RESUMO
Human chromosome 2 is unique to the human lineage in being the product of a head-to-head fusion of two intermediate-sized ancestral chromosomes. Chromosome 4 has received attention primarily related to the search for the Huntington's disease gene, but also for genes associated with Wolf-Hirschhorn syndrome, polycystic kidney disease and a form of muscular dystrophy. Here we present approximately 237 million base pairs of sequence for chromosome 2, and 186 million base pairs for chromosome 4, representing more than 99.6% of their euchromatic sequences. Our initial analyses have identified 1,346 protein-coding genes and 1,239 pseudogenes on chromosome 2, and 796 protein-coding genes and 778 pseudogenes on chromosome 4. Extensive analyses confirm the underlying construction of the sequence, and expand our understanding of the structure and evolution of mammalian chromosomes, including gene deserts, segmental duplications and highly variant regions.
Assuntos
Cromossomos Humanos Par 2/genética , Cromossomos Humanos Par 4/genética , Animais , Composição de Bases , Sequência de Bases , Centrômero/genética , Sequência Conservada/genética , Ilhas de CpG/genética , Eucromatina/genética , Etiquetas de Sequências Expressas , Duplicação Gênica , Variação Genética/genética , Genômica , Humanos , Dados de Sequência Molecular , Mapeamento Físico do Cromossomo , Polimorfismo Genético/genética , Primatas/genética , Proteínas/genética , Pseudogenes/genética , RNA Mensageiro/análise , RNA Mensageiro/genética , RNA não Traduzido/análise , RNA não Traduzido/genética , Recombinação Genética/genética , Análise de Sequência de DNARESUMO
Strategies for assembling large, complex genomes have evolved to include a combination of whole-genome shotgun sequencing and hierarchal map-assisted sequencing. Whole-genome maps of all types can aid genome assemblies, generally starting with low-resolution cytogenetic maps and ending with the highest resolution of sequence. Fingerprint clone maps are based upon complete restriction enzyme digests of clones representative of the target genome, and ultimately comprise a near-contiguous path of clones across the genome. Such clone-based maps are used to validate sequence assembly order, supply long-range linking information for assembled sequences, anchor sequences to the genetic map and provide templates for closing gaps. Fingerprint maps are also a critical resource for subsequent functional genomic studies, because they provide a redundant and ordered sampling of the genome with clones. In an accompanying paper we describe the draft genome sequence of the chicken, Gallus gallus, the first species sequenced that is both a model organism and a global food source. Here we present a clone-based physical map of the chicken genome at 20-fold coverage, containing 260 contigs of overlapping clones. This map represents approximately 91% of the chicken genome and enables identification of chicken clones aligned to positions in other sequenced genomes.
Assuntos
Galinhas/genética , Genoma , Genômica , Mapeamento Físico do Cromossomo , Animais , Cromossomos Artificiais Bacterianos/genética , Clonagem Molecular , Mapeamento de Sequências Contíguas , Impressões Digitais de DNA , Ligação Genética/genética , Sitios de Sequências RotuladasRESUMO
As part of the effort to sequence the genome of Rattus norvegicus, we constructed a physical map comprised of fingerprinted bacterial artificial chromosome (BAC) clones from the CHORI-230 BAC library. These BAC clones provide approximately 13-fold redundant coverage of the genome and have been assembled into 376 fingerprint contigs. A yeast artificial chromosome (YAC) map was also constructed and aligned with the BAC map via fingerprinted BAC and P1 artificial chromosome clones (PACs) sharing interspersed repetitive sequence markers with the YAC-based physical map. We have annotated 95% of the fingerprint map clones in contigs with coordinates on the version 3.1 rat genome sequence assembly, using BAC-end sequences and in silico mapping methods. These coordinates have allowed anchoring 358 of the 376 fingerprint map contigs onto the sequence assembly. Of these, 324 contigs are anchored to rat genome sequences localized to chromosomes, and 34 contigs are anchored to unlocalized portions of the rat sequence assembly. The remaining 18 contigs, containing 54 clones, still require placement. The fingerprint map is a high-resolution integrative data resource that provides genome-ordered associations among BAC, YAC, and PAC clones and the assembled sequence of the rat genome.
Assuntos
Cromossomos Artificiais Bacterianos/genética , Cromossomos Artificiais de Levedura/genética , Genoma , Mapeamento Físico do Cromossomo/métodos , Animais , Automação , Cromossomos/genética , Clonagem Molecular/métodos , Biologia Computacional/métodos , Biologia Computacional/normas , Mapeamento de Sequências Contíguas/métodos , Mapeamento de Sequências Contíguas/normas , Impressões Digitais de DNA/métodos , Impressões Digitais de DNA/normas , Marcadores Genéticos/genética , Mapeamento Físico do Cromossomo/normas , Reação em Cadeia da Polimerase/métodos , Ratos , Análise de Sequência de DNA/métodos , Análise de Sequência de DNA/normasRESUMO
A physical map of a genome is an essential guide for navigation, allowing the location of any gene or other landmark in the chromosomal DNA. We have constructed a physical map of the mouse genome that contains 296 contigs of overlapping bacterial clones and 16,992 unique markers. The mouse contigs were aligned to the human genome sequence on the basis of 51,486 homology matches, thus enabling use of the conserved synteny (correspondence between chromosome blocks) of the two genomes to accelerate construction of the mouse map. The map provides a framework for assembly of whole-genome shotgun sequence data, and a tile path of clones for generation of the reference sequence. Definition of the human-mouse alignment at this level of resolution enables identification of a mouse clone that corresponds to almost any position in the human genome. The human sequence may be used to facilitate construction of other mammalian genome maps using the same strategy.