RESUMEN
The International Human Genome Sequencing Consortium (IHGSC) recently completed a sequence of the human genome. As part of this project, we have focused on chromosome 8. Although some chromosomes exhibit extreme characteristics in terms of length, gene content, repeat content and fraction segmentally duplicated, chromosome 8 is distinctly typical in character, being very close to the genome median in each of these aspects. This work describes a finished sequence and gene catalogue for the chromosome, which represents just over 5% of the euchromatic human genome. A unique feature of the chromosome is a vast region of approximately 15 megabases on distal 8p that appears to have a strikingly high mutation rate, which has accelerated in the hominids relative to other sequenced mammals. This fast-evolving region contains a number of genes related to innate immunity and the nervous system, including loci that appear to be under positive selection--these include the major defensin (DEF) gene cluster and MCPH1, a gene that may have contributed to the evolution of expanded brain size in the great apes. The data from chromosome 8 should allow a better understanding of both normal and disease biology and genome evolution.
Asunto(s)
Cromosomas Humanos Par 8/genética , Evolución Molecular , Animales , Mapeo Contig , ADN Satélite/genética , Defensinas/genética , Eucromatina/genética , Femenino , Humanos , Inmunidad Innata/genética , Masculino , Datos de Secuencia Molecular , Familia de Multigenes/genética , Análisis de Secuencia de ADNRESUMEN
Hydroxyapatite cement (BoneSource®) and brushite calcium phosphate cement (chronOS™ Inject) were tested for fixation of glass ceramic implants (Bioverit®) in experimentally created cranial defects in 24 adult New Zealand White rabbits. Aim of the in vivo study was to assess and compare the biocompatibility and osseointegration of the implanted materials. Macroscopic and histological evaluations were performed 1 month, 3 months, and 6 months postoperatively. All implanted materials were well tolerated by the surrounding tissue. Both bone cements exhibited osteoconductive properties. Differences could be detected regarding to the rates of cement resorption and new bone formation. The brushite cement was resorbed faster than the hydroxyapatite cement. The chronOS™ Inject samples exhibited a higher rate of connective tissue formation and an insufficient osseointegration. BoneSource® was replaced by bone with minimal invasion of connective tissue. New bone formation occurred faster compared to the chronOS™ Inject group. Bioverit® implants fixed with BoneSource® were successfully osseointegrated.
Asunto(s)
Cementos para Huesos , Regeneración Ósea , Cerámica , Hidroxiapatitas , Cráneo/cirugía , Animales , Materiales Biocompatibles , Cementos para Huesos/química , Sustitutos de Huesos/química , Fosfatos de Calcio/química , Cerámica/química , Femenino , Vidrio/química , Ensayo de Materiales , Modelos Animales , Oseointegración , ConejosRESUMEN
Careful manual annotation of the human reference sequence provides a solid basis for the identification of disease-associated genes. Toward this end, we focused on a medically relevant 2.6-Mb region of the human chromosome Xp11.4 between markers DXS9851 and DXS9751 and identified 16 transcription units according to the Vertebrate Genome Annotation (Vega) rules. In order to validate these annotations, we performed a comprehensive RT-PCR expression analysis and a human-mouse comparison. This revealed, despite the high overall genomic conservation of the region, remarkable differences of the gene content between human and mouse. Whereas 12 of 16 annotations were confirmed by RT-PCR in human tissues, for only seven genes mouse orthologs could be identified and found to be expressed. This indicates that a comprehensive and experimentally supported annotation effort of the human genome simultaneously highlights regions with striking differences in gene organization to other species and may indicate evolutionary events specific to the human lineage demanding further functional analyses.