The systematic comparison of genomic sequences from different organisms represents a central focus of contemporary genome analysis. Comparative analyses of vertebrate sequences can identify coding and conserved non-coding regions, including regulatory elements, and provide insight into the forces that have rendered modern-day genomes. As a complement to whole-genome sequencing efforts, we are sequencing and comparing targeted genomic regions in multiple, evolutionarily diverse vertebrates. Here we report the generation and analysis of over 12 megabases (Mb) of sequence from 12 species, all derived from the genomic region orthologous to a segment of about 1.8 Mb on human chromosome 7 containing ten genes, including the gene mutated in cystic fibrosis. These sequences show conservation reflecting both functional constraints and the neutral mutational events that shaped this genomic region. In particular, we identify substantial numbers of conserved non-coding segments beyond those previously identified experimentally, most of which are not detectable by pair-wise sequence comparisons alone. Analysis of transposable element insertions highlights the variation in genome dynamics among these species and confirms the placement of rodents as a sister group to the primates.

Peritoneal membrane solute transport in peritoneal dialysis (PD) patients is assessed by the peritoneal equilibration test, which measures the ratio of creatinine in the dialysate to plasma after a standardized 4-h dwell (D/P c ). Patients then are classified as high, high-average, low-average, or low transporters on the basis of this result. A meta-analysis of observational studies was carried out to characterize the relationship between D/P c and mortality and technique failure in patients who are on PD. Citations were identified in Medline by using a combination of Medical Subject Heading search terms and key words related to PD, peritoneal membrane permeability/transport, and mortality and technique failure. The table of contents of relevant journals and bibliographies of relevant citations were reviewed in duplicate. Twenty studies that met study criteria were identified. Nineteen studies were pooled to generate a summary mortality relative risk of 1.15 for every 0.1 increase in the D/P c (95% confidence interval 1.07 to 1.23; P < 001). This result equated to an increased mortality risk of 21.9, 45.7, and 77.3% in low-average, high-average, and high transporters, respectively, as compared with patients with low transport status. Meta-regression analysis showed that the proportion of patients who were on continuous cycler PD within a study was inversely proportional to the mortality risk (P ‫؍‬ 0.05). The pooled summary relative risk for death-censored technique failure was 1.18 (95% confidence interval 0.96 to 1.46; P ‫؍‬ 0.12) for every 0.1 increase in the D/P c . This meta-analysis demonstrates that a higher peritoneal membrane solute transport rate is associated with a higher mortality risk and a trend to higher technique failure.J Am Soc Nephrol 17: 2591 -2598, 2006 . doi: 10.1681 P atients with ESRD, including those who are on peritoneal dialysis (PD), are at a much higher risk for premature death than the general population. Well-accepted risk factors for early mortality that have been identified in the PD population include age, diabetes, preexisting cardiovascular disease, and malnutrition/hypoalbuminemia (1-6).The peritoneal equilibration test (PET) characterizes the peritoneal membrane transport properties by determining the ratio of the creatinine concentration in the dialysate to that in the plasma after a 4-h dwell (D/P c ) and has been shown to vary considerably among individuals (7). Patients with a greater rate of membrane solute transport (i.e., higher D/P c ) will tend to have enhanced clearance of small solutes, including urea and creatinine, during shorter dwells. However, these patients will have greater peritoneal losses of protein, will be more prone to fluid retention as a result of rapid reabsorption of glucose from the dialysate and subsequent ultrafiltration dysfunction, and will have greater systemic exposure to glucose. These differences may have competing effects on both patient and technique survival such that from a biologic basis, it is unclear what, if any, the effect of pe...

The genome of the flowering plant Arabidopsis thaliana has five chromosomes. Here we report the sequence of the largest, chromosome 1, in two contigs of around 14.2 and 14.6 megabases. The contigs extend from the telomeres to the centromeric borders, regions rich in transposons, retrotransposons and repetitive elements such as the 180-base-pair repeat. The chromosome represents 25% of the genome and contains about 6,850 open reading frames, 236 transfer RNAs (tRNAs) and 12 small nuclear RNAs. There are two clusters of tRNA genes at different places on the chromosome. One consists of 27 tRNA(Pro) genes and the other contains 27 tandem repeats of tRNA(Tyr)-tRNA(Tyr)-tRNA(Ser) genes. Chromosome 1 contains about 300 gene families with clustered duplications. There are also many repeat elements, representing 8% of the sequence.

Although the cost of generating draft-quality genomic sequence continues to decline, refining that sequence by the process of "sequence finishing" remains expensive. Near-perfect finished sequence is an appropriate goal for the human genome and a small set of reference genomes; however, such a high-quality product cannot be cost-justified for large numbers of additional genomes, at least for the foreseeable future. Here we describe the generation and quality of an intermediate grade of finished genomic sequence (termed comparative-grade finished sequence), which is tailored for use in multispecies sequence comparisons. Our analyses indicate that this sequence is very high quality (with the residual gaps and errors mostly falling within repetitive elements) and reflects 99% of the total sequence. Importantly, comparative-grade sequence finishing requires ∼40-fold less reagents and ∼10-fold less personnel effort compared to the generation of near-perfect finished sequence, such as that produced for the human genome. Although applied here to finishing sequence derived from individual bacterial artificial chromosome (BAC) clones, one could envision establishing routines for refining sequences emanating from whole-genome shotgun sequencing projects to a similar quality level. Our experience to date demonstrates that comparative-grade sequence finishing represents a practical and affordable option for sequence refinement en route to comparative analyses.

The radial artery (RA) pressure waveform is commonly used to reconstruct the central aortic pressure waveform. Because the RA pressure waveform has been used as input to this process, its features that are dependent on the local arterial properties can influence the final reconstructed aortic waveform. In this study, we determined the effects of altered upper limb pulse wave velocity (PWV) and local wave reflection parameters on RA pressure waveform augmentation (RA-AIx). Twenty healthy volunteers (10 men) between the ages of 18 and 35 years of age were recruited. Simultaneous pressure waveforms were acquired using arterial tonometers from the right carotid and the radial arteries, prior to and following tourniquet induced hyperemia. The phase velocities from the pressure wave transfer function were used to estimate the pulse wave velocity (PWV(infinity)), the local reflection coefficient (Gamma) and an estimate of the terminal impedance of the upper limbs, PWV(0+). The RA-AIx was represented as a linear, three-parameter model that included the input (the AIx of the carotid artery pressure waveform, CA-AIx), the Gamma and PWV(infinity) of the arm. Tourniquet induced hyperemia did not alter Gamma but reduced PWV(infinity), and PWV(0+) and increased RA-AIx. Multiple linear regression analysis indicated that RA-AIx was increased by high levels of CA-AIx and PWV(infinity) and decreased by elevated Gamma. The relative weighing of CA-AIx, Gamma and PWV(infinity) on RA-AIx were 3:2:1, respectively. The AIx of RA is determined to an equal extent by the input and local factors. Interpretation of the AIx of the RA and the reconstructed central aortic waveform should be made in the context of this relationship.