HUMAN SP-A - GENOTYPE AND SINGLE-STRAND CONFORMATION POLYMORPHISM ANALYSIS

We have previously characterized two surfactant protein A (SP-A) cDNAs termed 1A and 6A, as well as a 6A allelic variant termed 6A(1). These sequences are quite heterogeneous at the 3' untranslated region (3'UT). Differences between 6A and 6A(1) alleles include an 11-bp insertion/ deletion 407 bases downstream from the start of the translation termination codon and a base pair polymorphism (C or G) in exon 1 (position 1,193; White, Damm, Miller, Spratt, Schilling, Hawgood, Benson, and Cordell. Nature Lend. 317: 361-363, 1985). The 11-bp (GCCCACTGCCT) segment is present in 6A(1) and absent in 6A. The 6A/6A genotype, in a small number of specimens, showed a trend toward a higher frequency in the black Nigerian population compared with Caucasians. In this report, we examine the frequency of the 6A genotype in a larger number of samples from Caucasians and black Nigerians as well as the meiotic stability of the 3'UT heterogeneity. Slot-blot analysis and allele-specific oligonucleotide probes have confirmed that the 6A/6A genotype is more frequent in the Nigerian population. Single-strand conformation polymorphisms in the 3'UT appear to be stably inherited by members of a three-generation family, suggesting that these nucleotide variants represent natural polymorphisms in the population.