Fig. 5. Rare copy-number variants (CNVs) in spina bifida (SB) cases participate in SB-relevant pathways and affect various aspects of one-carbon metabolism.

(a) Signaling pathways enriched in cases by gene disrupting, rare coding CNVs detected in the US and Qatar cohorts. Shown are Ingenuity Pathway Analysis (IPA) plots. Several of these pathways in both cohorts emerged as enriched in SB cases. PCP planar cell polarity, RAR retinoic acid receptor. (b) Metabolic processes of choline transport and one-carbon metabolism that are disrupted by rare coding CNVs found in SB cases are labeled 1–6. Purple = deletions; blue = duplications. Their corresponding CNVs are represented in the lower panel in (b) using the Integrative Genomics Viewer (IGV) (for CNV 1–5) and samplot (for CNV 6). Chol choline, Hcy homocysteine, Gly glycine.