Computational pan-genomics: Status, promises and challenges

Many disciplines, from human genetics and oncology to plant breeding, microbiology and virology, commonly face the challenge of analyzing rapidly increasing numbers of genomes. In case of Homo sapiens, the number of sequenced genomes will approach hundreds of thousands in the next few years. Simply scaling up established bioinformatics pipelines will not be sufficient for leveraging the full potential of such rich genomic data sets. Instead, novel, qualitatively different Computational methods and paradigms are needed.We will witness the rapid extension of Computational pan-genomics, a new sub-area of research in Computational biology. In this article, we generalize existing definitions and understand a pangenome as any collection of genomic sequences to be analyzed jointly or to be used as a reference. We examine already available approaches to construct and use pan-genomes, discuss the potential benefits of future technologies and methodologies and review open challenges from the vantage point of the above-mentioned biological disciplines. As a prominent example for a Computational paradigm shift, we particularly highlight the transition from the representation of reference genomes as strings to representations

Erratum: Corrigendum: Sequence and comparative analysis of the chicken genome provide unique perspectives on vertebrate evolution

International Chicken Genome Sequencing Consortium. The Original Article was published on 09 December 2004. Nature432, 695–716 (2004). In Table 5 of this Article, the last four values listed in the ‘Copy number’ column were incorrect. These should be: LTR elements, 30,000; DNA transposons, 20,000; simple repeats, 140,000; and satellites, 4,000. These errors do not affect any of the conclusions in our paper. Additional information. The online version of the original article can be found at 10.1038/nature0315

Complete Khoisan and Bantu genomes from southern Africa

The genetic structure of the indigenous hunter-gatherer peoples of southern Africa, the oldest known lineage of modern human, is important for understanding human diversity. Studies based on mitochondrial(1) and small sets of nuclear markers(2) have shown that these hunter-gatherers, known as Khoisan, San, or Bushmen, are genetically divergent from other humans(1,3). However, until now, fully sequenced human genomes have been limited to recently diverged populations(4–8). Here we present the complete genome sequences of an indigenous hunter-gatherer from the Kalahari Desert and a Bantu from southern Africa, as well as protein-coding regions from an additional three hunter-gatherers from disparate regions of the Kalahari. We characterize the extent of whole-genome and exome diversity among the five men, reporting 1.3 million novel DNA differences genome-wide, including 13,146 novel amino acid variants. In terms of nucleotide substitutions, the Bushmen seem to be, on average, more different from each other than, for example, a European and an Asian. Observed genomic differences between the hunter-gatherers and others may help to pinpoint genetic adaptations to an agricultural lifestyle. Adding the described variants to current databases will facilitate inclusion of southern Africans in medical research efforts, particularly when family and medical histories can be correlated with genome-wide data

Supotsu to boken monogatari

<p><b>ITP results using the mean difference as test statistics for (A) recombination hotspots (localized differential landscape–LDL) and (B) mononucleotide microsatellites (invariant differential landscape–IDL) in the flanking regions of fixed ETn vs. controls.</b> The heatmap in the top panel shows the p-values for each component (i.e. window; horizontal axis) corrected controlling the family-wise error rate on all possible maximum interval lengths (vertical axis). Blue corresponds to low p-values, hence significant differences between the distributions underlying the flanking regions of ERVs and the controls. The middle panel shows corrected p-values at the chosen maximum interval length threshold, with gray highlighting significant components (corrected p-values<0.05). The lower panels show the average of the genome feature under consideration over the flanking regions of all fixed ETns (red line) and controls (green line). First and third quartiles (25% and 75% quantiles) are shaded in the respective colors–red for ETns and green for controls. The shades for control are invisible because they are zeros for control. The heatmap suggests the scales (vertical axis) and the locations (horizontal axis) at which the feature is significant to characterize ERVs genomic landscape.</p

Sequence and comparative analysis of the chicken genome provide unique perspectives on vertebrate evolution

We present here a draft genome sequence of the red jungle fowl, Gallus gallus. Because the chicken is a modern descendant of the dinosaurs and the first non-mammalian amniote to have its genome sequenced, the draft sequence of its genome--composed of approximately one billion base pairs of sequence and an estimated 20,000-23,000 genes--provides a new perspective on vertebrate genome evolution, while also improving the annotation of mammalian genomes. For example, the evolutionary distance between chicken and human provides high specificity in detecting functional elements, both non-coding and coding. Notably, many conserved non-coding sequences are far from genes and cannot be assigned to defined functional classes. In coding regions the evolutionary dynamics of protein domains and orthologous groups illustrate processes that distinguish the lineages leading to birds and mammals. The distinctive properties of avian microchromosomes, together with the inferred patterns of conserved synteny, provide additional insights into vertebrate chromosome architecture

Genome Sequence of the Brown Norway Rat Yields Insights Into Mammalian Evolution

The laboratory rat (Rattus norvegicus) is an indispensable tool in experimental medicine and drug development, having made inestimable contributions to human health. We report here the genome sequence of the Brown Norway (BN) rat strain. The sequence represents a high-quality 'draft' covering over 90% of the genome. The BN rat sequence is the third complete mammalian genome to be deciphered, and three-way comparisons with the human and mouse genomes resolve details of mammalian evolution. This first comprehensive analysis includes genes and proteins and their relation to human disease, repeated sequences, comparative genome-wide studies of mammalian orthologous chromosomal regions and rearrangement breakpoints, reconstruction of ancestral karyotypes and the events leading to existing species, rates of variation, and lineage-specific and lineage-independent evolutionary events such as expansion of gene families, orthology relations and protein evolution