Monoallelic expression of the protease inhibitor gene in humans, sheep, and cattle

Alpha 1-antitrypsin (AAT) deficiency is a genetic disorder that is associated with emphysema and liver disease because of mutations in the protease inhibitor (PI) gene. Although AAT deficiency is known to be an autosomal recessive disorder, some heterozygous individuals have been found to be affected. In this study, a polymorphism-based approach was used to study the expression status of the PI gene in humans, sheep, and cattle. RT-PCR products obtained from a total of 141 tissues were analyzed by direct sequencing and RFLP. Genomic DNA and cDNA from saliva from human individuals, including a family of four and two families of two, were sequenced. Thirteen individuals showed biallelic expression, and three individuals showed monoallelic expression. This differential expression of the PI gene might elucidate the puzzling heterozygote controversy in which heterozygotes have been found to be affected with AAT deficiency. Sheep and cattle tissues showed a complex pattern of expression. In most sheep tissues (17/25), PI transcripts were expressed from both parental alleles; in three tissues, PI transcripts were expressed preferentially from one allele and partially expressed from the other allele; in eight tissues, PI transcripts were monoallelically expressed. Comparisons of the expression patterns of cattle fetuses and their dams show that the PI gene is biallelically expressed in fetuses and predominantly monoallelically expressed in the dams. The expression analysis of the bovine PI transcripts in the different tissues demonstrated sporadic pattern of expression with preferential monoalleleic expression for some tissues and preferential biallelic expression for other tissues.