A 2.91-billion base pair (bp) consensus sequence of the euchromatic portion of the human genome was generated by the whole-genome shotgun sequencing method. The 14.8-billion bp DNA sequence was generated over 9 months from 27,271,853 high-quality sequence reads (5.11-fold coverage of the genome) from both ends of plasmid clones made from the DNA of five individuals. Two assembly strategies—a whole-genome assembly and a regional chromosome assembly—were used, each combining sequence data from Celera and the publicly funded genome effort. The public data were shredded into 550-bp segments to create a 2.9-fold coverage of those genome regions that had been sequenced, without including biases inherent in the cloning and assembly procedure used by the publicly funded group. This brought the effective coverage in the assemblies to eightfold, reducing the number and size of gaps in the final assembly over what would be obtained with 5.11-fold coverage. The two assembly strategies yielded very similar results that largely agree with independent mapping data. The assemblies effectively cover the euchromatic regions of the human chromosomes. More than 90% of the genome is in scaffold assemblies of 100,000 bp or more, and 25% of the genome is in scaffolds of 10 million bp or larger. Analysis of the genome sequence revealed 26,588 protein-encoding transcripts for which there was strong corroborating evidence and an additional ∼12,000 computationally derived genes with mouse matches or other weak supporting evidence. Although gene-dense clusters are obvious, almost half the genes are dispersed in low G+C sequence separated by large tracts of apparently noncoding sequence. Only 1.1% of the genome is spanned by exons, whereas 24% is in introns, with 75% of the genome being intergenic DNA. Duplications of segmental blocks, ranging in size up to chromosomal lengths, are abundant throughout the genome and reveal a complex evolutionary history. Comparative genomic analysis indicates vertebrate expansions of genes associated with neuronal function, with tissue-specific developmental regulation, and with the hemostasis and immune systems. DNA sequence comparisons between the consensus sequence and publicly funded genome data provided locations of 2.1 million single-nucleotide polymorphisms (SNPs). A random pair of human haploid genomes differed at a rate of 1 bp per 1250 on average, but there was marked heterogeneity in the level of polymorphism across the genome. Less than 1% of all SNPs resulted in variation in proteins, but the task of determining which SNPs have functional consequences remains an open challenge.

Anopheles gambiae is the principal vector of malaria, a disease that afflicts more than 500 million people and causes more than 1 million deaths each year. Tenfold shotgun sequence coverage was obtained from the PEST strain of A. gambiae and assembled into scaffolds that span 278 million base pairs. A total of 91% of the genome was organized in 303 scaffolds; the largest scaffold was 23.1 million base pairs. There was substantial genetic variation within this strain, and the apparent existence of two haplotypes of approximately equal frequency (“dual haplotypes”) in a substantial fraction of the genome likely reflects the outbred nature of the PEST strain. The sequence produced a conservative inference of more than 400,000 single-nucleotide polymorphisms that showed a markedly bimodal density distribution. Analysis of the genome sequence revealed strong evidence for about 14,000 protein-encoding transcripts. Prominent expansions in specific families of proteins likely involved in cell adhesion and immunity were noted. An expressed sequence tag analysis of genes regulated by blood feeding provided insights into the physiological adaptations of a hematophagous insect.

Background: Most eukaryotic genomes include a substantial repeat-rich fraction termed heterochromatin, which is concentrated in centric and telomeric regions. The repetitive nature of heterochromatic sequence makes it difficult to assemble and analyze. To better understand the heterochromatic component of the Drosophila melanogaster genome, we characterized and annotated portions of a whole-genome shotgun sequence assembly.

The high degree of similarity between the mouse and human genomes is demonstrated through analysis of the sequence of mouse chromosome 16 (Mmu 16), which was obtained as part of a whole-genome shotgun assembly of the mouse genome. The mouse genome is about 10% smaller than the human genome, owing to a lower repetitive DNA content. Comparison of the structure and protein-coding potential of Mmu 16 with that of the homologous segments of the human genome identifies regions of conserved synteny with human chromosomes (Hsa) 3, 8, 12, 16, 21, and 22. Gene content and order are highly conserved between Mmu 16 and the syntenic blocks of the human genome. Of the 731 predicted genes on Mmu 16, 509 align with orthologs on the corresponding portions of the human genome, 44 are likely paralogous to these genes, and 164 genes have homologs elsewhere in the human genome; there are 14 genes for which we could find no human counterpart.

Objective This review updates the 1998 International Society for Peritoneal Dialysis (ISPD) recommendations for peritoneal dialysis catheters and exit-site practices (Gokal R, et al. Peritoneal catheters and exit-site practices toward optimum peritoneal access: 1998 update. Perit Dial Int 1998; 18:11–33.) Design Data Sources: The Ovid and PubMed search engines were used to review the Medline databases of January 1980 through June 2003. Searches were restricted to human data; primary key word searches included dialysis, peritoneal dialysis, and continuous ambulatory peritoneal dialysis cross referenced with access, catheter, dialysis catheter, peritoneal dialysis catheter, and Tenckhoff catheter. Related searches were provided via the PubMed related articles link. Study Selection: Reports were selected if they provided identifiable information on catheter design, catheter placement technique, and survival or placement complications. Reports without such data were excluded from review. Each study was then categorized by its characteristics: single-center or multicenter; retrospective or prospective; controlled trial, with or without random patient assignment; or review article. Main Results There are few randomized controlled evaluations testing how catheter design and/or placement influence long-term survival and function, and these are typically conducted at a single center. The majority of reports represent retrospective single-center experiences, and these are supplemented by occasional multicenter data registries. Conclusions There is substantial variability in catheter outcomes between centers, and this variability is more closely correlated with operator and center characteristics than with catheter design. Some catheter designs appear to impact long-term catheter success, and, in some cases, specific patient characteristics and dialysis formats combine with specific catheter designs to influence catheter survival. Most reporters prefer two-cuff designs and placement of the deep cuff at an intramuscular location. Intramuscular cuff placement results in fewer pericatheter leaks and hernias, but makes catheter removal more difficult. High-risk patients (those with previous pelvic surgery) benefit from visual inspection of the peritoneum during catheter placement, and in randomized controlled trials, catheters with pre-shaped arcuate subcutaneous segments (“swan neck” designs) reduce the risk of early drainage failure via “migration.”