The finished sequence of human chromosome 10 comprises a total of 131,666,441 base pairs. It represents 99.4% of the euchromatic DNA and includes one megabase of heterochromatic sequence within the pericentromeric region of the short and long arm of the chromosome. Sequence annotation revealed 1,357 genes, of which 816 are protein coding, and 430 are pseudogenes. We observed widespread occurrence of overlapping coding genes (either strand) and identified 67 antisense transcripts. Our analysis suggests that both inter- and intrachromosomal segmental duplications have impacted on the gene count on chromosome 10. Multispecies comparative analysis indicated that we can readily annotate the protein-coding genes with current resources. We estimate that over 95% of all coding exons were identified in this study. Assessment of single base changes between the human chromosome 10 and chimpanzee sequence revealed nonsense mutations in only 21 coding genes with respect to the human sequence.

Chromosome 6 is a metacentric chromosome that constitutes about 6% of the human genome. The finished sequence comprises 166,880,988 base pairs, representing the largest chromosome sequenced so far. The entire sequence has been subjected to high-quality manual annotation, resulting in the evidence-supported identification of 1,557 genes and 633 pseudogenes. Here we report that at least 96% of the protein-coding genes have been identified, as assessed by multi-species comparative sequence analysis, and provide evidence for the presence of further, otherwise unsupported exons/genes. Among these are genes directly implicated in cancer, schizophrenia, autoimmunity and many other diseases. Chromosome 6 harbours the largest transfer RNA gene cluster in the genome; we show that this cluster co-localizes with a region of high transcriptional activity. Within the essential immune loci of the major histocompatibility complex, we find HLA-B to be the most polymorphic gene on chromosome 6 and in the human genome.

Chromosome 13 is the largest acrocentric human chromosome. It carries genes involved in cancer including the breast cancer type 2 (BRCA2) and retinoblastoma (RB1) genes, is frequently rearranged in B-cell chronic lymphocytic leukaemia, and contains the DAOA locus associated with bipolar disorder and schizophrenia. We describe completion and analysis of 95.5 megabases (Mb) of sequence from chromosome 13, which contains 633 genes and 296 pseudogenes. We estimate that more than 95.4% of the protein-coding genes of this chromosome have been identified, on the basis of comparison with other vertebrate genome sequences. Additionally, 105 putative non-coding RNA genes were found. Chromosome 13 has one of the lowest gene densities (6.5 genes per Mb) among human chromosomes, and contains a central region of 38 Mb where the gene density drops to only 3.1 genes per Mb.

Chromosome 9 is highly structurally polymorphic. It contains the largest autosomal block of heterochromatin, which is heteromorphic in 6–8% of humans, whereas pericentric inversions occur in more than 1% of the population. The finished euchromatic sequence of chromosome 9 comprises 109,044,351 base pairs and represents >99.6% of the region. Analysis of the sequence reveals many intra- and interchromosomal duplications, including segmental duplications adjacent to both the centromere and the large heterochromatic block. We have annotated 1,149 genes, including genes implicated in male-to-female sex reversal, cancer and neurodegenerative disease, and 426 pseudogenes. The chromosome contains the largest interferon gene cluster in the human genome. There is also a region of exceptionally high gene and G + C content including genes paralogous to those in the major histocompatibility complex. We have also detected recently duplicated genes that exhibit different rates of sequence divergence, presumably reflecting natural selection.

Chromosome 6 is a metacentric chromosome that constitutes about 6% of the human genome. The finished sequence comprises 166,880,988 base pairs, representing the largest chromosome sequenced so far. The entire sequence has been subjected to high-quality manual annotation, resulting in the evidence-supported identification of 1,557 genes and 633 pseudogenes. Here we report that at least 96% of the protein-coding genes have been identified, as assessed by multi-species comparative sequence analysis, and provide evidence for the presence of further, otherwise unsupported exons/genes. Among these are genes directly implicated in cancer, schizophrenia, autoimmunity and many other diseases. Chromosome 6 harbours the largest transfer RNA gene cluster in the genome; we show that this cluster co-localizes with a region of high transcriptional activity. Within the essential immune loci of the major histocompatibility complex, we find HLA-B to be the most polymorphic gene on chromosome 6 and in the human genome.

Objective: To determine the best therapeutic regimen, using currently approved drugs, for treatment of relapsed cytomegalovirus (CMV) retinitis.Design: Multicenter, randomized, controlled clinical trial.Setting: Ophthalmology and acquired immunodeficiency syndrome (AIDS) services at tertiary care medical centers.Patients: Two hundred seventy-nine patients with AIDS and either persistently active or relapsed CMV retinitis.Intervention: Patients were randomized to one of three therapeutic regimens: induction with foscarnet sodium at 90 mg/kg intravenously every 12 hours for 2 weeks, followed by maintenance at a dosage of 120 mg/kg per day (foscar net group); induction with ganciclovir sodium at 5 mg/kg intravenously every 12 hours for 2 weeks followed by maintenance at 10 mg/kg per day (ganciclovir group); or continuation of previous maintenance therapy plus induction with the other drug (either ganciclovir or foscarnet) for 2 weeks followed by maintenance therapy with both drugs, ganciclovir sodium at 5 mg/kg per day and foscarnet sodium at 90 mg/kg per day (combination therapy group).Outcomes: Mortality, retinitis progression, visual acuity, visual fields, and morbidity.Results: The mortality rate was similar among the three groups. Median survival times were as follows: foscarnet group, 8.4 months; ganciclovir group, 9.0 months; and combination therapy group, 8.6 months (P=.89). Comparison of retinitis progression, as evaluated in a masked fashion by the centralized Fundus Photograph Reading Center (FPRC), revealed that combination therapy was the most effective regimen for controlling the retinitis. The median times to retinitis progression were as follows: foscarnet group, 1.3 months; ganciclovir group, 2.0 months; and combination therapy group, 4.3 months (P<.001). Although no difference could be detected in visual acuity outcomes, visual field loss and retinal area involvement on fundus photographs both paralleled the progression results, with the most favorable results in the combination therapy group. The rates of visual field loss were as follows: foscarnet group, 28 degrees per month; ganciclovir group, 18 degrees per month; combination therapy group, 16 degrees per month (P=.009), and the rates of increase of retinal area involved by CMV were as follows: foscarnet group, 2.47% per month; ganciclovir group, 1.40% per month; and combination therapy group, 1.19% per month (P=.04). While side effects were similar among the three treatment groups, combination therapy was associated with the greatest negative impact of treatment on quality-of-life measures.Conclusions: For patients with AIDS and CMV retinitis whose retinitis has relapsed and who can tolerate both drugs, combination therapy appears to be the most effective therapy for controlling CMV retinitis.