Human SP-A locus: allele frequencies and linkage disequilibrium between the two surfactant protein A genes.

Abstract

Two surfactant protein A (SP-A) genes and several alleles for each SP-A locus have been previously described. In this report we investigate the potential usefulness of the SP-A loci as markers for genetic studies. We establish conditions that allow the identification of alleles with very similar sequences; We also determine the degree of polymorphism for each SP-A locus: The heterozygosity and polymorphism information content (PIC) values for the SP-A1 locus are 0.63 and 0.55, respectively, and for the SP-A2 locus are 0.50 and 0.56. In the course of these studies, we identify one new SP-A2 allele and show that the SP-A1 and SP-A2 loci are in linkage disequilibrium (P < 0.000001). We also identify 19 of the 20 possible haplotypes in a population of n = 239. Nine of the observed haplotypes reach statistical significance (P < 0.01) in this population, and the segregation of two haplotypes (6A2/1A0 and 6A4/1A) without recombination is verified in a family pedigree. These data together indicate that both SP-A loci are sufficiently polymorphic to be good markers for use in genetic studies. Furthermore, the finding of one novel allele suggests that additional unknown SP-A alleles are yet to be found.

Glucocorticoid inhibition of human SP-A1 promoter activity in NCI-H441 cells

“…4-fold upon removal of k227\k31 (which contains the three aforementioned cis-acting elements) from the SP-A1 promoter (Figure 3). The reduction of SP-A1 promoter activity upon removal of k227\k31 is similar to that seen when either the CRE SP-A site [24] or the GT box [29] is removed from the SP-A2 promoter. In the functional analysis of the SP-A2 CRE SP-A site and GT box, primary cultures of human alveolar type-II cells were infected with adenoviral human growth hormone reporter constructs, whereas in the present study NCI-H441 cells and CAT reporter constructs were used.…”

“…The 416\255 PCR product from the NCI-H441 cell line represents the 6A% allele [23,24]. At the present time we do not have a comparable SP-A2-specific primer pair (i.e.…”

“…that could be used to specifically amplify much of the 5h-flanking region from genomic DNA). Therefore, in order to generate a CAT reporter construct that contained the SP-A2 promoter, DNA isolated from PAC (P1 artificial chromosome) 307-L19 [9], which contains the SP-A2 1A" allele [23,24], was used as template in PCR.…”

Regulation of translation by upstream translation initiation codons of surfactant protein A1 splice variants

“…The SP-A1 and SP-A2 gene-specific products are distinguished by four amino acid differences within the collagen-like region of the molecules. To add to the complexity of SP-A genetic variability, several different 5=-untranslated region (UTR) splice variants have been reported (15,36). These result from alternative splicing of a number of different untranslated exons in the 5=-UTR (A, A=, AЉ, B, B=, C, C=, D, D=) (36,55,76) and have been shown to differentially affect SP-A regulation (89,90).…”

Characterization of a human surfactant protein A1 (SP-A1) gene-specific antibody; SP-A1 content variation among individuals of varying age and pulmonary health

“…alveolar proteinosis; bronchoalveolar lavage fluid; cystic fibrosis; peptide antibody; surfactant protein A HUMAN SURFACTANT PROTEIN A (SP-A), a member of the C-type lectin or collectin family, is encoded by two functional genes, SP-A1 and SP-A2, with a high percentage of sequence similarity detected at the nucleotide (94%) and the amino acid (aa) (96%) levels. More than 30 alleles have been characterized for these two genes, with four SP-A1 alleles (6A, 6A 2 , 6A 3 , and 6A 4 ) and six SP-A2 alleles (1A, 1A 0 , 1A 1 , 1A 2 , 1A 3 , and 1A 5 ) most frequently observed in the general population (10,14,16,40,67). Although a high level of sequence similarity is shared among the SP-A genes and their corresponding alleles, in vitro studies have identified both qualitative (22,36,57,60,77,80,81) and quantitative (24,35,38,46,56,69,70,78,79) differences between the two genes.…”