AM Karinch and J Floros
Department of Cellular and Molecular Physiology, Pennsylvania State University, College of Medicine, Hershey 17033.

Human pulmonary surfactant protein A (SP-A) is encoded by two genes, SP- A1 and SP-A2. Reports from our laboratory and other investigations have shown heterogeneity in both genes within three regions (the 5' untranslated [5' UT], the coding, and the 3' untranslated [3' UT] regions). To more fully examine the variability in these regions and characterize the transcription start site in each gene, we used primer extension and 5' RACE to clone and then sequence cDNA clones from two individuals. These cDNAs extended from the transcription start site to approximately 40% of the 3' UT segment. The in vitro translatability of selected cDNAs was also tested. After analysis of our data, we found that: (1) the 5' UT of SP-A genes contains four (A, B, C, D for SP-A1) or three (A, B, D for SP-A2) untranslated exons, three of which (A, B, D) vary in length, and one of which (C) is new; (2) these exons are alternatively spliced and the major splice patterns as well as their relative frequency vary between the two genes (the major pattern for SP- A1 is AD'[81%] and the major patterns for SP-A2 are ABD [44%] and ABD'[49%]); (3) the SP-A1 gene uses three transcription start sites with equal frequency, whereas the SP-A2 gene uses only one; (4) splicing variability occurs among alleles and among individuals; (5) three previously undescribed alleles exist for the SP-A1 gene (6A2, 6A3, 6A4) and two for the SP-A2 gene (1A1, 1A2); and (6) a core group of 10 invariant nucleotides and four invariant amino acids can be used to discriminate between SP-A1 and SP-A2 alleles.

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