RESUMO
The reference sequence for each human chromosome provides the framework for understanding genome function, variation and evolution. Here we report the finished sequence and biological annotation of human chromosome 1. Chromosome 1 is gene-dense, with 3,141 genes and 991 pseudogenes, and many coding sequences overlap. Rearrangements and mutations of chromosome 1 are prevalent in cancer and many other diseases. Patterns of sequence variation reveal signals of recent selection in specific genes that may contribute to human fitness, and also in regions where no function is evident. Fine-scale recombination occurs in hotspots of varying intensity along the sequence, and is enriched near genes. These and other studies of human biology and disease encoded within chromosome 1 are made possible with the highly accurate annotated sequence, as part of the completed set of chromosome sequences that comprise the reference human genome.
Assuntos
Cromossomos Humanos Par 1/genética , Sequência de Bases , Período de Replicação do DNA , Doença , Duplicação Gênica , Genes/genética , Variação Genética/genética , Genômica , Humanos , Dados de Sequência Molecular , Fases de Leitura Aberta/genética , Pseudogenes/genética , Recombinação Genética/genética , Seleção Genética , Análise de Sequência de DNARESUMO
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.
Assuntos
Cromossomos Humanos Par 9/genética , Genes , Mapeamento Físico do Cromossomo , Composição de Bases , Eucromatina/genética , Evolução Molecular , Feminino , Duplicação Gênica , Genes Duplicados/genética , Variação Genética/genética , Genética Médica , Genômica , Heterocromatina/genética , Humanos , Masculino , Neoplasias/genética , Doenças Neurodegenerativas/genética , Pseudogenes/genética , Análise de Sequência de DNA , Processos de Determinação SexualRESUMO
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.
Assuntos
Cromossomos Humanos Par 6/genética , Genes/genética , Mapeamento Físico do Cromossomo , Animais , Éxons/genética , Doenças Genéticas Inatas/genética , Antígenos HLA-B/genética , Humanos , Pseudogenes/genética , RNA de Transferência/genética , Análise de Sequência de DNARESUMO
The finished sequence of human chromosome 20 comprises 59,187,298 base pairs (bp) and represents 99.4% of the euchromatic DNA. A single contig of 26 megabases (Mb) spans the entire short arm, and five contigs separated by gaps totalling 320 kb span the long arm of this metacentric chromosome. An additional 234,339 bp of sequence has been determined within the pericentromeric region of the long arm. We annotated 727 genes and 168 pseudogenes in the sequence. About 64% of these genes have a 5' and a 3' untranslated region and a complete open reading frame. Comparative analysis of the sequence of chromosome 20 to whole-genome shotgun-sequence data of two other vertebrates, the mouse Mus musculus and the puffer fish Tetraodon nigroviridis, provides an independent measure of the efficiency of gene annotation, and indicates that this analysis may account for more than 95% of all coding exons and almost all genes.
Assuntos
Cromossomos Humanos Par 20 , Animais , Sequência de Bases , Biologia Computacional , Mapeamento de Sequências Contíguas , DNA , Doenças Genéticas Inatas/genética , Variação Genética , Humanos , Camundongos , Mapeamento Físico do Cromossomo , Proteoma , Análise de Sequência de DNARESUMO
We report the case of a patient who has a 23-year history of endometrial stromal sarcoma (ESS). She initially underwent tumor-reductive surgery followed by adjuvant radiotherapy. The pelvic tumor recurred nearly 8 years later, obstructing the ureter and directly invading the bladder. It propagated into the vena cava as a thrombus and finally spread into the right heart chambers, leading to cardiac failure 13 years after the recurrence. The patient was treated with hormonal therapy, multiple resections of the pelvic tumor, chemoembolization, and systemic chemotherapy with doxorubicin and cyclophosphamide. She developed recurrent intractable symptoms and was started on prolonged oral etoposide therapy, which stabilized the size of the pelvic tumor and relieved her symptoms for 3 years. Her quality of life has markedly improved without significant morbidity. We review the options for treating recurrent ESS and suggest that use of prolonged oral etoposide therapy warrants further study in this setting.
Assuntos
Neoplasias do Endométrio/tratamento farmacológico , Etoposídeo/administração & dosagem , Sarcoma do Estroma Endometrial/tratamento farmacológico , Administração Oral , Terapia Combinada , Esquema de Medicação , Neoplasias do Endométrio/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Terapia de Salvação , Sarcoma do Estroma Endometrial/cirurgiaRESUMO
The efficacy and side effects of subcutaneous epinephrine (E) and aerosolized metaproterenol (M) were compared in acute asthma. Adults randomly received E 0.3 mg sub-Q q20min (max 0.9 mg; n = 20) or M 15 mg in 3.0 ml NaCl 0.9% nebulized over 10 minutes (n = 20) in a double-blind fashion. Vital signs and peak expiratory flow rate (PEFR) were measured every ten minutes for one hour. The two groups were comparable in age, weight, baseline theophylline concentration, PEFR, heart rate, and systolic and diastolic blood pressure. PEFR improved in both groups within ten minutes (p less than 0.01; analysis of variance). There was no difference in PEFR between the groups over the one-hour observation period following treatment. Heart rate decreased following treatment in M patients (p less than 0.05), but remained unchanged in E patients. Systolic blood pressure rose slightly in E patients (p less than 0.01), but remained unchanged in M patients. Subcutaneous E and nebulized M are equally effective as initial therapy in acute asthma.
