RESUMO
As the final sequencing of the human genome has now been completed, we present the results of the largest examination of the quality of the finished DNA sequence. The completed study covers the major contributing sequencing centres and is based on a rigorous combination of laboratory experiments and computational analysis.
Assuntos
Biologia Computacional/normas , Genoma Humano , Projeto Genoma Humano , Análise de Sequência de DNA/normas , Pareamento de Bases , Biologia Computacional/tendências , Humanos , Controle de Qualidade , Projetos de Pesquisa , Sensibilidade e Especificidade , Análise de Sequência de DNA/tendênciasRESUMO
Human chromosome 16 features one of the highest levels of segmentally duplicated sequence among the human autosomes. We report here the 78,884,754 base pairs of finished chromosome 16 sequence, representing over 99.9% of its euchromatin. Manual annotation revealed 880 protein-coding genes confirmed by 1,670 aligned transcripts, 19 transfer RNA genes, 341 pseudogenes and three RNA pseudogenes. These genes include metallothionein, cadherin and iroquois gene families, as well as the disease genes for polycystic kidney disease and acute myelomonocytic leukaemia. Several large-scale structural polymorphisms spanning hundreds of kilobase pairs were identified and result in gene content differences among humans. Whereas the segmental duplications of chromosome 16 are enriched in the relatively gene-poor pericentromere of the p arm, some are involved in recent gene duplication and conversion events that are likely to have had an impact on the evolution of primates and human disease susceptibility.
Assuntos
Cromossomos Humanos Par 16/genética , Duplicação Gênica , Mapeamento Físico do Cromossomo , Animais , Genes/genética , Genômica , Heterocromatina/genética , Humanos , Dados de Sequência Molecular , Polimorfismo Genético/genética , Análise de Sequência de DNA , Sintenia/genéticaRESUMO
Chromosome 5 is one of the largest human chromosomes and contains numerous intrachromosomal duplications, yet it has one of the lowest gene densities. This is partially explained by numerous gene-poor regions that display a remarkable degree of noncoding conservation with non-mammalian vertebrates, suggesting that they are functionally constrained. In total, we compiled 177.7 million base pairs of highly accurate finished sequence containing 923 manually curated protein-coding genes including the protocadherin and interleukin gene families. We also completely sequenced versions of the large chromosome-5-specific internal duplications. These duplications are very recent evolutionary events and probably have a mechanistic role in human physiological variation, as deletions in these regions are the cause of debilitating disorders including spinal muscular atrophy.
Assuntos
Cromossomos Humanos Par 5/genética , Análise de Sequência de DNA , Animais , Composição de Bases , Caderinas/genética , Sequência Conservada/genética , Duplicação Gênica , Genes/genética , Doenças Genéticas Inatas/genética , Genômica , Humanos , Interleucinas/genética , Dados de Sequência Molecular , Atrofia Muscular Espinal/genética , Pan troglodytes/genética , Mapeamento Físico do Cromossomo , Pseudogenes/genética , Sintenia/genética , Vertebrados/genéticaRESUMO
Chromosome 19 has the highest gene density of all human chromosomes, more than double the genome-wide average. The large clustered gene families, corresponding high G + C content, CpG islands and density of repetitive DNA indicate a chromosome rich in biological and evolutionary significance. Here we describe 55.8 million base pairs of highly accurate finished sequence representing 99.9% of the euchromatin portion of the chromosome. Manual curation of gene loci reveals 1,461 protein-coding genes and 321 pseudogenes. Among these are genes directly implicated in mendelian disorders, including familial hypercholesterolaemia and insulin-resistant diabetes. Nearly one-quarter of these genes belong to tandemly arranged families, encompassing more than 25% of the chromosome. Comparative analyses show a fascinating picture of conservation and divergence, revealing large blocks of gene orthology with rodents, scattered regions with more recent gene family expansions and deletions, and segments of coding and non-coding conservation with the distant fish species Takifugu.