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

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".Pulmonary surfactant is a lipoprotein complex essential for normal lung function. Deficiency of surfactant or derangement of surfactant activity, may lead to respiratory distress syndrome (RDS) or congenital alveolar proteinosis (CAP) [1-3]. The pulmonary surfactant proteins, SP-A, SP-B, and SP-D play important roles in surfactant function, structure and metabolism. Genetic variants of SP-A and SP-B have been found to associate with RDS and the SP-B locus has been linked to the pathogenesis of CAP [2,4-8]. Therefore, study of differences among surfactant protein variants may help explain individual variability in susceptibility to pulmonary disease, and the genetic variants of surfactant proteins may serve as valuable markers for disease gene mapping.Linkage and association mapping are important tools for gene discovery. Both utilize available marker information to infer the location of disease susceptibility genes. They have been successfully used to map disease susceptibility genes such as Duchenne muscular dystrophy [9,10] and cystic fibrosis [11,12]. However, population stratification may confound linkage or association based mappi