Well curated human pedigrees like the iconic pedigrees maintained by the Centre d’Etude du Polymorphism Humain (CEPH) provide an invaluable resource for fundamental discoveries in human genetics and health. The CEPH collection includes families collected by R. White (Utah), J. Dausset (French), J. Gusella (Venezuelan), and J. Egeland (Amish). A significant and unique contribution from the University of Utah has been whole genome sequencing of the CEPH pedigrees, which has already produced two studies describing fundamental aspects of human genetics.
Quinlan, Jorde, and colleagues used these data to demonstrate that 10% of de novo human mutations are post-zygotic early embryonic events rather than inherited germline mutations, which has important implications for estimating disease risks in families. They also demonstrated that germline mutation rates vary substantially among families and that fathers contribute approximately ¾ of new single-gene mutations. The whole-genome pedigree data provided the first direct estimate of the rate at which mobile elements (“jumping genes”) insert into new locations in human genomes. These mobile elements constitute about half of the human genome and have significant effects on genetic variation and disease.
Large, three-generation human families reveal post-zygotic mosaicism and variability in germline mutation accumulation. Sasani TA, Pedersen BS, Gao Z, Baird L, Przeworski M, Jorde LB, Quinlan AR. Elife. 2019;8. pii: e46922.
Pedigree-based estimation of human mobile element retrotransposition rates. Feusier J, Watkins WS, Thomas J, Farrell A, Witherspoon DJ, Baird L, Ha H, Xing J, Jorde LB. Genome Res. 2019 Oct;29(10):1567 (cover article).
Press Releases and Media:
University of Utah Health: Genes Hop, Skip, and Jump to Alter the Human Genetic Code in About One In 20 Births.