However, the genetic control of most biological traits is usually not this simple. HBCGM cannot evaluate complex genetic traits that are affected by multiple alleles located in discrete regions of the genome, but can evaluate phenotypic traits that are predominantly regulated by allelic differences within a contiguous genomic region. These allelic differences can produce a spectrum of phenotypes that can match the haplotype structure within a region. In these situations, HBCGM is better able than a GWAS to analyze phenotypes with multiple different states (Figure 2). For example, the composite effect of alleles at 2 SNPs contributed to three discrete levels of H2-Eα gene expression in an inbred strain panel. HBCGM produced a block with three distinct haplotypes, which maximized detection power for analyzing this gene expression difference [7]. Since GWAS methodology can analyze only one SNP at a time, it cannot distinguish the three groups with distinct gene expression levels.
