South Asia's multiple founder populations

Latest Research

  • 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
  • Analysis |

    Steven Gazal, Alkes Price and colleagues extend stratified LD score regression to continuous annotations. They analyze summary statistics from 56 complex diseases and traits and find that SNPs with low levels of linkage disequilibrium have larger per-SNP heritability, consistent with the action of negative selection on deleterious variants that affect complex traits.

    • Steven Gazal
    • , Hilary K Finucane
    • , Nicholas A Furlotte
    • , Po-Ru Loh
    • , Pier Francesco Palamara
    • , Xuanyao Liu
    • , Armin Schoech
    • , Brendan Bulik-Sullivan
    • , Benjamin M Neale
    • , Alexander Gusev
    •  & Alkes L Price
  • Article |

    Eric Schadt and colleagues present a predictive causal model of the immune component of inflammatory bowel disease through integration of genetic, regulatory and transcriptional data. They prioritize and validate 12 of the top key drivers experimentally in mouse colitis models and human macrophages.

    • Lauren A Peters
    • , Jacqueline Perrigoue
    • , Arthur Mortha
    • , Alina Iuga
    • , Won-min Song
    • , Eric M Neiman
    • , Sean R Llewellyn
    • , Antonio Di Narzo
    • , Brian A Kidd
    • , Shannon E Telesco
    • , Yongzhong Zhao
    • , Aleksandar Stojmirovic
    • , Jocelyn Sendecki
    • , Khader Shameer
    • , Riccardo Miotto
    • , Bojan Losic
    • , Hardik Shah
    • , Eunjee Lee
    • , Minghui Wang
    • , Jeremiah J Faith
    • , Andrew Kasarskis
    • , Carrie Brodmerkel
    • , Mark Curran
    • , Anuk Das
    • , Joshua R Friedman
    • , Yoshinori Fukui
    • , Mary Beth Humphrey
    • , Brian M Iritani
    • , Nicholas Sibinga
    • , Teresa K Tarrant
    • , Carmen Argmann
    • , Ke Hao
    • , Panos Roussos
    • , Jun Zhu
    • , Bin Zhang
    • , Radu Dobrin
    • , Lloyd F Mayer
    •  & Eric E Schadt
  • Article |

    Yoichiro Kamatani and colleagues perform a genome-wide association study (GWAS) for body mass index using data from 173,430 Japanese individuals. They find 85 significant loci, 51 of which are novel, and use trans-ancestral meta-analysis of GWAS from European samples to identify 61 additional new loci.

    • Masato Akiyama
    • , Yukinori Okada
    • , Masahiro Kanai
    • , Atsushi Takahashi
    • , Yukihide Momozawa
    • , Masashi Ikeda
    • , Nakao Iwata
    • , Shiro Ikegawa
    • , Makoto Hirata
    • , Koichi Matsuda
    • , Motoki Iwasaki
    • , Taiki Yamaji
    • , Norie Sawada
    • , Tsuyoshi Hachiya
    • , Kozo Tanno
    • , Atsushi Shimizu
    • , Atsushi Hozawa
    • , Naoko Minegishi
    • , Shoichiro Tsugane
    • , Masayuki Yamamoto
    • , Michiaki Kubo
    •  & Yoichiro Kamatani
  • Letter |

    Robert Graham and colleagues carried out a GWAS meta-analysis for Parkinson's disease (PD) and report 17 new risk loci. Their analyses support a key role for autophagy and lysosomal biology in PD risk.

    • Diana Chang
    • , Mike A Nalls
    • , Ingileif B Hallgrímsdóttir
    • , Julie Hunkapiller
    • , Marcel van der Brug
    • , Fang Cai
    • , International Parkinson's Disease Genomics Consortium
    • , 23andMe Research Team
    • , Geoffrey A Kerchner
    • , Gai Ayalon
    • , Baris Bingol
    • , Morgan Sheng
    • , David Hinds
    • , Timothy W Behrens
    • , Andrew B Singleton
    • , Tushar R Bhangale
    •  & Robert R Graham

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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