Haplotype-aware detection of SERPINA1 variants by nanopore sequencing

Alpha-1 antitrypsin (AAT) is an acute-phase reactant with immunomodulatory properties that mainly inhibits neutrophilic elastase. Low serum levels cause AAT deficiency (AATD), an underdiagnosed condition that predisposes to pulmonary and hepatic diseases. SERPINA1 gene, which encodes AAT, contains more than 500 variants. PI*Z and PI*S alleles are the most diagnosed causes of AATD, but the role of SERPINA1 haplotypes in AAT function remains unknown. Nanopore sequencing may help to understand the relationship between SERPINA1 haplotypes and clinical phenotypes related to AATD, and others respiratory diseases. Therefore, it could become a valuable diagnostic tool for AATD in the future, since it allows deciphering the chromosomal configuration of rare variants when combined with PI*S and PI*Z alleles