Figure 2

Strategies for the identification of disease-causing variants in Mendelian diseases. Linkage or homozygosity mapping analysis can serve as the starting point in mutation identification by NGS. If linkage is conclusive (LOD score ≥3), linkage can be analyzed using a targeted re-sequencing approach. In cases of multiple suggestive linkage peaks (LOD score <3), whole exome/genome or candidate exome capture will be more suitable. Filtration and prioritization of variants can be customized depending on the availability of genetic information and NGS data. 1000G, 1,000 Genomes; dbSNP, Single Nucleotide Polymorphism database; EVS/EPS, Exome Variant Server (EVS) for the NHLBI Exome Sequencing Project (ESP); SIFT, sorting intolerant from tolerant.