Orthology discussion page (Retired)

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This is the place for general discussions of methods, problems or ideas regarding general principles for establishing orthology between reference genome genes and the human disease gene targets.

Specific discussion of gene specific issues should be directed toward the gene specific pages. A link will be added here as soon as the pages are established.

ZFIN Orthology Determination Method

We always use the same methods as outlined here:

1. Check to see if orthology has already been established between a zebrafish gene and the human gene by searching in ZFIN.

2. If there is no established zebrafish ortholog, the human sequence is used to search zebrafish mRNA, Vega and Ensembl transcripts and protein sequences for potential orthologs. If there are several zebrafish sequences that are candidates for being the ortholog, reciprocal blasts of the zebrafish sequences against human sequences are used to order them. The best matches are then analyzed for conserved synteny with the human gene.

The current version of the zebrafish assembly at Ensembl is used to determine the location of the zebrafish gene. After the zebrafish gene has been localized, the flanking regions around the gene are analyzed for other orthologous genes between zebrafish and human chromosomes. The presence of conserved synteny is used as evidence to confirm orthology and the human gene is assigned as the ortholog of the zebrafish gene in ZFIN. If necessary, the zebrafish gene nomenclature in ZFIN is updated.

In cases, where sequence analyses and synteny do not provide clear evidence to distinguish between two or more zebrafish genes, orthology is not established. This is also the case for human genes that do not match any zebrafish cDNA or EST sequences but have a sequence match in the zebrafish genome. Genscan or FGENESH identifiers are instead provided as identfiers for putative zebrafish orthologs.