HOMOLOGOUS CHROMOSOMAL LOCATIONS OF THE 4 GENES FOR INTER-ALPHA-INHIBITOR AND PRE-ALPHA-INHIBITOR FAMILY IN HUMAN AND MOUSE - ASSIGNMENT OF THE ANCESTRAL GENE FOR THE LIPOCALIN SUPERFAMILY

The inter-α-inhibitor (IαI) and pre-α-inhibitor (PαI) family is composed of three plasma protease inhibitors, IαI, PαI, and bikunin, whose chains are encoded by a set of three evolutionarily related heavy (H) chain genes designated H1, H2, and H3 and a fourth gene, the so-called α1-microglobulin/bikunin precursor (AMBP) gene. The latter codes for a precursor that splits into: (i) α1-microglobulin, which belongs to the lipocalin superfamily; and (ii) bikunin, which is made up of two tandemly arranged protease inhibitor domains and belongs to the superfamily of Kunitz-type protease inhibitors. The bikunin chain is found in IαI and PαI molecules and it is also present as a free molecule in plasma. In human, the AMBP and H2 genes have been mapped to 9q32-q34 and 10p14-p15, respectively, while the H1 and H3 genes are tandemly located at 3p21.1-p21.2. In situ hybridization mappings indicate that the mouse AMBP gene (Intin-4) is located at 4C1 → C4, and the H1 (Intin-1) and H3 (Intin-3) genes are colocated at 14A2 → C1. In interspecific backcrosses (C57BL/6Pas × Mus spretus) a TaqI restriction variant in (and/or near) the H2 (Intin-2) gene identified a linkage of this gene with other polymorphic loci, which assigns Intin-2 to the centromeric area of chromosome 2. All such assignments are in conserved chromosomal regions between human and mouse. Therefore the genetic events that gave rise to the four IαI family genes took place prior to the divergence between human and mouse. Furthermore, our data confirm and extend conserved syntenies at HSA 3p and proximal MMU 14 and at HSA 10p and proximal MMU 2. They also indicate that the ancestral gene for the lipocalin-encoding genes arose at a chromosome area that has conserved syntenies at HSA 9q34 and MMU 4B → C. © 1992 Academic Press, Inc. All rights reserved.