Innate immunity genes as candidate genes: searching for relevant natural polymorphisms in databases and assessing family-based association of polymorphisms with human diseases

Abstract

The identification of genes underlying complex traits is a challenging task, and there are a limited number of confirmed genes that influence human complex diseases. In particular, few genes involved in complex diseases related to immune response, such as infectious diseases and inflammatory diseases, have been identified. Recent advances in genotyping technology lead to the depository of millions of single-nucleotide polymorphisms (SNPs) into public databases, and SNPs are considered powerful tools in the search for genes involved in complex diseases. A number of SNP-genotyping methods are available, and two critical points are to select the SNPs required for a comprehensive analysis and to perform association analyses that avoid statistical biases because of population substructure. This chapter describes a way to take advantage of the mass of known SNPs and to evaluate family-based association between polymorphisms and phenotypes related to diseases, with special emphasis on innate immunity genes. After summarizing relevant aspects of genetic epidemiology, I describe how to obtain SNP data from ENSEMBL visualize an annotated sequence containing SNPs with SNPper select SNPs on the basis of population frequency and functional information explore SNP data in the IIGA database focused on innate immunity genes evaluate the association of SNPs with quantitative phenotypes by using Quantitative trait Transmission/Disequilibrium Tests (QTDT) evaluate the association of SNPs with binary and quantitative phenotypes by using Family-Based Association Tests (FBAT). All the procedures use publicly available servers and free statistical programs for academic users.