Medical genetics

  • Review Article |

    This Review describes progress in the study of human genetics, in which rapid advances in technology, foundational genomic resources and analytical tools have contributed to the understanding of the mechanisms responsible for many rare and common diseases and to preventative and therapeutic strategies for many of these conditions.

    • Melina Claussnitzer
    • , Judy H. Cho
    •  & Mark I. McCarthy
  • Article |

    CRISPR–Cas9 genome editing is used to induce a DNA repair response and correct a disease-causing heterozygous mutation in human embryos with reduced mosaicism and preferential repair using the wild-type copy of the gene.

    • Hong Ma
    • , Nuria Marti-Gutierrez
    •  & Shoukhrat Mitalipov
  • Article
    | Open Access

    Exome sequencing data from 60,706 people of diverse geographic ancestry is presented, providing insight into genetic variation across populations, and illuminating the relationship between DNA variants and human disease.

    • Monkol Lek
    • , Konrad J. Karczewski
    •  & Daniel G. MacArthur
  • Letter |

    Up to half of children with severe developmental disorders of probable genetic origin remain without a genetic diagnosis; here, in a systematic and nationwide study of 1,133 children with severe, undiagnosed developmental disorders, and their parents, exome sequencing and array-based detection of chromosomal rearrangements reveals novel genes causing developmental disorders, increasing the proportion of children that can now be diagnosed to 31%.

    • T. W. Fitzgerald
    • , S. S. Gerety
    •  & M. E. Hurles
  • Letter |

    An association mapping study of type-2-diabetes-related quantitative traits in the Greenlandic population identified a common variant in TBC1D4 that increases plasma glucose levels and serum insulin levels after an oral glucose load and type 2 diabetes risk, with effect sizes several times larger than any previous findings of large-scale genome-wide association studies for these traits.

    • Ida Moltke
    • , Niels Grarup
    •  & Torben Hansen
  • Letter |

    Exome sequencing of patients with congenital heart disease (CHD) and their unaffected parents reveals an excess of strong-effect, protein-altering de novo mutations in genes expressed in the developing heart, many of which regulate chromatin modification in key developmental genes; collectively, these mutations are predicted to account for approximately 10% of severe CHD cases.

    • Samir Zaidi
    • , Murim Choi
    •  & Richard P. Lifton
  • Letter |

    Mutations in mitochondrial DNA (mtDNA) are a common cause of human genetic disease. It has been shown in non-human primates that nuclear transfer techniques might be an approach to prevent the transmission of mtDNA mutations. The proof of principle has now been extended to human embryos. Pronuclei were transferred between human zygotes, which developed onwards to the blastocyst stage in vitro. Carry-over of mtDNA from the donor zygotes to the recipients was minimal.

    • Lyndsey Craven
    • , Helen A. Tuppen
    •  & Douglass M. Turnbull