Whole genome sequencing of entire family beneficial

The Institute for Systems Biology (ISB) has analyzed the first whole genome sequences of a human family of four. The findings of a project funded through a partnership between ISB and the University of Luxembourg was published online today by Science on its Science Express website. It demonstrates the benefit of sequencing entire families, including lowering error rates, identifying rare genetic variants and identifying disease-linked genes.

“Our study illustrates the beginning of a new era in which the analysis of a family’s genome can aid in the diagnosis and treatment of individual family members. We could soon find that our family’s genome sequence will become a normal part of our medical records.”

“We were very pleased and a little surprised at how much additional information can come from examining the full genomes of the same family.” said David Galas, PhD, a corresponding author on the paper, an ISB faculty member and its senior vice president of strategic partnerships. “Comparing the sequences of unrelated individuals is useful, but for a family the results are more accurate. We can now see all the genetic variations, including rare ones, and can construct the inheritance of every piece of the chromosomes, which is critical to understanding the traits important to health and disease.”

“The continuing decline in the difficulty and cost of sequencing now enables us to use these new strategies for deriving genetic information that was too difficult or expensive to access in the past,” Galas said.

ISB partnered with Complete Genomics, based in Mountain View California, to sequence the genomes of a father, mother and two children. Both children had two recessive genetic disorders, Miller syndrome, a rare craniofacial disorder, and primary ciliary dyskinesia (PCD), a lung disease. By sequencing the entire family, including the parents, researchers were able to reduce the number of candidate genes associated with Miller syndrome to four.

“An important finding is that by determining the genome sequences of an entire family one can identify many DNA sequencing errors, and thus greatly increase the accuracy of the data,” said Leroy Hood, MD, PhD, the paper’s other corresponding author, and co-founder and president of ISB. "This will ultimately help us understand the role of genetic variations in the diagnosis, treatment, and prevention of disease."

An exciting finding from this study, the first direct estimate of human intergenerational mutation rate, is how much the genome changes from one human generation to the next – the intergenerational mutation rate. The researchers found that gene mutations from parent to child occurred at half the most widely expected rate.

“This estimate could have implications for how we think about genetic diversity, but more importantly the approach has the potential to increase enormously the power and impact of genetic research,” said Galas. “Our study illustrates the beginning of a new era in which the analysis of a family’s genome can aid in the diagnosis and treatment of individual family members. We could soon find that our family’s genome sequence will become a normal part of our medical records.”