Additional file 1 of Investigating the dark-side of the genome: a barrier to human disease variant discovery?
Creators: name: Ryan, Niamh M.
name: Corvin, Aiden
Publisher: name: figshare
Year: 2024
Subjects: subject: Genetics
subject: FOS: Biological sciences

description: Additional file 1: Methods S1. Table S1. GO enrichment analysis for the Schizophrenia dark genes vs genome generated 17 FDR significant GO terms. Table S2. GO enrichment analysis for the BMI dark genes vs rest of the genome generated 228 FDR significant GO terms, of which the top 30 are presented in this table. Table S3. GO enrichment analysis for the MDD GWAS genes with dark regions vs rest of the genome returned 45 FDR significant GO terms, of which the top 30 are represented in this table. Table S4. Results of the GO enrichment for the Cholesterol GWAS dark vs rest of genome, showing the top 30 enriched GO terms (out of 433 terms with p-value&lt; 0.05, but not FDR significant). Table S5. Results of the GO enrichment for the Crohn’s dark vs genome, showing the top 30 enriched GO terms (out of 438 terms with p-value&lt; 0.05, but not FDR significant). Table S6. Results of the GO enrichment for the ASD dark vs genome, showing the top 30 enriched GO terms (out of 106 terms with p-value&lt; 0.05, but not FDR significant). Table S7. Results of the GO enrichment for the ALS GWAS dark genes vs rest of the genome, showing the top 30 enriched GO terms (out of 185 terms with p-value&lt; 0.05 but not FDR significant). Table S8. Results of the GO enrichment for the BD GWAS dark genes vs rest of the genome, showing the top 30 enriched GO terms (out of 160 terms with p-value&lt; 0.05 but not FDR significant). Table S9. SCZ darkCDS vs genome. Table S10. Results of the GO enrichment for the Schizophrenia dark CDS vs remaining GRL genes. No terms were FDR significant, however, five terms with p&lt; 0.05 were returned, all related to brain development. Table S11. BMIdarkCDS vs genome Table S12. Top 20 GO terms for the BMI dark CDS vs remaining GRL genes. No FDR significant terms, however, 35 terms with p&lt; 0.05 were returned. Table S13. MDDdarkCDS vs genome. Table S14. Top 20 GO terms for the MDD GWAS genes with dark CDS vs remaining GWAS genes. In total 40 terms (p&lt; 0.05 but not FDR significant) were returned. Table S15. All 22 SCHEMA genes with p&lt;0.05 with at least partially dark CDS regions of which ten genes have &gt;5% dark CDS. Table S16. Subset of ASD associated genes from the ASC which have dark CDS regions, of which two genes have &gt;5% dark CDS. Table S17. SFARI Score 1 (High Confidence) genes with dark CDS regions, of which four genes have &gt;5% dark CDS. Figure S1. Modified browser views of RAC3 from A. GnomAD Browser of human genetic variation (showing the average read depth of both whole exome and whole genome sequencing data) and B. SCHEMA Browser of SCZ associated rare variants. Note for each browser the conspicuous absence of any genetic variants (pathogenic or benign) from low read-depth (dark) regions from exome and whole genome sequencing data, in particular for exon 1. Figure S2. Modified browser views of TRAPPC10 from A. GnomAD Browser of human genetic variation (showing the average read depth of both whole exome and whole genome sequencing data) and B. SCHEMA Browser of SCZ associated rare variants. Figure S3. Modified browser views of UBE2L3 from A. GnomAD Browser of human genetic variation (showing the average read depth of both whole exome and whole genome sequencing data) and B. SCHEMA Browser of SCZ associated rare variants. Note for each browser the conspicuous absence of any genetic variants (pathogenic or benign) from low read-depth (dark) regions from exome and whole genome sequencing data, in particular for exon 1. Figure S4. Modified browser views of FAM86B1 from A. GnomAD Browser of human genetic variation (showing the average read depth of both whole exome and whole genome sequencing data) and B. SCHEMA Browser of SCZ associated rare variants. Note for each browser the conspicuous absence of any genetic variants (pathogenic or benign) from low read-depth (dark) regions from exome and whole genome sequencing data, across five of seven exons. Figure S5. Modified browser views of CORO1A from A. GnomAD Browser of human genetic variation (showing the average read depth of both whole exome and whole genome sequencing data); B. SCHEMA Browser of SCZ associated rare variants and C. Autism Sequencing Consortium Browser of rare variants. Note for each browser the conspicuous absence of any genetic variants (pathogenic or benign) from low read-depth (dark) regions from exome and whole genome sequencing data, in particular exon 10. Figure S5. Modified browser views of SHANK2 from A. GnomAD Browser of human genetic variation (showing the average read depth of both whole exome and whole genome sequencing data); B. SCHEMA Browser of SCZ associated rare variants and C. Autism Sequencing Consortium Browser of rare variants. Note for each browser the conspicuous absence of any genetic variants (pathogenic or benign) from low read-depth (dark) regions from exome and whole genome sequencing data. Figure S6. Modified browser views of ARX from A. GnomAD Browser of human genetic variation (showing the average read depth of both whole exome and whole genome sequencing data); B. SCHEMA Browser of SCZ associated rare variants and C. Autism Sequencing Consortium Browser of rare variants. Note for each browser the conspicuous absence of any genetic variants (pathogenic or benign) from low read-depth (dark) regions from exome and whole genome sequencing data, in particular exon 2. Figure S7. Modified browser views of CASZ1 from A. GnomAD Browser of human genetic variation (showing the average read depth of both whole exome and whole genome sequencing data); B. SCHEMA Browser of SCZ associated rare variants and C. Autism Sequencing Consortium Browser of rare variants. Note for each browser the conspicuous absence of any genetic variants (pathogenic or benign) from low read-depth (dark) regions from exome and whole genome sequencing data, in particular exons 9, 18 (alternatively spliced) and 19. Figure S8. Percentage of genes from SFARI (Score 1, Score 2, Score 3, Syndromic or absent from SFARI) with dark regions, stratified by ASC association q-values (less than 0.1; 0.1 to 0.3, greater than 0.3). This table shows that the SFARI genes with the greatest enrichment of dark gene bodies are those categorised as either Score 2 (High Confidence) or Syndromic, with ASC association q-values &gt; 0.3.