De novo human genome assemblies reveal spectrum of alternative haplotypes in diverse populations.

The human reference genome is used extensively in modern biological research. However, a single consensus representation is inadequate to provide a universal reference structure because it is a haplotype among many in the human population. Using 10× Genomics (10×G) "Linked-Read" technology, we perform whole genome sequencing (WGS) and de novo assembly on 17 individuals across five populations. We identify 1842 breakpoint-resolved non-reference unique insertions (NUIs) that, in aggregate, add up to 2.1 Mb of so far undescribed genomic content. Among these, 64% are considered ancestral to humans since they are found in non-human primate genomes. Furthermore, 37% of the NUIs can be found in the human transcriptome and 14% likely arose from Alu-recombination-mediated deletion. Our results underline the need of a set of human reference genomes that includes a comprehensive list of alternative haplotypes to depict the complete spectrum of genetic diversity across populations

Comprehensive Analysis of Human Subtelomeres by Whole Genome Mapping

Detailed comprehensive knowledge of the structures of individual long-range telomere-terminal haplotypes are needed to understand their impact on telomere function, and to delineate the population structure and evolution of subtelomere regions. However, the abundance of large evolutionarily recent segmental duplications and high levels of large structural variations have complicated both the mapping and sequence characterization of human subtelomere regions. Here, we use high throughput optical mapping of large single DNA molecules in nanochannel arrays for 154 human genomes from 26 populations to present a comprehensive look at human subtelomere structure and variation. The results catalog many novel long-range subtelomere haplotypes and determine the frequencies and contexts of specific subtelomeric duplicons on each chromosome arm, helping to clarify the currently ambiguous nature of many specific subtelomere structures as represented in the current reference sequence (HG38). The organization and content of some duplicons in subtelomeres appear to show both chromosome arm and population-specific trends. Based upon these trends we estimate a timeline for the spread of these duplication blocks

Application of next generation sequencing to CEPH cell lines to discover variants associated with FDA approved chemotherapeutics

After publication of this work [1], it has come to our attention that there is an error in the author list of the initial version of this manuscript; rather than Ernest J Lam, the second author of the manuscript should be listed as Ernest T Lam

Genome sequence and genetic linkage analysis of Shiitake mushroom _Lentinula edodes_

_Lentinula edodes_ (Shiitake/Xianggu) is an important cultivated mushroom. Understanding the genomics and functional genomics of _L. edodes_ allows us to improve its cultivation and quality. Genome sequence is a key to develop molecular genetic markers for breeding and genetic manipulation. We sequenced the genome of _L. edodes_ monokaryon L54A using Roche 454 and ABI SOLiD genome sequencing. Sequencing reads of about 1400Mb were de novo assembled into a 40.2 Mb genome sequence. We compiled the genome sequence into a searchable database with which we have been annotating the genes and analyzing the metabolic pathways. In addition, we have been using many molecular techniques to analyze genes differentially expressed during development. Gene ortholog groups of _L. edodes_ genome sequence compared across genomes of several fungi including mushrooms identified gene families unique to mushroom-forming fungi. We used a mapping population of haploid basidiospores of dikaryon L54 for genetic linkage analysis. High-quality variations such as single nucleotide polymorphisms, insertions, and deletions of the mapping population formed a high-density genetic linkage map. We compared the linkage map to the _L. edodes_ L54A genome sequence and located selected quantitative trait loci. The Shiitake community will benefit from these resources for genetic studies and breeding.
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SNPs Meet CNVs in Genome-Wide Association Studies: HGV2007 Meeting Report

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OMMA enables population-scale analysis of complex genomic features and phylogenomic relationships from nanochannel-based optical maps.

BackgroundOptical mapping is an emerging technology that complements sequencing-based methods in genome analysis. It is widely used in improving genome assemblies and detecting structural variations by providing information over much longer (up to 1 Mb) reads. Current standards in optical mapping analysis involve assembling optical maps into contigs and aligning them to a reference, which is limited to pairwise comparison and becomes bias-prone when analyzing multiple samples.FindingsWe present a new method, OMMA, that extends optical mapping to the study of complex genomic features by simultaneously interrogating optical maps across many samples in a reference-independent manner. OMMA captures and characterizes complex genomic features, e.g., multiple haplotypes, copy number variations, and subtelomeric structures when applied to 154 human samples across the 26 populations sequenced in the 1000 Genomes Project. For small genomes such as pathogenic bacteria, OMMA accurately reconstructs the phylogenomic relationships and identifies functional elements across 21 Acinetobacter baumannii strains.ConclusionsWith the increasing data throughput of optical mapping system, the use of this technology in comparative genome analysis across many samples will become feasible. OMMA is a timely solution that can address such computational need. The OMMA software is available at https://github.com/TF-Chan-Lab/OMTools

SNPs Meet CNVs in Genome-Wide Association Studies: HGV2007 Meeting Report

SNPs meet CNVs in genome-wide association studies: HGV2007 meeting repor

Genomic variation in a global village: Report of the 10th annual Human Genome Variation Meeting 2008

The Centre for Applied Genomics of the Hospital for Sick Children and the University of Toronto hosted the 10th Human Genome Variation (HGV) Meeting in Toronto, Canada, in October 2008, welcoming about 240 registrants from 34 countries. During the 3 days of plenary workshops, keynote address, and poster sessions, a strong cross-disciplinary trend was evident, integrating expertise from technology and computation, through biology and medicine, to ethics and law. Single nucleotide polymorphisms (SNPs) as well as the larger copy number variants (CNVs) are recognized by ever-improving array and next-generation sequencing technologies, and the data are being incorporated into studies that are increasingly genome-wide as well as global in scope. A greater challenge is to convert data to information, through databases, and to use the information for greater understanding of human variation. In the wake of publications of the first individual genome sequences, an inaugural public forum provided the opportunity to debate whether we are ready for personalized medicine through direct-to-consumer testing. The HGV meetings foster collaboration, and fruits of the interactions from 2008 are anticipated for the 11th annual meeting in September 2009. Hum Mutat 30:1–5, 2009. © 2009 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63049/1/21008_ftp.pd