South Asia's multiple founder populations

Latest Research

  • Article |

    Loss of BAF47 destabilizes the BAF complex on chromatin, and reintroduction of BAF47 leads to enhancer activation and Polycomb opposition at bivalent promoters. BAF47 loss affects BAF and PBAF complexes, which have distinct functions in regulation of enhancers and promoters.

    • Robert T Nakayama
    • , John L Pulice
    • , Alfredo M Valencia
    • , Matthew J McBride
    • , Zachary M McKenzie
    • , Mark A Gillespie
    • , Wai Lim Ku
    • , Mingxiang Teng
    • , Kairong Cui
    • , Robert T Williams
    • , Seth H Cassel
    • , He Qing
    • , Christian J Widmer
    • , George D Demetri
    • , Rafael A Irizarry
    • , Keji Zhao
    • , Jeffrey A Ranish
    •  & Cigall Kadoch
  • Technical Report |

    Graphtyper is a fast and scalable method for variant genotyping that aligns short-read sequence data to a pangenome. Graphtyper was able to accurately genotype 90 million sequence variants in the whole genomes of 28,000 Icelanders, including those in six HLA genes.

    • Hannes P Eggertsson
    • , Hakon Jonsson
    • , Snaedis Kristmundsdottir
    • , Eirikur Hjartarson
    • , Birte Kehr
    • , Gisli Masson
    • , Florian Zink
    • , Kristjan E Hjorleifsson
    • , Aslaug Jonasdottir
    • , Adalbjorg Jonasdottir
    • , Ingileif Jonsdottir
    • , Daniel F Gudbjartsson
    • , Pall Melsted
    • , Kari Stefansson
    •  & Bjarni V Halldorsson
  • Article |

    Lineage-tracing experiments in the mouse show that Lgr6, but not Lgr5, functions as a cancer stem marker in skin squamous cell carcinomas (SCCs). The authors also show that Lgr6-knockout mice are predisposed to SCC development, through a mechanism that includes compensatory upregulation of Lgr5.

    • Phillips Y Huang
    • , Eve Kandyba
    • , Arnaud Jabouille
    • , Jonas Sjolund
    • , Atul Kumar
    • , Kyle Halliwill
    • , Melissa McCreery
    • , Reyno DelRosario
    • , Hio Chung Kang
    • , Christine E Wong
    • , Jost Seibler
    • , Vincent Beuger
    • , Maurizio Pellegrino
    • , Adam Sciambi
    • , Dennis J Eastburn
    •  & Allan Balmain
  • Article |

    High-resolution contact maps of active enhancers and target genes generated by H3K27ac HiChIP in primary human cells provide rational guides to link noncoding disease-associated risk variants to candidate causal genes. Genes are validated by CRISPR activation and interference at connected enhancers and eQTL analysis, leading to a fourfold increase in the number of potential target genes for autoimmune and cardiovascular diseases.

    • Maxwell R Mumbach
    • , Ansuman T Satpathy
    • , Evan A Boyle
    • , Chao Dai
    • , Benjamin G Gowen
    • , Seung Woo Cho
    • , Michelle L Nguyen
    • , Adam J Rubin
    • , Jeffrey M Granja
    • , Katelynn R Kazane
    • , Yuning Wei
    • , Trieu Nguyen
    • , Peyton G Greenside
    • , M Ryan Corces
    • , Josh Tycko
    • , Dimitre R Simeonov
    • , Nabeela Suliman
    • , Rui Li
    • , Jin Xu
    • , Ryan A Flynn
    • , Anshul Kundaje
    • , Paul A Khavari
    • , Alexander Marson
    • , Jacob E Corn
    • , Thomas Quertermous
    • , William J Greenleaf
    •  & Howard Y Chang
  • Letter |

    Missense mutations affecting lysine 91 in the histone H4 core cause a developmental syndrome marked by growth delay, microcephaly and intellectual disability. These mutations cause genomic instability by interfering with H4K91 ubiquitination, leading to abnormal cell cycle progression and apoptosis during early development.

    • Federico Tessadori
    • , Jacques C Giltay
    • , Jane A Hurst
    • , Maarten P Massink
    • , Karen Duran
    • , Harmjan R Vos
    • , Robert M van Es
    • , Deciphering Developmental Disorders Study
    • , Richard H Scott
    • , Koen L I van Gassen
    • , Jeroen Bakkers
    •  & Gijs van Haaften
  • Article |

    Melissa Gymrek and colleagues estimate mutation parameters for each short tandem repeat (STR) in the human genome. They find that local sequence features impact these estimates and they create a framework for measuring constraint at STRs by comparing observed and expected mutation rates, providing a tool for prioritizing pathogenic variants.

    • Melissa Gymrek
    • , Thomas Willems
    • , David Reich
    •  & Yaniv Erlich

News & Comment

  • Editorial |

    A solution to screening for recessive heritable disorders and identifying genetic influences on common diseases is to be found in the history of one of the world's most populous regions. Large South Asian populations are a mosaic of smaller populations, many of which have founder effects as extreme as those in the European isolates that first inspired genetic medicine.

  • News and Views |

    Genetic and functional analyses of 120 mouse strains have identified a heart regeneration candidate gene that modulates the contractile sarcomeric apparatus. This gene, Tnni3k, controls the frequency of the mononuclear, diploid cardiomyocyte population, which affects cardiomyocyte proliferative potential after injury.

    • Ana Vujic
    • , Vinícius Bassaneze
    •  & Richard T Lee
  • News and Views |

    ERG overexpression in prostate cancers promotes the development of widespread changes in gene expression and chromatin landscapes, leading to redistribution of key transcription factors in prostate cancers positive for the TMPRSS2-ERG fusion gene. The overexpression of ERG is further assisted by the development of a super-enhancer in the ERG locus.

    • Deepak Babu
    •  & Melissa J Fullwood
  • News and Views |

    An innovative study analyzing genetic association across tree-structured routine healthcare data in the UK Biobank represents a new branch on a tree that is poised to grow rapidly and offer new kinds of insights on how genome variation relates to human health and disease. Indeed, this tree is likely to offer new kinds of insights into the very nature of human disease.

    • Nancy J Cox

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