RESUMEN
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.
Asunto(s)
Cromosomas Humanos Par 1/genética , Secuencia de Bases , Momento de Replicación del ADN , Enfermedad , Duplicación de Gen , Genes/genética , Variación Genética/genética , Genómica , Humanos , Datos de Secuencia Molecular , Sistemas de Lectura Abierta/genética , Seudogenes/genética , Recombinación Genética/genética , Selección Genética , Análisis de Secuencia de ADNRESUMEN
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.
Asunto(s)
Cromosomas Humanos Par 9/genética , Genes , Mapeo Físico de Cromosoma , Composición de Base , Eucromatina/genética , Evolución Molecular , Femenino , Duplicación de Gen , Genes Duplicados/genética , Variación Genética/genética , Genética Médica , Genómica , Heterocromatina/genética , Humanos , Masculino , Neoplasias/genética , Enfermedades Neurodegenerativas/genética , Seudogenes/genética , Análisis de Secuencia de ADN , Procesos de Determinación del SexoRESUMEN
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.
Asunto(s)
Cromosomas Humanos Par 10/genética , Genes , Mapeo Físico de Cromosoma , Animales , Composición de Base , Mapeo Contig , Islas de CpG/genética , Evolución Molecular , Exones/genética , Duplicación de Gen , Variación Genética/genética , Genética Médica , Genómica , Humanos , Pan troglodytes/genética , Proteínas/genética , Seudogenes/genética , Análisis de Secuencia de ADNRESUMEN
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.
Asunto(s)
Cromosomas Humanos Par 13/genética , Genes/genética , Mapeo Físico de Cromosoma , Mapeo Cromosómico , Genética Médica , Humanos , Seudogenes/genética , ARN no Traducido/genética , Análisis de Secuencia de ADNRESUMEN
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.
Asunto(s)
Cromosomas Humanos Par 6/genética , Genes/genética , Mapeo Físico de Cromosoma , Animales , Exones/genética , Enfermedades Genéticas Congénitas/genética , Antígenos HLA-B/genética , Humanos , Seudogenes/genética , ARN de Transferencia/genética , Análisis de Secuencia de ADNRESUMEN
The human genome holds an extraordinary trove of information about human development, physiology, medicine and evolution. Here we report the results of an international collaboration to produce and make freely available a draft sequence of the human genome. We also present an initial analysis of the data, describing some of the insights that can be gleaned from the sequence.
Asunto(s)
Genoma Humano , Proyecto Genoma Humano , Análisis de Secuencia de ADN , Animales , Mapeo Cromosómico , Secuencia Conservada , Islas de CpG , Elementos Transponibles de ADN , Bases de Datos Factuales , Industria Farmacéutica , Evolución Molecular , Predicción , Secuencia Rica en GC , Duplicación de Gen , Genes , Enfermedades Genéticas Congénitas , Genética Médica , Humanos , Mutación , Sector Privado , Proteínas/genética , Proteoma , Sector Público , ARN/genética , Secuencias Repetitivas de Ácidos Nucleicos , Análisis de Secuencia de ADN/métodos , Especificidad de la EspecieRESUMEN
The human genome sequence will provide a reference for measuring DNA sequence variation in human populations. Sequence variants are responsible for the genetic component of individuality, including complex characteristics such as disease susceptibility and drug response. Most sequence variants are single nucleotide polymorphisms (SNPs), where two alternate bases occur at one position. Comparison of any two genomes reveals around 1 SNP per kilobase. A sufficiently dense map of SNPs would allow the detection of sequence variants responsible for particular characteristics on the basis that they are associated with a specific SNP allele. Here we have evaluated large-scale sequencing approaches to obtaining SNPs, and have constructed a map of 2,730 SNPs on human chromosome 22. Most of the SNPs are within 25 kilobases of a transcribed exon, and are valuable for association studies. We have scaled up the process, detecting over 65,000 SNPs in the genome as part of The SNP Consortium programme, which is on target to build a map of 1 SNP every 5 kilobases that is integrated with the human genome sequence and that is freely available in the public domain.
Asunto(s)
Cromosomas Humanos Par 22 , Polimorfismo de Nucleótido Simple , Análisis de Secuencia de ADN/métodos , Línea Celular , Mapeo Cromosómico/métodos , Estudios de Evaluación como Asunto , Biblioteca de Genes , Genoma Humano , Humanos , Alineación de SecuenciaRESUMEN
Knowledge of the complete genomic DNA sequence of an organism allows a systematic approach to defining its genetic components. The genomic sequence provides access to the complete structures of all genes, including those without known function, their control elements, and, by inference, the proteins they encode, as well as all other biologically important sequences. Furthermore, the sequence is a rich and permanent source of information for the design of further biological studies of the organism and for the study of evolution through cross-species sequence comparison. The power of this approach has been amply demonstrated by the determination of the sequences of a number of microbial and model organisms. The next step is to obtain the complete sequence of the entire human genome. Here we report the sequence of the euchromatic part of human chromosome 22. The sequence obtained consists of 12 contiguous segments spanning 33.4 megabases, contains at least 545 genes and 134 pseudogenes, and provides the first view of the complex chromosomal landscapes that will be found in the rest of the genome.
Asunto(s)
Cromosomas Humanos Par 22 , Proyecto Genoma Humano , Análisis de Secuencia de ADN , Animales , Mapeo Cromosómico/métodos , ADN , Dosificación de Gen , Humanos , Ratones , Datos de Secuencia Molecular , Secuencias Repetitivas de Ácidos Nucleicos , Especificidad de la EspecieRESUMEN
As part of our effort to sequence the 100-megabase (Mb) genome of the nematode Caenorhabditis elegans, we have completed the nucleotide sequence of a contiguous 2,181,032 base pairs in the central gene cluster of chromosome III. Analysis of the finished sequence has indicated an average density of about one gene per five kilobases; comparison with the public sequence databases reveals similarities to previously known genes for about one gene in three. In addition, the genomic sequence contains several intriguing features, including putative gene duplications and a variety of other repeats with potential evolutionary implications.