Genotype

  • Article
    | Open Access

    Most genome-wide association studies assume an additive model, exclude the X chromosome, and use one reference panel. Here, the authors implement a strategy including non-additive models and find that the number of loci for age-related traits increases as compared to the additive model alone.

    • Marta Guindo-Martínez
    • , Ramon Amela
    •  & David Torrents
  • Article
    | Open Access

    Multiple algorithms exist for predicting heterogeneity and clonal architecture from the bulk sequencing of tumor tissue. Here, the authors report on an algorithm, FastClone, which was developed from a DREAM challenge and show that FastClone can accurately predict clonality in simulated data and data from colon cancer.

    • Yao Xiao
    • , Xueqing Wang
    •  & Yuanfang Guan
  • Article
    | Open Access

    Parallelized analysis in clinical genomics can lead to sample or data mislabelling, and could have serious downstream consequences. Here the authors present a tool to quantify sample genetic relatedness and detect such mistakes, and apply it to thousands of datasets from the ENCODE consortium.

    • Nauman Javed
    • , Yossi Farjoun
    •  & Noam Shoresh
  • Article
    | Open Access

    Multi-nucleotide variants (MNV) are genetic variants in close proximity of each other on the same haplotype whose functional impact is difficult to predict if they reside in the same codon. Here, Wang et al. use the gnomAD dataset to assemble a catalogue of MNVs and estimate their global mutation rate.

    • Qingbo Wang
    • , Emma Pierce-Hoffman
    •  & Daniel G. MacArthur
  • Article
    | Open Access

    Associations of copy number variations (CNVs) with complex traits are challenging to study because of their low frequency. Here, the authors analyse SNP array and array comparative genomic hybridization data of 100,028 individuals and report their associations with immune-related, cardiometabolic and neuropsychiatric diseases as well as cancer.

    • Yun Rose Li
    • , Joseph T. Glessner
    •  & Hakon Hakonarson
  • Article
    | Open Access

    Transposable elements (TE) make up a large component of the human genome and have been shown to contribute to human diseases. Here, Hormozdiari et al. estimate the contribution of TEs to the heritability of 41 complex traits and diseases and find enrichment of SINEs in blood traits.

    • Farhad Hormozdiari
    • , Bryce van de Geijn
    •  & Alkes L. Price
  • Article
    | Open Access

    An understanding of the genetic variants associated with medication use may shed light on the underlying biological pathways of disease, and aid in drug development. Here, Wu and colleagues conduct a GWAS for self-reported medication-use in the UK Biobank, finding more than 500 independent variants and many promising leads for future work.

    • Yeda Wu
    • , Enda M. Byrne
    •  & Naomi R. Wray
  • Article
    | Open Access

    Multimorbidities of common diseases often have shared underlying predisposing factors. Here Fadason et al. study the pleiotropy of SNPs and their effects on target genes by integrating chromatin interaction and expression quantitative trait loci data to identify target genes shared between phenotypes.

    • Tayaza Fadason
    • , William Schierding
    •  & Justin M. O’Sullivan
  • Article
    | Open Access

    Association between variants in 11 different genes and breast cancer risk has been established and sequencing of these genes is recommended to provide personalized diagnosis, therapy, and surveillance for the high-risk patients and their relatives. Here the authors analyse the frequency of germline pathogenic mutations in these genes specifically in a Japanese population.

    • Yukihide Momozawa
    • , Yusuke Iwasaki
    •  & Michiaki Kubo
  • Article
    | Open Access

    The majority of the human reference genome assembly is represented as a single consensus haplotype. Here, Wong et al. analyze de novo assemblies of 17 diverse, haplotype-resolved genomes to gain insights into the structure of genetic diversity and compile a list of alternative haplotypes across populations.

    • Karen H. Y. Wong
    • , Michal Levy-Sakin
    •  & Pui-Yan Kwok
  • Article
    | Open Access

    Male pattern baldness (MBP) is a complex trait that has genetic associations. Here, Pirastu and colleagues perform a genome-wide association study to show 71 susceptibility loci associated with MBP — 30 of which are novel — and that these loci can explain 38% of heritability.

    • Nicola Pirastu
    • , Peter K. Joshi
    •  & James F. Wilson
  • Article
    | Open Access

    Systemic dissection of sexually dimorphic phenotypes in mice is lacking. Here, Karp and the International Mouse Phenotype Consortium show that approximately 10% of qualitative traits and 56% of quantitative traits in mice as measured in laboratory setting are sexually dimorphic.

    • Natasha A. Karp
    • , Jeremy Mason
    •  & Jacqueline K. White
  • Article
    | Open Access

    Imputation uses genotype information from SNP arrays to infer the genotypes of missing markers. Here, the authors show that an imputation reference panel derived from whole-genome sequencing of 3,781 samples from the UK10K project improves the imputation accuracy and coverage of low frequency variants compared to existing methods.

    • Jie Huang
    • , Bryan Howie
    •  & Nicole Soranzo
  • Article |

    Yin–yang haplotypes are stretches of DNA that differ at multiple markers and exhibit two disparate forms. Here, the authors identify a pair of 284-nucleotide-long yin–yang haplotypes that encompass the gephyringene, and show that these human-specific haplotypes evolved rapidly and bear functional implications.

    • Sharlee Climer
    • , Alan R. Templeton
    •  & Weixiong Zhang
  • Article
    | Open Access

    The genetic make-up of people living in the Americas has been shaped heavily by migration. Here the authors use a haplotype-based approach to reconstruct American genomic ancestry using genotype data from 2,500 individuals, revealing a previously unrecognized genetic contribution from European and African populations.

    • Francesco Montinaro
    • , George B.J. Busby
    •  & Cristian Capelli
  • Article
    | Open Access

    Diet variations can alter gut microbial composition, but the potential influence of host genetic factors on these effects is unclear. Here, the authors show, in humans and in natural and laboratory fish populations, that such effects are dependent on the host’s sex, a genetically determined factor.

    • Daniel I. Bolnick
    • , Lisa K. Snowberg
    •  & Richard Svanbäck
  • Article |

    Here, Brotherton and colleagues sequence 39 mitochondrial genomes from ancient human remains. They track population changes across Central Europe and find that the foundations of the European mitochondrial DNA pool were formed during the Neolithic rather than the post-glacial period.

    • Paul Brotherton
    • , Wolfgang Haak
    •  & Janet S. Ziegle
  • Article
    | Open Access

    Progressive sensorineural hearing loss affects many people, but the underlying genetics remain largely undefined. Here, the authors identify mutations inGIPC3in mice and two consanguineous families that lead to hearing loss and in mice cause defects in the structure of stereocilia bundles and audiogenic seizures.

    • Nikoletta Charizopoulou
    • , Andrea Lelli
    •  & Konrad Noben-Trauth