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Comment
. 2020 Mar 10;117(10):5097-5099.
doi: 10.1073/pnas.2000944117. Epub 2020 Feb 18.

Dietary modification, penetrance, and the origins of congenital malformation

Greg Gibson  1 , Kiera Berger  2
Affiliations
Comment

Dietary modification, penetrance, and the origins of congenital malformation

Greg Gibson et al. Proc Natl Acad Sci U S A. .
No abstract available

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Conflict of interest statement

The authors declare no competing interest.

Figures

Fig. 1.
Fig. 1.
Evidence of the potential for genotype-by-environment interaction (G×E) in congenital NAD deficiency. (A) There are three pathways involved in synthesis of NAD pools. The de novo kynenurine pathway from tryptophan involves over a dozen enzymes, two of which catalyze enzymatic steps involving 3-hydroxyanthranilic acid, while a third is the final step. Biallelic mutations in all three of genes have been shown to cause VCRL syndrome. (B) Cuny et al. (2) tested various combinations of dietary supplementation of tryptophan in water at standard levels, reduced (600 mg/L) or low (500 mg/L) with heterozygosity for a null allele of the Haao gene. Bar graphs show the proportion of dead embryos (gray) or malformed embryos (dark orange, at least two defects; light orange, one defect) in each combination. Low tryptophan levels can cause phenocopies in wild-type mice, whereas reduced gene and nutrient dosage leads to G×E.
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Comment on

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