In this week's Nature, the 1,000 Genomes Project Consortium reports results from its pilot phase, which included three projects: "low-coverage whole-genome sequencing of 179 individuals from four populations, high-coverage sequencing of two mother-father-child trios, and exon-targeted sequencing of 697 individuals from seven populations." In its paper, the 1,000 Genomes team shares the "location, allele frequency and local haplotype structure of approximately 15 million SNPs, 1 million short insertions and deletions, and 20,000 structural variants, most of which were previously undescribed." In addition, the team reports that each individual was found to carry 250 to 300 loss-of-function variants in annotated genes and 50 to 100 variants associated with inherited disorders, on average. "Data from the mother-father-child trios suggest a germline base substitution rate of 10-8 per base pair per generation," the researchers add.
In another Nature paper published this week, researchers at DeCode Genetics report the "fine-scale recombination rate differences between sexes, populations and individuals," which they've determined using genome-wide SNP data from more than 15,000 parent-offspring pairs. The team was able to map recombination at an effective resolution of "down to 10 kb"; from this, the DeCode researchers found that "15 percent of hotspots in one sex are specific to that sex," and that "female recombinations generate more new combinations of nearby genes." Furthermore, the team identified "novel associations between recombination characteristics of individuals and variants in the PRDM9 gene."
Investigators from the Wellcome Trust Sanger Institute's Cancer Genome Project this week discuss "the patterns and dynamics of genomic instability in metastatic pancreatic cancer." The CGP team sequenced samples from 13 pancreatic cancer patients in order to annotate the genomic rearrangements and "explore clonal relationships among metastases. The researchers found that "pancreatic cancer acquires rearrangements indicative of telomere dysfunction and abnormal cell-cycle control," and evidence for "genetic heterogeneity among metastasis-initiating cells."
In a related paper, investigators delve into pancreatic cancer metastasis. Using sequencing data from seven pancreatic cancer metastases, the group shows that "clonal populations that give rise to distant metastases are represented within the primary carcinoma, but these clones are genetically evolved from the original parental, non-metastatic clone," which is reflected by heterogeneity within the primary carcinoma. The team suggests that "distant metastasis occurs late during the genetic evolution of pancreatic cancer."