The human serum amyloid A protein (SAA) superfamily gene cluster: mapping to chromosome 11p15.1 by physical and genetic linkage analysis

Abstract

The human serum amyloid A protein (SAA) family comprises a number of small, hepatically produced, differentially expressed apolipoproteins encoded by genes localized on the short arm of chromosome 11.SAA1 and SAA2 are highly related genes that together encode the acute-phase SAAs; SAA3 is a pseudogene; and SAA4 is a low-level constitutively expressed gene encoding constitutive SAA. We have used a combination of physical and genetic mapping techniques to provide evidence that the SAA gene superfamily comprises a cluster of closely linked genes localized to 11p15.1. Pulsed-field gel electrophoresis placed SAA1 to within 350 kb of the previously linked SAA2 and SAA4 genes. SAA locus-specific polymerase chain reaction amplification from a panel of somatic cell hybrids carrying defined regions of chromosome 11p mapped all four loci to 11p15.1-pter. Fluorescence in situ hybridization analysis using a cosmid probe carrying the SAA2 and SAA4 genes refined the localization of these genes (and SAA1) to 11p15.1. To order SAA3 on the genetic map, a highly polymorphic (CA)n dinucleotide repeat within SAA3 was typed through the CEPH reference families. In accordance with the physical localization of SAAs 1, 2, and 4, SAA3 maps to the 11p15.1 region proximal to the parathyroid hormone (PTH) locus (theta = 0.02; lod = 12.020) and distal to D11S455 (theta = 0.058, lod = 8.274). To provide further evidence of an SAA superfamily gene cluster, an NcoI restriction fragment length polymorphism in the SAA2 gene was also typed through the CEPH reference panel.(ABSTRACT TRUNCATED AT 250 WORDS)