Table 3. Extreme ASE and biallelic LOE events with significantly altered gene expression.
| Gene | ID | Tissue | Proband Expr* | Mean Expr ±s.d. (n) | Fold | P value† | PCGC cases LOF AF | PCGC controls LOF AF | ExAC LOF AF | |
|---|---|---|---|---|---|---|---|---|---|---|
| ASE genes with loss of allele expression | ||||||||||
| RBFOX2‡,§ | 1-05368 | DuctArt | 189.1 | 296±44 (15) | 0.64 | 1.6 × 10−2 | 1.4 × 10−3 | 0 | 1.8 × 10−5 | |
| SGSM1‡,§ | 1-01019 | RA | 60.3 | 133±51 (18) | 0.45 | 4.7 × 10−2 | 9.4 × 10−4 | 0 | 9.1 × 10−5 | |
| AARSD1 | 1-00384 | IVS | 65.9 | 108±12 (7) | 0.61 | 3.0 × 10−4 | 0 | 0 | 0 | |
| C5orf46 | 1-00713 | LV | 7.7 | 42±17 (9) | 0.18 | 4.4 × 10−2 | 0 | 0 | 9.1 × 10−5 | |
| SDHB | C417-01C417-01 | IVSLV | 169.6124.0 | 302±25 (7)224±46 (9) | 0.560.55 | <1.0 × 10−43.0 × 10−2 | 0 | 0 | 8.2 × 10−5 | |
| CBR1 | CHD-1548CHD-1548CHD-1548 | LALVRA | 12.915.110.6 | 29±6.0 (10)25±3.0 (7)26±3.4 (9) | 0.440.600.41 | 6.1 × 10−38.0 × 10−4<1.0 × 10−4 | 0 | 2.8 × 10−4 | 2.6 × 10−3 | |
| ASE genes with gain of allele expression | ||||||||||
| FGFBP2 | 1-01024 | RA | 5.6 | 1.0±1.7 (15) | 5.48 | 6.7 × 10−3 | 9.5 × 10−4 | 5.6 × 10−4 | 4.5 × 10−4 | |
| FGFBP2 | 1-01984 | LA | 9.2 | 1.4±0.4 (3) | 6.86 | <1.0 × 10−4 | 9.5 × 10−4 | 5.6 × 10−4 | 4.5 × 10−4 | |
| MYOZ1 | 1-02697 | RV | 26.9 | 4.2±3.5 (16) | 6.45 | <1.0 × 10−4 | 0 | 2.7 × 10−4 | 3.5 × 10−4 | |
| Genes with loss of expression of both alleles | ||||||||||
| LBH§ | 1-03051 | AO | 5.4 | 55±15 (6) | 0.10 | 8.0 × 10−4 | 0|| | 0|| | 0|| | |
| ZBTB16§ | 1-03316 | AO | 1.2 | 22±5.8 (6) | 0.06 | 3.0 × 10−4 | 0|| | 0|| | 0|| | |
| IRX5 | 1-03948¶ | RV | 0.6 | 13±4.1 (20) | 0.05 | 1.9 × 10−3 | 0|| | 0|| | 0|| | |
| PHKG1 | 1-00596¶ | RA | 2.6 | 30±8.7 (47) | 0.09 | 1.5 × 10−3 | 0|| | 0|| | 1.6 × 10−5|| | |
| FRG1B | 1-04119 | PA | 0.3 | 5.4±1.1 (10) | 0.06 | <1.0 × 10−4 | 0|| | 0|| | 0|| | |
| TRMT2B | 1-02921 | RV | 0.0 | 5.5±1.3 (20) | 0 | <1.0 × 10−4 | 0|| | 0|| | 2.6 × 10−4|| | |
| PHKG1# | 1-03948¶ | RV | 0.6 | 15±8.1 (20) | 0.04 | 4.0 × 10−2 | 0|| | 0|| | 1.6 × 10−5|| | |
| FGFBP2#,§ | 1-02697 | PV | 0.5 | 14±3.4 (3) | 0.04 | 1.0 × 10−4 | 0|| | 0|| | 1.6 × 10−5|| | |
AF, allele frequency; AO, aorta; ASE, allele-specific expression; CHD, congenital heart disease; DuctArt, ductus arteriosus; ExAC, Exome Aggregation Consortium; IVS, interventricular septum; LA, left atrium; LOE, loss-of-expression; LOF, loss-of-function; LV, left ventricle; PA, pulmonary artery; PCGC, Pediatric Cardiac Genomics Consortium; PV, pulmonary valve; RA, right atrium; RV, right ventricle.
*Expression in reads per million aligned reads.
†P value calculated from z-score.
‡Includes de novo LOF mutations.
§Strong candidate CHD genes (identified in this study).
||Frequency of homozygous (ExAC) or combined homozygous and compound heterozygous (PCGC cases and controls) LOF mutations.
¶KMT2D de novo mutations identified in both 1-03948 (LOF) and 1-00596 (damaging-missense).
#LOE genes PHKG1 (1-03948, P>2.7 × 10−3) and FGFBP2 (1-02697, n=3) are not significant on their own, but occur in genes significant in other subjects.