Computational protocol: WNK1/HSN2 Mutation in Human Peripheral Neuropathy Deregulates KCC2 Expression and Posterior Lateral Line Development in Zebrafish (Danio rerio)

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Protocol publication

[…] The sequence of human WNK1 was used to find homolog sequences in GenBank, leading to the identification of the Xenopus laevis ortholog of WNK1. We then used this ortholog sequence to search the zebrafish assembly using the BLAT genome browser from UCSC ( The identified genomic sequence from zebrafish was then analyzed, and exons were identified through EST alignments or comparative genomic techniques. cDNA sequences were reconstituted based on the predicted exons and ORFs from the predicted cDNAs were used to derived the predicted peptide sequences. Exons were numbered from 1–28 and the HSN2 name was conserved for the target exon present only in the zebrafish wnk1b (chromosome 4). Orthologous protein sequences were aligned using CLUSTALW and amino acid identity/similarity was calculated using MatGAT program v2.01.Exons 11 to 13 are fused, as is the case with Fugu and Tetradon, and exon 10 has been split in two smaller exons. The human WNK1 and zebrafish wnk1b orthologs are 47.4% identical and 56.8% similar along the full length of the proteins. We also compared the HSN2 exon sequence, but since the human putative exon 8b sequence contains several frameshifting mutations, the chimp sequence was used instead for comparison purposes. Chimp and zebrafish wnk1b HSN2-like peptide sequences are well conserved, being 54.7% similar and 38.2% identical. […]

Pipeline specifications

Software tools BLAT, Clustal W, MatGAT
Application Genome data visualization
Organisms Danio rerio, Homo sapiens
Diseases Autonomic Nervous System Diseases, Peripheral Nervous System Diseases
Chemicals Potassium Chloride