A mutant gene for α1-antitrypsin (αlAT) was isolated and analyzed to determine a method for molecular diagnosis of the protein deficiency, which is involved in severe liver and lung diseases. The mutant gene (called Z allele) has two point mutations: the first mutation is located in exon V and is present in all the subjects with protein deficiency; the other one is located in exon III and is present in the same subjects and in 23% ot normal individuals. To identity exon III and exon V ot α1AT among the total genome we synthesized lour oligonucleotides that are complementary to sequences flanking the mutation sites and act as primers for a polymerization chain reaction. The amplified fragments were digested with BstEII enzyme. The restriction site is present in exon III ot the normal gene and is abolished by the mutation in exon III of the Z gene. The amplified DNA fragments were cloned and sequenced. These results allow: a) a molecular diagnosis of the mutation (even in at risk fetuses); b) the construction of mutant genes tor production or transgenic mice.
|Translated title of the contribution||Human αl-antitrypsin: molecular diagnosis of mutation and animal models of human pathology.|
|Number of pages||6|
|Publication status||Published - Mar 1990|
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