The results of an international collaboration to produce and make freely available a draft sequence of the human genome are reported and an initial analysis is presented, describing some of the insights that can be gleaned from the sequence.
The nucleotide sequence of nearly all of the approximately 120-megabase euchromatic portion of the Drosophila genome is determined using a whole-genome shotgun sequencing strategy supported by extensive clone-based sequence and a high-quality bacterial artificial chromosome physical map.
A comprehensive search for conserved elements in vertebrate genomes is conducted, using genome-wide multiple alignments of five vertebrate species (human, mouse, rat, chicken, and Fugu rubripes), using a two-state phylogenetic hidden Markov model (phylo-HMM).
The Phase II HapMap is described, which characterizes over 3.1 million human single nucleotide polymorphisms genotyped in 270 individuals from four geographically diverse populations and includes 25–35% of common SNP variation in the populations surveyed, and increased differentiation at non-synonymous, compared to synonymous, SNPs is demonstrated.
Functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project are reported, providing convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts.
The Human Microbiome Project has analysed the largest cohort and set of distinct, clinically relevant body habitats so far, finding the diversity and abundance of each habitat’s signature microbes to vary widely even among healthy subjects, with strong niche specialization both within and among individuals.
It is reported that high-grade serous ovarian cancer is characterized by TP53 mutations in almost all tumours (96%); low prevalence but statistically recurrent somatic mutations in nine further genes including NF1, BRCA1,BRCA2, RB1 and CDK12; 113 significant focal DNA copy number aberrations; and promoter methylation events involving 168 genes.
VarScan is presented, an open source tool for variant detection that is compatible with several short read aligners that demonstrates its ability to detect SNPs and indels with high sensitivity and specificity, in both Roche/454 sequencing of individuals and deep Illumina/Solexa sequencing of pooled samples.
Somatic mutations in primary lung adenocarcinoma for several tumour suppressor genes involved in other cancers and for sequence changes in PTPRD as well as the frequently deleted gene LRP1B are found.
The interim integrative analysis of DNA copy number, gene expression and DNA methylation aberrations in 206 glioblastomas reveals a link between MGMT promoter methylation and a hypermutator phenotype consequent to mismatch repair deficiency in treated gliobeasts, demonstrating that it can rapidly expand knowledge of the molecular basis of cancer.