Comparative genomic analysis of the clade B serpin cluster at human chromosome 18q21: amplification within the mouse squamous cell carcinoma antigen gene locus.
The human clade B serpins neutralize serine or cysteine proteinases and reside predominantly within the intracellular compartment. Genomic analysis shows that the 13 human clade B serpins map to either 6p25 (n = 3) or 18q21 (n = 10). Similarly, the mouse clade B serpins map to syntenic loci at 13A3.2 and 1D, respectively. The mouse clade B cluster at 13A3.2 shows a marked expansion in the number of serpin genes (n = 15). The purpose of this study was to determine whether a similar expansion occurred at 1D. Using STS-content mapping, comparative genomic DNA sequence analysis, and cDNA cloning, we found that the mouse clade B cluster at 1D showed nearly complete conservation of gene number, order, and orientation relative to those of 18q21. The only exception was the squamous cell carcinoma antigen (SCCA) locus. The human SCCA locus contains two genes, SERPINB3 (SCCA1) and SERPINB4 (SCCA2), whereas the mouse locus contains four serpins and three pseudogenes. Based on phylogenetic analysis and predicted amino acid sequences, amplification of the mouse SCCA locus occurred after rodents and primates diverged and was associated with some diversification of proteinase inhibitory activity relative to that of humans.
Askew
David J
DJ
Department of Pediatrics and the Division of Newborn Medicine, Harvard Medical School, Children's Hospital, 300 Longwood Avenue, Enders 9, Boston, MA 02115, USA.
Askew
Yuko S
YS
Kato
Yukari
Y
Turner
Russell F
RF
Dewar
Ken
K
Lehoczky
Jessica
J
Silverman
Gary A
GA
D000595:Amino Acid Sequence; D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics* / Q000378:metabolism; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics*; D003546:Cysteine Endopeptidases / Q000378:metabolism; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000235:genetics*; D010802:Phylogeny; D011480:Protease Inhibitors / Q000737:chemistry; D040641:Quantitative Trait Loci / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D012697:Serine Endopeptidases / Q000378:metabolism; D015843:Serpins / Q000235:genetics* / Q000378:metabolism
D000951:Antigens, Neoplasm; D011480:Protease Inhibitors; D015843:Serpins; C051072:squamous cell carcinoma-related antigen; C114880:trypsin-like serine protease; D012697:Serine Endopeptidases; D003546:Cysteine Endopeptidases