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This Week in PNAS: Nov 1, 2016

In the early, online edition of the Proceedings of the National Academy of Sciences, the Chinese University of Hong Kong's Dennis Lo and colleagues consider the performance of "second generation" non-invasive fetal genome analyses, done using deep haploid sequencing of maternal plasma DNA to better detect de novo mutations in the fetus. By combining new bioinformatic filtering strategies with genome depths of 195-fold to 270-fold coverage, on average, the team reports that it was able to detect de novo fetal mutations with up to 85 percent sensitivity and a 74 percent positive predictive value in third trimester cases. It presented a proof-of-principle analysis of a second trimester pregnancy involving a fetus with cardiofaciocutaneous syndrome that had a de novo BRAF mutation.

An international team led by investigators in France presents a multigenerational marine fish pedigree that it put together using genotyping data collected from fish near Papua New Guinea's Kimbe Island during the course of a decade. With microsatellite markers in DNA isolated from thousands of fin clip samples, the researchers retraced relationships for more than 2,900 orange clownfish (Amphiprion percula) from 121 fish families over five generations, stemming from 502 known founder fish. "Resolving multigenerational pedigrees during a relatively short period, as we present here, provides a framework for assessing the ability of marine populations to persist and adapt to accelerating climate change," they note.

Finally, researchers from Washington State University, the University of Illinois at Urbana-Champaign, and TransOva-ViaGen report on a strategy for applying gene editing to develop cattle lines that are resistant to forms of pneumonia caused by Mannheimia haemolytica. Using a zinc finger nuclease-based gene editing approach, the team targeted sequence coding for the signal peptide CD18 that's normally expressed on the surface of white blood cells and targeted by a M. haemolytica leukotoxin. After modifying the CD18 sequence in a primary fibroblast line developed from a male Holstein fetus, the group used these edited fibroblasts for somatic nuclear transfer, producing a cloned fetus with M.haemolytica leukotoxin-resistant white blood cells.