A 370-kb Cosmid Contig of the Serpin Gene Cluster on Human Chromosome 14q32.1: Molecular Linkage of the Genes Encoding α1-Antichymotrypsin, Protein C Inhibitor, Kallistatin, α1-Antitrypsin, and Corticosteroid-Binding Globulin

Abstract

The human genes encoding α1-antitrypsin (α1AT, gene symbol PI), corticosteroid-binding globulin (CBG), α1-antichymotrypsin (AACT), and protein C inhibitor (PCI) are related by descent, and they all map to human chromosome 14q32.1. This serine protease inhibitor (serpin) gene cluster also contains an antitrypsin-related sequence (ATR, gene symbol PIL), but the precise molecular organization of this region has not been defined. In this report we describe the generation and characterization of an ∼370-kb cosmid contig that includes all five serpin genes. Moreover, a newly described serpin, kallistatin (KAL, gene symbol PI4), was also mapped within the region. Gene order within this interval is cen–CBG–ATR–α1AT–KAL–PCI–AACT–tel. The genes occupy ∼320 kb of genomic DNA, and they are organized into two discrete subclusters of three genes each that are separated by ∼170 kb. The distal subcluster includes KAL, PCI, and AACT; it occupies ∼63 kb of DNA, and all three genes are transcribed in a proximal-to-distal orientation. Within the subcluster, there is ∼12 kb of intergenic DNA between KAL and PCI and ∼19 kb between PCI and AACT. The proximal subcluster includes α1AT, ATR, and CBG; it occupies ∼90 kb of genomic DNA, with ∼12 kb of DNA between α1AT and ATR and ∼40 kb between ATR and CBG. These genes are all transcribed in a distal-to-proximal orientation. This represents the first detailed physical map of the serpin gene cluster on 14q32.1.