Table 3. Number of candidate genes identified based on different filtering strategies.
Under the dominant model, at least one non-synonymous variant, splice acceptor or donor site variant or coding indel (NS/SS/I) in a gene was required in the gene. Under the recessive model, at least two novel variants were required, and these could be either at the same position (i.e. a homozygous variant) or at two different positions in the same gene (i.e. a potential compound heterozygote, though we were unable to ascertain phase at this stage). In each column is the range for the number of candidate genes for exomes considered individually (column 1) and all combinations of 2 to 4 exomes (columns 2-4). Note that the upper bound on the ranges may be inflated relative to what would be the case if four unrelated, affected individuals had been used because the comparisons in which the two siblings were included provided reduced power compared to unrelated individuals. Columns 5-9 show the number of candidate genes when at least 1, 2, or 3 individuals is required to have one variant in a gene (dominant model) or two or more variants in a gene (recessive model). This is a simple model of genetic heterogeneity or incomplete data. For example, the total number of candidate genes common to any 3 of all 4 exomes is shown in column 9. For columns 5-6, one of the siblings (Kindred 1-B) was not included in the analysis as sibs share 50% of variants.
| Dominant Model | Number of Affected Exomes | Subsets of 3 Exomes | Subsets of all 4 Exomes | |||||
|---|---|---|---|---|---|---|---|---|
| 1 | 2 | 3 | Any 1 | Any 2 | Any 1 | Any 2 | Any 3 | |
| NS/SS/I | 4645-4687 | 3358-3940 | 2850-3099 | 6658 | 4489 | 6943 | 5167 | 3920 |
| … not in dbSNP129 | 634-695 | 136-369 | 72-105 | 1617 | 274 | 1829 | 553 | 172 |
| … not in HapMap 8 | 898-979 | 161-506 | 55-117 | 2336 | 409 | 2628 | 835 | 222 |
| … not in either | 453-528 | 40-228 | 10-26 | 1317 | 109 | 1516 | 333 | 44 |
| … AND predicted damaging | 204-284 | 10-83 | 3-6 | 682 | 37 | 787 | 126 | 11 |
| Recessive Model | Number of Affected Exomes | Subsets of 3 Exomes | Subsets of all 4 Exomes | |||||
| 1 | 2 | 3 | Any 1 | Any 2 | Any 1 | Any 2 | Any 3 | |
| NS/SS/I | 2780-2863 | 1993-2362 | 1646-1810 | 4097 | 2713 | 4293 | 3172 | 2329 |
| … not in dbSNP129 | 92-115 | 30-53 | 22-31 | 226 | 61 | 270 | 90 | 42 |
| … not in HapMap 8 | 111-133 | 13-46 | 5-13 | 329 | 32 | 397 | 75 | 19 |
| … not in either | 31-45 | 2-9 | 2-3 | 100 | 6 | 121 | 14 | 4 |
| … AND predicted damaging | 6-16 | 0-2 | 0-1 | 35 | 2 | 44 | 4 | 1 |