Table 1.
Distribution of single nucleotide variants (SNVs) between probands and siblings.
| Category | Total number of SNVs a | SNVs per subject | Per base SNV rate (×10-8) | p b | Odds ratio (95% CI) c | |||||
|---|---|---|---|---|---|---|---|---|---|---|
| Pro | Sib | Pro | Sib | Pro | Sib | |||||
| N=200 | N=200 | N=200 | N=200 | N=200 | N=200 | |||||
| De novo | All genes | All | 154 | 125 d | 0.77 | 0.63 | 1.58 | 1.31 | 0.09 | NA |
| Silent | 29 | 39 | 0.15 | 0.20 | 0.29 | 0.40 | 0.28 | NA | ||
| All non-synonymous | 125 | 87 | 0.63 | 0.44 | 1.29 | 0.92 | 0.01* | 1.93 (1.11-3.36) | ||
| Missense | 110 | 82 | 0.55 | 0.41 | 1.13 | 0.86 | 0.05 | 1.80 (1.03-3.16) | ||
| Nonsense/splice site | 15 | 5 | 0.08 | 0.03 | 0.16 | 0.05 | 0.04* | 4.03 (1.32-12.4) | ||
| Brain-expressed genes | All | 137 | 96 | 0.69 | 0.48 | 1.41 | 1.01 | 0.01* | NA | |
| Silent | 23 | 30 | 0.12 | 0.15 | 0.24 | 0.31 | 0.41 | NA | ||
| All non-synonymous | 114 | 67 | 0.57 | 0.34 | 1.18 | 0.71 | 0.001* | 2.22 (1.19-4.13) | ||
| Missense | 101 | 64 | 0.51 | 0.32 | 1.04 | 0.68 | 0.005* | 2.06 (1.10-3.85) | ||
| Nonsense/ splice site | 13 | 3 | 0.07 | 0.02 | 0.14 | 0.03 | 0.02* | 5.65 (1.44-22.2) | ||
| Novel transmitted | All genes | All | 26,565 | 26,542 | 133 | 133 | 277 | 277 | 0.92 | NA |
| Silent | 8,567 | 8,642 | 43 | 43 | 90 | 91 | 0.57 | NA | ||
| All non-synonymous | 17,998 | 17,900 | 90 | 90 | 188 | 187 | 0.61 | 1.01 (0.98-1.05) | ||
| Missense | 17,348 | 17,250 | 87 | 86 | 181 | 180 | 0.60 | 1.01 (0.98-1.05) | ||
| Nonsense/splice site | 650 | 650 | 3.3 | 3.3 | 7 | 7 | 1.00 | 1.01 (0.90-1.13) | ||
| Brain-expressed genes | All | 20,942 | 20,982 | 105 | 105 | 219 | 220 | 0.85 | NA | |
| Silent | 6,884 | 6,981 | 34 | 35 | 72 | 74 | 0.42 | NA | ||
| All non-synonymous | 14,058 | 14,001 | 70 | 70 | 147 | 146 | 0.74 | 1.02 (0.98-1.06) | ||
| Missense | 13,588 | 13,525 | 68 | 68 | 142 | 141 | 0.71 | 1.02 (0.98-1.06) | ||
| Nonsense/splice site | 470 | 476 | 2.3 | 2.4 | 5 | 5 | 0.87 | 1.00 (0.88-1.14) | ||
An additional 15 de novo variants were seen in the probands of 25 trio families; all were missense and 14 were brain-expressed.
The p-values compare the number of variants between probands and siblings using a two-tailed binomial exact test (Supplementary Information).
The odds ratio calculates the proportion of variants in a specific category to silent variants and then compares these ratios in probands versus siblings.
The sum of silent and non-synonymous variants is 126, however one nonsense and two silent de novo variants were indentified in KANK1 in a single sibling, suggesting a single gene conversion event. This event contributed a maximum count of one to any analysis.