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.

Next-generation massively parallel DNA sequencing technologies provide ultrahigh throughput at a substantially lower unit data cost; however, the data are very short read length sequences, making de novo assembly extremely challenging. Here, we describe a novel method for de novo assembly of large genomes from short read sequences. We successfully assembled both the Asian and African human genome sequences, achieving an N50 contig size of 7.4 and 5.9 kilobases (kb) and scaffold of 446.3 and 61.9 kb, respectively. The development of this de novo short read assembly method creates new opportunities for building reference sequences and carrying out accurate analyses of unexplored genomes in a cost-effective way.

The Pacific oyster Crassostrea gigas belongs to one of the most species-rich but genomically poorly explored phyla, the Mollusca. Here we report the sequencing and assembly of the oyster genome using short reads and a fosmid-pooling strategy, along with transcriptomes of development and stress response and the proteome of the shell. The oyster genome is highly polymorphic and rich in repetitive sequences, with some transposable elements still actively shaping variation. Transcriptome studies reveal an extensive set of genes responding to environmental stress. The expansion of genes coding for heat shock protein 70 and inhibitors of apoptosis is probably central to the oyster's adaptation to sessile life in the highly stressful intertidal zone. Our analyses also show that shell formation in molluscs is more complex than currently understood and involves extensive participation of cells and their exosomes. The oyster genome sequence fills a void in our understanding of the Lophotrochozoa.Oceans cover approximately 71% of the Earth's surface and harbour most of the phylum diversity of the animal kingdom. Understanding marine biodiversity and its evolution remains a major challenge. The Pacific oyster C. gigas (Thunberg, 1793) is a marine bivalve belonging to the phylum Mollusca, which contains the largest number of described marine animal species 1 . Molluscs have vital roles in the functioning of marine, freshwater and terrestrial ecosystems, and have had major effects on humans, primarily as food sources but also as sources of dyes, decorative pearls and shells, vectors of parasites, and biofouling or destructive agents. Many molluscs are important fishery and aquaculture species, as well as models for studying neurobiology, biomineralization, ocean acidification and adaptation to coastal environments under climate change 2,3 . As the most speciose member of the Lophotrochozoa, phylum Mollusca is central to our understanding of the biology and evolution of this superphylum of protostomes.As sessile marine animals living in estuarine and intertidal regions, oysters must cope with harsh and dynamically changing environments. Abiotic factors such as temperature and salinity fluctuate wildly, and toxic metals and desiccation also pose serious challenges. Filter-feeding oysters face tremendous exposure to microbial pathogens. Oysters do have a notable physical line of defence against predation and desiccation in the formation of thick calcified shells, a key evolutionary innovation making molluscs a successful group. However, acidification of the world's oceans by uptake of anthropogenic carbon dioxide poses a potentially serious threat to this ancient adaptation 4 . Understanding biomineralization and molluscan shell formation is, thus, a major area of interest 5 . Crassostrea gigas is also an interesting model for developmental biology owing to its mosaic development with typical molluscan stages, including trochophore and veliger larvae and metamorphosis.A complete genome sequence of C. gigas would enable a more th...

Here we analyse genetic variation, population structure and diversity among 3,010 diverse Asian cultivated rice (Oryza sativa L.) genomes from the 3,000 Rice Genomes Project. Our results are consistent with the five major groups previously recognized, but also suggest several unreported subpopulations that correlate with geographic location. We identified 29 million single nucleotide polymorphisms, 2.4 million small indels and over 90,000 structural variations that contribute to within-and between-population variation. Using pan-genome analyses, we identified more than 10,000 novel full-length protein-coding genes and a high number of presence-absence variations. The complex patterns of introgression observed in domestication genes are consistent with multiple independent rice domestication events. The public availability of data from the 3,000 Rice Genomes Project provides a resource for rice genomics research and breeding.Asian cultivated rice is grown worldwide and comprises the staple food for half of the global population. It is envisaged that by the year 2035 1 feeding this growing population will necessitate that an additional 112 million metric tons of rice be produced on a smaller area of land, using less water and under more fluctuating climatic conditions, which will require that future rice cultivars be higher yielding and resilient to multiple abiotic and biotic stresses. The foundation of the continued improvement of rice cultivars is the rich genetic diversity within domesticated populations and wild relatives [2][3][4] . For over 2,000 years, two major types of O. sativa-O. sativa Xian group (here referred to as Xian/Indica (XI) and also known as , Hsien or Indica) and O. sativa Geng Group (here referred to as Geng/Japonica (GJ) and also known as , Keng or Japonica)-have historically been recognized [5][6][7] . Varied degrees of post-reproductive barriers exist between XI and GJ rice accessions 8 ; this differentiation between XI and GJ rice types and the presence of different varietal groups are well-documented at isozyme and DNA levels 6,9 . Two other distinct groups have also been recognized using molecular markers 10 ; one of these encompasses the Aus, Boro and Rayada ecotypes from Bangladesh and India (which we term the circum-Aus group (cA)) and the other comprises the famous Basmati and Sadri aromatic varieties (which we term the circum-Basmati group (cB)).Approximately 780,000 rice accessions are available in gene banks worldwide 11 . To enable the more efficient use of these accessions in future rice improvement, the Chinese Academy of Agricultural Sciences, BGI-Shenzhen and International Rice Research Institute sequenced over 3,000 rice genomes (3K-RG) as part of the 3,000 Rice Genomes Project 12. Here we present analyses of genetic variation in the 3K-RG that focus on important aspects of O. sativa diversity, single nucleotide polymorphisms (SNPs) and structural variation (deletions, duplications, inversions and translocations). We also construct a species pangenome consisting of 'core...

Amyotrophic lateral sclerosis (ALS) is a devastating human neurodegenerative disease. The causes of ALS are poorly understood, although the protein TDP-43 has been suggested to play a critical role in disease pathogenesis. Here we show that Ataxin-2, a polyglutamine (polyQ) protein mutated in spinocerebellar ataxia type 2 (SCA2), is a potent modifier of TDP-43 toxicity in animal and cellular models. The proteins associate in a complex that depends on RNA. Ataxin-2 is abnormally localized in spinal cord neurons of ALS patients. Likewise, TDP-43 shows mislocalization in SCA2. To assess a role in ALS, we analyzed the Ataxin-2 gene (ATXN2) in 915 ALS patients. We found intermediate-length polyQ expansions (27–33 Qs) in ATXN2 significantly associated with ALS. These data establish ATXN2 as a relatively common ALS disease susceptibility gene. Further, these findings indicate that the TDP-43/Ataxin-2 interaction may be a promising target for therapeutic intervention in ALS and other TDP-43 proteinopathies.