Figure 2

Identification of genetic variation underlying human disease using linkage analysis and genome-wide association studies. (a) Rare Mendelian traits, such as a monogenic disease with autosomal dominance inheritance, can be studied using linkage analysis in a family. The disease status is followed within a pedigree (seven affected individuals depicted in red). (b) The disease loci (red bar) co-segregates with the genetic marker (blue bar), located 10 centimorgans (cM) apart. Each of the seven individuals with the disease carries the blue genetic marker, both inherited from the affected 'parent' chromosome (yellow). (c) Genetic variants underlying common diseases can be statistically identified by using SNP-based linkage disequilibrium (LD) maps. The frequency of a causative variant (red diamond) will be higher (62%) among those with the disease when compared with a control population (50%). (d) LD map of 11 variants cluster into three blocks of correlation r² > 0.8 (red scale correlation matrix). The LD between polymorphisms needs to be empirically determined by genotyping a population and calculating the correlation.