ISB sequenced the genomes of a family in which the two children had the disorder but not the parents and reported results in Science.
The Institute for Systems Biology (ISB) employed Complete Genomics’ human genome sequencing service to sequence a family quartet to verify the gene responsible for Miller syndrome and to estimate the intergenerational mutation rate. The researchers also aimed to determine the depth of genetic information possible in analyzing a full family’s sequence.
The study titled “Analysis of Genetic Inheritance in a Family Quartet by Whole Genome Sequencing” will be published in Science. The four-member family that was analyzed comprised two children who had Miller syndrome and ciliary dyskinesia, a lung disorder similar to cystic fibrosis, but neither parent was affected.
Complete Genomics sequenced the four genomes to a depth of 51x to 88x, and 85–92% of the bases in each genome were called. A comparative analysis of the four genomes yielded four genes consistent with recessive inheritance of rare variations. One of these genes called DHODH was concurrently identified as a cause of Miller syndrome and reported in Nature Genetics in January. Mutations in a second gene, DNAH5, were previously shown to cause primary ciliary dyskinesia.
“We are convinced that this new kind of analysis, family sequencing, will be a remarkably powerful scientific and medical tool in the future,” says David Galas, professor and svp of ISB.