in epithelia is defective in a very common and clinically serious inherited disease, namely cystic fibrosis [17,18]. Efforts in this direction have not yet arrived at coherent concepts, and many published models [19-22] may have to be modified or revised. 

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. 

Racial and ethnic groups may also vary in the extent to which they are carriers of autosomal recessive or dominant diseases that could be inherited by offspring. African Americans will be subject to many of the same diseases as whites, for example, cystic fibrosis, but the incidence of the disease may vary. In some cases, however, the incidence of disease may be higher among African Americans, just as it is for some white subgroups, for example, the higher incidence of Tay-Sachs disease and BRCA1 and -2 mutations in Ashkenazi Jews. 

Cystic fibrosis (CF) is the most common potentially lethal autosomal recessive disease among Caucasians. The incidence is estimated to be approximately 1 in 2000 births (Bl). Since it is inherited as an autosomal recessive condition, screening to identify couples at risk has been suggested. However, CF screening is complicated because many mutations of the CF gene exist. Thus, the feasibility of screening a population for carriers of cystic fibrosis gene mutations is primarily dependent upon the frequency of the common mutation in that population. 

Genetic alterations or abnormalities of germ cells, some of which can be caused by toxicant exposure, can be manifested by adverse effects on progeny. The important health effects of these kinds of alterations may be appreciated by considering the kinds of human maladies that are caused by inherited recessive mutations. One such disease is cystic fibrosis, in which the clinical phenotype has thick, dry mucus in the tubes of the respiratory system such that inhaled bacterial and fungal spores cannot be cleared from the system. This results in frequent, severe infections. It is the consequence of a faulty chloride transporter membrane protein that does not properly transport Cl ion from inside cells to the outside, where they normally retain water characteristic of healthy mucus. The faulty transporter protein is the result of a change of a single amino acid in the protein. 

Genetic maps have been used successfully to find the single gene responsible for rare inherited diseases such as cystic fibrosis and muscular dystrophy. Maps are now being used by scientists to... 

Single-gene (also called Mendefian) disorders number more than 6000, with an incidence of about 1 in 200 births. Some examples include cystic fibrosis, sickle ceU anaemia, Marfan syndrome, Huntington s disease and hereditary haemochromatosis. Single-gene disorders are inherited in recognisable patterns autosomal dominant, autosomal recessive and X-hnked. 

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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