Lineage-Specific Biology Revealed by a Finished Genome Assembly of the Mouse

The mouse (Mus musculus) is the premier animal model for understanding human disease and development. Here we show that a comprehensive understanding of mouse biology is only possible with the availability of a finished, high-quality genome assembly. The finished clone-based assembly of the mouse strain C57BL/6J reported here has over 175,000 fewer gaps and over 139 Mb more of novel sequence, compared with the earlier MGSCv3 draft genome assembly. In a comprehensive analysis of this revised genome sequence, we are now able to define 20,210 protein-coding genes, over a thousand more than predicted in the human genome (19,042 genes). In addition, we identified 439 long, non–protein-coding RNAs with evidence for transcribed orthologs in human. We analyzed the complex and repetitive landscape of 267 Mb of sequence that was missing or misassembled in the previously published assembly, and we provide insights into the reasons for its resistance to sequencing and assembly by whole-genome shotgun approaches. Duplicated regions within newly assembled sequence tend to be of more recent ancestry than duplicates in the published draft, correcting our initial understanding of recent evolution on the mouse lineage. These duplicates appear to be largely composed of sequence regions containing transposable elements and duplicated protein-coding genes; of these, some may be fixed in the mouse population, but at least 40% of segmentally duplicated sequences are copy number variable even among laboratory mouse strains. Mouse lineage-specific regions contain 3,767 genes drawn mainly from rapidly-changing gene families associated with reproductive functions. The finished mouse genome assembly, therefore, greatly improves our understanding of rodent-specific biology and allows the delineation of ancestral biological functions that are shared with human from derived functions that are not.

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Lineage-Specific Biology Revealed by a Finished Genome Assembly of the Mouse

The Genetics and Genomics of Infectious Diseases 2009

Classical and emerging infectious diseases, viral pandemics, and drug-resistant pathogens remain challenges to human health. However, contemporary advances in genetics and genomic technologies provide new approaches to understanding and combating these diseases. ASHG and HUGO are partnering with NPG to organize an international conference to discuss how the genomes, unique biologies, and interactions of both host and pathogen are being revealed using novel genomic technologies, and how this information can and will translate into disease management and therapies. This conference will engage basic and clinical scientists, including human geneticists, genome scientists, computational biologists, and experts in pathogenic microbial agents to chart the effects of genomics on questions in global infectious disease management.

For more information and to register visit: www.nature.com/natureconferences/ggid2009

Interpreting the Human Genome- THE MIAMI 2009 WINTER SYMPOSIUM

The human genome has hidden levels of regulatory complexity and variability that have begun to reveal themselves since the initial sequence became available in 2001. Today, with increasingly powerful sequencing and analysis technologies, we are not only beginning to appreciate the scale of variation in individual human genome sequences, but also gaining a greater understanding of how genome differences relate to human evolution and disease. This meeting will showcase these advances in our understanding of human genome regulation and variability as well as the potential of new technologies to drive the advancement of knowledge.

January 24-28, 2009
Deauville Beach Resort
Miami Beach, FL, USA

SESSION TOPICS
Beyond the Sequence
Genome Variation
Genome Variation and Disease
Genome-wide Associations and Disease
Emerging Technologies for Human Genome Studies
Toward Therapy

SYMPOSIUM AWARDEES
Feodor Lynen Lecture:
Svante Pääbo (Max Planck Institute for Evolutionary Anthropology, Germany)
Distinguished Service Award:
J. Craig Venter (J. Craig Venter Institute, USA)
Special Achievement Award:
George M. Church (Harvard Medical School, USA)

SPEAKERS
Donna Albertson (University of California - San Francisco, USA)
Arthur Beaudet (Baylor College of Medicine, USA)
David Bentley (Illumina Inc., UK / USA)
Andrew G. Clark (Cornell University, USA)
Evan Eichler (University of Washington, USA)
Andrew Feinberg (Johns Hopkins School of Medicine, USA)
Richard Gibbs (Baylor College of Medicine, USA)
Tom Gingeras (Affymetrix/CSL, USA)
David Goldstein (Duke University, USA)
Jonathan Haines (Vanderbilt University, USA)
James R. Lupski (Baylor College of Medicine, USA)
John Mattick (The University of Queensland, Australia)
Mark I. McCarthy (The Oxford Centre for Diabetes, Endocrinology and Metabolism, UK)
Alex Meissner (Harvard University / The Broad Institute of MIT and Harvard, USA)
Patrice Milos (Helicos Biosciences Corporation, USA)
Margaret Pericak-Vance (University of Miami Miller School of Medicine, USA)
Allen Roses (Duke University, USA)
Stephen Scherer (The Hospital for Sick Children/University of Toronto, Canada)
Eric Topol (Scripps Clinic, USA)
Michael Wigler (Cold Spring Harbor Laboratory, USA)

For more information and to register visit: www.nature.com/natureconferences/MWS2009

Sequencing the mammoth genome

In 1994, two independent groups extracted DNA from several Pleistocene epoch mammoths and noted differences among individual specimens. Subsequently, DNA sequences have been published for a number of extinct species. However, such ancient DNA is often fragmented and damaged, and studies to date have typically focused on short mitochondrial sequences, never yielding more than a fraction of a per cent of any nuclear genome. Here we describe 4.17 billion bases (Gb) of sequence from several mammoth specimens, 3.3 billion (80%) of which are from the woolly mammoth (Mammuthus primigenius) genome and thus comprise an extensive set of genome-wide sequence from an extinct species. Our data support earlier reports that elephantid genomes exceed 4 Gb. The estimated divergence rate between mammoth and African elephant is half of that between human and chimpanzee. The observed number of nucleotide differences between two particular mammoths was approximately one-eighth of that between one of them and the African elephant, corresponding to a separation between the mammoths of 1.5–2.0 Myr. The estimated probability that orthologous elephant and mammoth amino acids differ is 0.002, corresponding to about one residue per protein. Differences were discovered between mammoth and African elephant in amino-acid positions that are otherwise invariant over several billion years of combined mammalian evolution. This study shows that nuclear genome sequencing of extinct species can reveal population differences not evident from the fossil record, and perhaps even discover genetic factors that affect extinction.


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Sequencing the nuclear genome of the extinct woolly mammoth. Webb Miller et al. Nature 456, 387-390 (20 November 2008).

Genes and Social Behavior

What genes and regulatory sequences contribute to the organization and functioning of neural circuits and molecular pathways in the brain that support social behavior? How does social experience interact with information in the genome to modulate brain activity? Here, we address these questions by highlighting progress that has been made in identifying and understanding two key "vectors of influence" that link genes, the brain, and social behavior: (i) Social information alters gene expression in the brain to influence behavior, and (ii) genetic variation influences brain function and social behavior. We also discuss how evolutionary changes in genomic elements influence social behavior and outline prospects for a systems biology of social behavior.

Sources:

Genes and Social Behavior. Robinson et al. Science 7 November 2008, Vol. 322. no. 5903, pp. 896 - 900.