RESUMEN
After the completion of a draft human genome sequence, the International Human Genome Sequencing Consortium has proceeded to finish and annotate each of the 24 chromosomes comprising the human genome. Here we describe the sequencing and analysis of human chromosome 3, one of the largest human chromosomes. Chromosome 3 comprises just four contigs, one of which currently represents the longest unbroken stretch of finished DNA sequence known so far. The chromosome is remarkable in having the lowest rate of segmental duplication in the genome. It also includes a chemokine receptor gene cluster as well as numerous loci involved in multiple human cancers such as the gene encoding FHIT, which contains the most common constitutive fragile site in the genome, FRA3B. Using genomic sequence from chimpanzee and rhesus macaque, we were able to characterize the breakpoints defining a large pericentric inversion that occurred some time after the split of Homininae from Ponginae, and propose an evolutionary history of the inversion.
Asunto(s)
Cromosomas Humanos Par 3/genética , Animales , Secuencia de Bases , Rotura Cromosómica/genética , Inversión Cromosómica/genética , Mapeo Contig , Islas de CpG/genética , ADN Complementario/genética , Evolución Molecular , Etiquetas de Secuencia Expresada , Proyecto Genoma Humano , Humanos , Macaca mulatta/genética , Datos de Secuencia Molecular , Pan troglodytes/genética , Análisis de Secuencia de ADN , Sintenía/genéticaRESUMEN
Human chromosome 12 contains more than 1,400 coding genes and 487 loci that have been directly implicated in human disease. The q arm of chromosome 12 contains one of the largest blocks of linkage disequilibrium found in the human genome. Here we present the finished sequence of human chromosome 12, which has been finished to high quality and spans approximately 132 megabases, representing approximately 4.5% of the human genome. Alignment of the human chromosome 12 sequence across vertebrates reveals the origin of individual segments in chicken, and a unique history of rearrangement through rodent and primate lineages. The rate of base substitutions in recent evolutionary history shows an overall slowing in hominids compared with primates and rodents.
Asunto(s)
Cromosomas Humanos Par 12/genética , Animales , Composición de Base , Islas de CpG/genética , Evolución Molecular , Etiquetas de Secuencia Expresada , Genes/genética , Humanos , Desequilibrio de Ligamiento/genética , Repeticiones de Microsatélite/genética , Datos de Secuencia Molecular , Mutagénesis Insercional/genética , Pan troglodytes/genética , Análisis de Secuencia de ADN , Eliminación de Secuencia/genética , Elementos de Nucleótido Esparcido Corto/genética , Sintenía/genéticaRESUMEN
The human X chromosome has a unique biology that was shaped by its evolution as the sex chromosome shared by males and females. We have determined 99.3% of the euchromatic sequence of the X chromosome. Our analysis illustrates the autosomal origin of the mammalian sex chromosomes, the stepwise process that led to the progressive loss of recombination between X and Y, and the extent of subsequent degradation of the Y chromosome. LINE1 repeat elements cover one-third of the X chromosome, with a distribution that is consistent with their proposed role as way stations in the process of X-chromosome inactivation. We found 1,098 genes in the sequence, of which 99 encode proteins expressed in testis and in various tumour types. A disproportionately high number of mendelian diseases are documented for the X chromosome. Of this number, 168 have been explained by mutations in 113 X-linked genes, which in many cases were characterized with the aid of the DNA sequence.
Asunto(s)
Cromosomas Humanos X/genética , Evolución Molecular , Genómica , Análisis de Secuencia de ADN , Animales , Antígenos de Neoplasias/genética , Centrómero/genética , Cromosomas Humanos Y/genética , Mapeo Contig , Intercambio Genético/genética , Compensación de Dosificación (Genética) , Femenino , Ligamiento Genético/genética , Genética Médica , Humanos , Masculino , Polimorfismo de Nucleótido Simple/genética , ARN/genética , Secuencias Repetitivas de Ácidos Nucleicos/genética , Homología de Secuencia de Ácido Nucleico , Testículo/metabolismoRESUMEN
Pooled genomic indexing (PGI) is a method for mapping collections of bacterial artificial chromosome (BAC) clones between species by using a combination of clone pooling and DNA sequencing. PGI has been used to map a total of 3858 BAC clones covering approximately 24% of the rhesus macaque (Macaca mulatta) genome onto 4178 homologous loci in the human genome. A number of intrachromosomal rearrangements were detected by mapping multiple segments within the individual rhesus BACs onto multiple disjoined loci in the human genome. Transversal pooling designs involving shuffled BAC arrays were employed for robust mapping even with modest DNA sequence read coverage. A further innovation, short-tag pooled genomic indexing (ST-PGI), was also introduced to further improve the economy of mapping by sequencing multiple, short, mapable tags within a single sequencing reaction.