FIGURE

Fig 1

ID
ZDB-FIG-200829-102
Publication
Wilson et al., 2020 - A point mutation decouples the lipid transfer activities of microsomal triglyceride transfer protein
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Fig 1

The <italic>c655</italic> allele is a missense mutation in the M-subunit of microsomal triglyceride transfer protein.

(A) Representative images of a wild-type zebrafish embryo, a homozygous mutant embryo carrying the previously described stalactite (stl) missense mutation in mttp, and a homozygous c655 mutant embryo at 3 days post fertilization (dpf); Scale = 500 μm. The dark/opaque yolk phenotype in embryos from c655 heterozygous in-crosses segregated with a Mendelian ratio consistent with a homozygous recessive mutation, mean +/- SD. For source data, see S4 File. (B) Euclidean distance mapping analysis plots produced by MMAPPR [51], showing the likely genomic region of the c655 mutation. Plot of the LOESS fit to the mapping scores (Euclidean Distance4) across all 25 chromosomes (top) and expanded view of chromosome 1(GRCz10: CM002885.1) (bottom). Single nucleotide variants (SNVs) present in this 11 MB region in c655 mutant embryos were assessed for their effect on annotated genes using the Ensembl Variant Effect Predictor [52], including using the Sorting Intolerant from Tolerant algorithm (SIFT) [53], to predict the impact of changes on protein-coding sequence (tolerated or deleterious). We extracted variants that alter the protein-coding sequence as candidates for the causal mutation (223 variants in 64 genes, of which 42 are missense variants predicted to be deleterious; S1 File). One of the SNVs linked to the c655 phenotype was a G>T missense mutation predicted to be deleterious in exon 18 of the microsomal triglyceride transfer protein gene (ENSDARG00000008637, Chr1:11,421,261 GRCz10, red arrow in B shows the position of the G>T missense mutation in mttp). (C) Representative image of a trans-heterozygous mttpstl/c655 embryo; 3 dpf, scale = 500 μm. The dark/opaque yolk phenotype is present at expected ratios and genotyping confirms that only the embryos with opaque yolks are trans-heterozygous for the mttp alleles. (D) Depiction of the mttp gene structure highlighting the locations of the stl (L475P) (position 11431645 (GRCz10), transcript mtp-204 (ENSDART00000165753.2)) and c655 (G863V) missense alleles in exon 11 and 18, respectively. An additional SNV in mttp at position Chr1:11,421,300 GRCz10 (T>C) causing a missense mutation (M850T) was also identified in c655 mutants; however, this SNV was not predicted to be deleterious and has been previously noted in Ensembl.

Expression Data

Expression Detail
Antibody Labeling
Phenotype Data
Fish:
Observed In:
Stage: Protruding-mouth

Phenotype Detail
Acknowledgments
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