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| Open AccessRare variant contribution to human disease in 281,104 UK Biobank exomes
The authors analyse rare protein-coding genetic variants for association with 18,780 traits in the UK Biobank cohort.
- Quanli Wang
- , Ryan S. Dhindsa
- & Slavé Petrovski
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Perspective |
Improving reporting standards for polygenic scores in risk prediction studies
An updated set of reporting standards for the development, interpretation and evaluation of polygenic risk scores is presented, which should aid the translation of these scores into clinical applications.
- Hannah Wand
- , Samuel A. Lambert
- & Genevieve L. Wojcik
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Article |
Hepatic NADH reductive stress underlies common variation in metabolic traits
The authors identify an increased hepatic NADH/NAD+ ratio as an underlying metabolic parameter that is shaped by human genetic variation and contributes causally to key metabolic traits and diseases.
- Russell P. Goodman
- , Andrew L. Markhard
- & Vamsi K. Mootha
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Review Article |
A brief history of human disease genetics
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
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Article |
Correction of a pathogenic gene mutation in human embryos
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
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Article
| Open AccessAnalysis of protein-coding genetic variation in 60,706 humans
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
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Letter |
Large-scale discovery of novel genetic causes of developmental disorders
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
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Letter |
A common Greenlandic TBC1D4 variant confers muscle insulin resistance and type 2 diabetes
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
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Outlook |
Neuroscience: Dissecting appetite
A slew of new technologies are helping to map the neural circuits that control when, and how much, we eat.
- Bijal P. Trivedi
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Letter |
De novo mutations in histone-modifying genes in congenital heart disease
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
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News |
DNA donor rights affirmed
NIH committee urges that genome study subjects be told of medically relevant results.
- Erika Check Hayden
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News Feature |
Human genetics: Genomes on prescription
The first clinical uses of whole-genome sequencing show just how challenging it can be.
- Brendan Maher
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Letter |
Pronuclear transfer in human embryos to prevent transmission of mitochondrial DNA disease
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