A global reference for human genetic variation

The 1000 Genomes Project set out to provide a comprehensive description of common human genetic variation by applying whole-genome sequencing to a diverse set of individuals from multiple populations. Here we report completion of the project, having reconstructed the genomes of 2,504 individuals from 26 populations using a combination of low-coverage whole-genome sequencing, deep exome sequencing, and dense microarray genotyping. We characterized a broad spectrum of genetic variation, in total over 88 million variants (84.7 million single nucleotide polymorphisms (SNPs), 3.6 million short insertions/deletions (indels), and 60,000 structural variants), all phased onto high-quality haplotypes. This resource includes >99% of SNP variants with a frequency of >1% for a variety of ancestries. We describe the distribution of genetic variation across the global sample, and discuss the implications for common disease studies.Organismic and Evolutionary Biolog

A Malaria Fingerprint in the Human Genome?

Organismic and Evolutionary Biolog

Clinical Sequencing Uncovers Origins and Evolution of Lassa Virus

The 2013-2015 West African epidemic of Ebola virus disease (EVD) reminds us how little is known about biosafety level-4 viruses. Like Ebola virus, Lassa virus (LASV) can cause hemorrhagic fever with high case fatality rates. We generated a genomic catalog of almost 200 LASV sequences from clinical and rodent reservoir samples. We show that whereas the 2013-2015 EVD epidemic is fueled by human-to-human transmissions, LASV infections mainly result from reservoir-to-human infections. We elucidated the spread of LASV across West Africa and show that this migration was accompanied by changes in LASV genome abundance, fatality rates, codon adaptation, and translational efficiency. By investigating intrahost evolution, we found that mutations accumulate in epitopes of viral surface proteins, suggesting selection for immune escape. This catalog will serve as a foundation for the development of vaccines and diagnostics.Organismic and Evolutionary Biolog

The Landscape of Human Evolution

Organismic and Evolutionary BiologyOther Research Uni

Containing the spread of mumps on college campuses

College campuses are vulnerable to infectious disease outbreaks, and there is an urgent need to develop better strategies to mitigate their size and duration, particularly as educational institutions around the world adapt to in-person instruction during the COVID-19 pandemic. Towards addressing this need, we applied a stochastic compartmental model to quantify the impact of university-level responses to contain a mumps outbreak at Harvard University in 2016. We used our model to determine which containment interventions were most effective and study alternative scenarios without and with earlier interventions. This model allows for stochastic variation in small populations, missing or unobserved case data and changes in disease transmission rates post-intervention. The results suggest that control measures implemented by the University\u27s Health Services, including rapid isolation of suspected cases, were very effective at containing the outbreak. Without those measures, the outbreak could have been four times larger. More generally, we conclude that universities should apply (i) diagnostic protocols that address false negatives from molecular tests and (ii) strict quarantine policies to contain the spread of easily transmissible infectious diseases such as mumps among their students. This modelling approach could be applied to data from other outbreaks in college campuses and similar small population settings