Figure 2

Figure 2

Zebrafish orthologs of human neurological disease genes vary with respect to duplicate retention and average protein size. (A) Gene duplicate retention rates in zebrafish are graphed for neurodevelopmental and neurodegenerative disease groups. Yellow numbers at the base of bars represent sample size. (B) Protein sizes of zebrafish orthologs of human disease genes with floating box plots (median with upper and lower quartile-box and range-whiskers). Note some larger proteins are outliers that fall outside of the calculated range. These gene sets for each human disease only incorporate a small percentage of associated genes and selection criteria varied because of the heterogeneity in genes linked to each disease and an emphasis on producing conservative lists. Each gene set was selected using data from research groups and review articles with the goal of including only the highest confidence disease genes based on either statistical thresholds and/or reoccurrence. Autism spectrum disorders (ASD) genes were chosen from the Simons Foundation Autism Initiative (SFARI.org) “high confidence” and “strong candidate” gene lists, which uses a multi-variable scoring analysis that includes sample size, statistical significance, replication, and functional analysis (Basu et al., 2009). ASD-intellectual disability (ID) genes were found in four separate reviews that provide evidence for reoccurrence in both ASD and ID (Kaufman et al., 2010; Krumm et al., 2014; Srivastava et al., 2014; Vissers et al., 2016). Schizophrenia (SCZ) genes were chosen from a SCZ genetics review, however this list is small and does not provide a confidence level for the disease contribution of each gene (Escudero and Johnstone, 2014). X-linked ID genes (Piton et al., 2013) and Charcot-Marie Tooth Disease (CMT; Timmerman et al., 2014) genes were chosen from recent meta-analyses to which we included a threshold of >5 cases per gene. Autosomal dominant and recessive and X-linked ataxia (ATX; Bird, 2016) and Hereditary Spastic Paraplegia (HSP; Fink, 2014) genes were chosen with well-known inheritance pedigrees. Human proteins for these gene lists were generated using BioMart (Kinsella et al., 2011) and the longest isoforms were used to identify zebrafish orthologs (Supplementary Material, Tables S1–7). Human proteins were then Blasted (Flicek et al., 2014) against the zebrafish proteome and ortholog information was recorded. Zebrafish proteins with low percent coverage, protein identity, e-value and ambiguous gene annotation (e.g., gene-like, LOC1084, etc.) were reciprocally blasted to confirm orthology.