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SP-A, SP-B, and SP-D are pulmonary surfactant proteins. Several linkage and association studies have been done using these genes as markers to locate pulmonary disease susceptibility genes, but few have studied the markers systematically in different ethnic groups. Here we studied eight markers in SP-A, SP-B, and SP-D genes in seven ethnic groups from three races (Caucasian, Black and Hispanic). We measured the similarity of the marker distribution among the ethnic groups in order to see whether people in different ethnic groups or races could be mixed together for linkage and association studies. To evaluate the usefulness of these markers, we estimated the informativeness of each marker loci in the seven ethnic groups by assessing their heterozygosity and PIC values. We also conducted linkage disequilibrium (LD) analysis to identify associated marker loci and to estimate the haplotype frequencies in each of the seven ethnic groups in an attempt to find valuable haplotypes so that the level of polymorphism of the "markers" could be increased.Our findings indicate that allele and genotype frequencies may be different between different ethnic groups, especially between ethnic groups from different races. The markers are in general polymorphic in a variety of study groups, especially for the two SP-A1 and SP-A2 markers. Two-locus LD analysis reveals that three pairs of loci are strongly associated together: B-18(A/C) with B1013(A/C), DA11(C/T) with DA160(A/G), SP-A1 with SP-A2. Three-locus LD analysis suggests that B-18(A/C), B1013(A/C) and B1580(C/T) are strongly associated with each other.Allele and genotype frequency differences imply that different ethnic groups should be mixed with extreme caution before performing linkage and association studies. The associated markers could be used together to increase the level of polymorphism and the informativeness of the "markers".

Study of human SP-A, SP-B and SP-D loci: allele frequencies, linkage disequilibrium and heterozygosity in different races and ethnic groups.