Dark matter maps reveal cosmic scaffolding

Ordinary baryonic particles (such as protons and neutrons) account for only one-sixth of the total matter in the Universe. The remainder is a mysterious 'dark matter' component, which does not interact via electromagnetism and thus neither emits nor reflects light. As dark matter cannot be seen directly using traditional observations, very little is currently known about its properties. It does interact via gravity, and is most effectively probed through gravitational lensing: the deflection of light from distant galaxies by the gravitational attraction of foreground mass concentrations. This is a purely geometrical effect that is free of astrophysical assumptions and sensitive to all matter--whether baryonic or dark. Here we show high-fidelity maps of the large-scale distribution of dark matter, resolved in both angle and depth. We find a loose network of filaments, growing over time, which intersect in massive structures at the locations of clusters of galaxies. Our results are consistent with predictions of gravitationally induced structure formation, in which the initial, smooth distribution of dark matter collapses into filaments then into clusters, forming a gravitational scaffold into which gas can accumulate, and stars can be built.     

Efficient mapping of mendelian traits in dogs through genome-wide association

With several hundred genetic diseases and an advantageous genome structure, dogs are ideal for mapping genes that cause disease. Here we report the development of a genotyping array with approximately 27,000 SNPs and show that genome-wide association mapping of mendelian traits in dog breeds can be achieved with only approximately 20 dogs. Specifically, we map two traits with mendelian inheritance: the major white spotting (S) locus and the hair ridge in Rhodesian ridgebacks. For both traits, we map the loci to discrete regions of <1 Mb. Fine-mapping of the S locus in two breeds refines the localization to a region of approximately 100 kb contained within the pigmentation-related gene MITF. Complete sequencing of the white and solid haplotypes identifies candidate regulatory mutations in the melanocyte-specific promoter of MITF. Our results show that genome-wide association mapping within dog breeds, followed by fine-mapping across multiple breeds, will be highly efficient and generally applicable to trait mapping, providing insights into canine and human health.     

Measurement of the human allele frequency spectrum demonstrates greater genetic drift in East Asians than in Europeans

Large data sets on human genetic variation have been collected recently, but their usefulness for learning about history and natural selection has been limited by biases in the ways polymorphisms were chosen. We report large subsets of SNPs from the International HapMap Project that allow us to overcome these biases and to provide accurate measurement of a quantity of crucial importance for understanding genetic variation: the allele frequency spectrum. Our analysis shows that East Asian and northern European ancestors shared the same population bottleneck expanding out of Africa but that both also experienced more recent genetic drift, which was greater in East Asians.     

A canine DNM1 mutation is highly associated with the syndrome of exercise-induced collapse

Labrador retrievers are the most common dog breed in the world, with over 200,000 new kennel club registrations per year. The syndrome of exercise-induced collapse (EIC) in this breed is manifested by muscle weakness, incoordination and life-threatening collapse after intense exercise. Using a genome-wide microsatellite marker scan for linkage in pedigrees, we mapped the EIC locus to canine chromosome 9. We then used SNP association and haplotype analysis to fine map the locus, and identified a mutation in the dynamin 1 gene (DNM1) that causes an R256L substitution in a highly conserved region of the protein. This first documented mammalian DNM1 mutation is present at a high frequency in the breed and is a compelling candidate causal mutation for EIC, as the dynamin 1 protein has an essential role in neurotransmission and synaptic vesicle endocytosis.     

Closing gaps in the human genome with fosmid resources generated from multiple individuals

The human genome sequence has been finished to very high standards; however, more than 340 gaps remained when the finished genome was published by the International Human Genome Sequencing Consortium in 2004. Using fosmid resources generated from multiple individuals, we targeted gaps in the euchromatic part of the human genome. Here we report 2,488,842 bp of previously unknown euchromatic sequence, 363,114 bp of which close 26 of 250 euchromatic gaps, or 10%, including two remaining euchromatic gaps on chromosome 19. Eight (30.7%) of the closed gaps were found to be polymorphic. These sequences allow complete annotation of several human genes as well as the assignment of mRNAs. The gap sequences are 2.3-fold enriched in segmentally duplicated sequences compared to the whole genome. Our analysis confirms that not all gaps within 'finished' genomes are recalcitrant to subcloning and suggests that the paired-end-sequenced fosmid libraries could prove to be a rich resource for completion of the human euchromatic genome.     

Genetic determinants of ulcerative colitis include the ECM1 locus and five loci implicated in Crohn's disease

We report results of a nonsynonymous SNP scan for ulcerative colitis and identify a previously unknown susceptibility locus at ECM1. We also show that several risk loci are common to ulcerative colitis and Crohn's disease (IL23R, IL12B, HLA, NKX2-3 and MST1), whereas autophagy genes ATG16L1 and IRGM, along with NOD2 (also known as CARD15), are specific for Crohn's disease. These data provide the first detailed illustration of the genetic relationship between these common inflammatory bowel diseases.