Chris Mason describes how he used the Illumina Genome Network (IGN) for low input, whole-genome sequencing of rare clinical cases with extreme phenotypes from the NIH's Undiagnosed Disease Program (UDP) and a consanguineous family with neural-tube defects (NTDs). For all sequenced samples, the IGN data provided high coverage across the genome, including regulatory regions like promoters and enhancers, allowing the research team to pinpoint likely genes for the disease phenotypes. A comparison of output data from IGN software suite (CASAVA/GROUPER) to SAMtools/GATK revealed a high overlap of SNVs and indels between software platforms. The variants specific to each software suite showed higher Ti/Tv ratio. Overall, the results highlight the ease and speed of whole-genome sequencing services for identifying disease phenotypes. The genetic data can be combined with other biological modalities (transcriptional, epigenetic, proteomic) to function as a systems biology approach for personalized medicine.