Some of this increased gene number is likely to be a consequence of the TSD.Ī direct comparison of the zebrafish and human protein-coding genes reveals a number of interesting features. Zebrafish possess 26,206 protein-coding genes 6, more than any previously sequenced vertebrate, and they have a higher number of species-specific genes in their genome than do human, mouse or chicken. Gene duplicates that result from this process are called ohnologues (after Susumu Ohno who suggested this mechanism of gene duplication) 13. Compared to other vertebrate species, this ancestor underwent an additional round of whole-genome duplication (WGD) called the teleost-specific genome duplication (TSD) 12. Zebrafish are members of the teleostei infraclass, a monophyletic group that is thought to have arisen approximately 340 million years ago from a common ancestor 11. The clone and WGS sequence is tied to a high-resolution, high-density meiotic map called the Sanger AB Tübingen map (SATmap), named after the strains of zebrafish used to make the map ( Supplementary Information). The Zv9 assembly is a hybrid of high-quality finished clone sequence (83%) and whole-genome shotgun (WGS) sequence (17%), with a total size of 1.412 gigabases (Gb) ( Table 1). Our strategy resembled the clone-by-clone sequencing approach adopted previously for both the human and mouse genome projects. We chose Tübingen as the zebrafish reference strain as it had been used extensively to identify mutations affecting embryogenesis 2. The zebrafish genome-sequencing project was initiated at the Wellcome Trust Sanger Institute in 2001. Essential to this enterprise is a high-quality genome sequence and complete annotation of zebrafish protein-coding genes with identification of their human orthologues. Increasingly, zebrafish experiments are included in studies of human genetic disease, often providing independent verification of the activity of a gene implicated in a human disease 3, 5, 10. In addition to enabling the systematic definition of a large range of early developmental phenotypes, screens in zebrafish have contributed more generally to our understanding of the factors controlling the specification of cell types, organ systems and body axes of vertebrates 7, 8, 9.Īlthough its contributions have already been substantial, zebrafish research holds further promise to enhance our understanding of the detailed roles of specific genes in human diseases, both rare and common. Such investigations have also contributed notably to our understanding of basic vertebrate biology and vertebrate development. These mutations, when driven to homozygosity, can produce defects in a variety of organ systems with pathologies similar to human disease. The systematic application of genetic screens led to the phenotypic characterization of a large collection of mutations 1, 2. The zebrafish ( Danio rerio) was first identified as a genetically tractable organism in the 1980s. In addition, the high quality of this genome assembly provides a clearer understanding of key genomic features such as a unique repeat content, a scarcity of pseudogenes, an enrichment of zebrafish-specific genes on chromosome 4 and chromosomal regions that influence sex determination. Comparison to the human reference genome shows that approximately 70% of human genes have at least one obvious zebrafish orthologue. Detailed automatic and manual annotation provides evidence of more than 26,000 protein-coding genes 6, the largest gene set of any vertebrate so far sequenced. To examine this, we generated a high-quality sequence assembly of the zebrafish genome, made up of an overlapping set of completely sequenced large-insert clones that were ordered and oriented using a high-resolution high-density meiotic map. However, for effective modelling of human genetic disease it is important to understand the extent to which zebrafish genes and gene structures are related to orthologous human genes. The virtually transparent embryos of this species, and the ability to accelerate genetic studies by gene knockdown or overexpression, have led to the widespread use of zebrafish in the detailed investigation of vertebrate gene function and increasingly, the study of human genetic disease 3, 4, 5. Zebrafish have become a popular organism for the study of vertebrate gene function 1, 2. Nature volume 496, pages 498–503 ( 2013) Cite this article The zebrafish reference genome sequence and its relationship to the human genome
0 Comments
Leave a Reply. |