Table 3.
Evaluation of the rates of de novo mutations in cases with intellectual disability. (a) The observed and expected rate of mutations by type per exome for cases of intellectual disability (ID)9,10. (b) The number of genes with multiple de novo mutations in intellectual disability cases across studies. The average number of expected genes with multiple de novo mutations was determined by simulation. LoF = Loss-of-function. DNMs = de novo mutations.
| a) Genome-wide excesses of mutational events | ||||
|---|---|---|---|---|
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| ID Cases | ||||
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| Mutation Type | Observed events per exome | Expected events per exome | p-value | |
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| Synonymous | 0.19 | 0.27 | 0.0267 | Two-tailed |
| Missense | 0.70 | 0.62 | 0.2380 | Two-tailed |
| Loss-of-Function | 0.24 | 0.09 | 6.49E-07 | One-tailed |
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| n = 151 families | ||||
| b) Genome-wide excesses of multiply hit genes | |||
|---|---|---|---|
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| ID Cases | |||
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| Mutation Type | Observed genes with 2+ DNMs | Average expected genes with 2+ DNMs | p-value |
| Synonymous | 1 | 0.09 | 0.0879 |
| Missense | 3 | 0.5 | 0.0090 |
| LoF | 2 | 0.01 | < 0.001 |
| LoF+missense | 6 | 0.6 | < 0.001 |
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| n = 151 families | |||