Table 4.
Results of Gene-Dropping Simulations
| Disease | Gene Mutation | Carrier Frequency in Hutterites | Number of Founders Ancestral to All Carriers | Most Likely Model | Probability of Reaching Frequency under Neutral Model (95% CI) | Probability of Reaching Frequency under 0 Fitness Model (95% CI) |
|---|---|---|---|---|---|---|
| Limb girdle muscular dystrophy 2H | TRIM32 p.Asp487Asn | 0.153 | 12 | 1 | 0.0318 (3.1 × 10−4) | 0.0188 (2.4 × 10−4) |
| Oculocutaneous albinism type 1A | TYR p.Cys91Tyr | 0.141 | 15 | 1 | 0.0382 (3.1 × 10−4) | 0.0256 (2.5 × 10−4) |
| Spinal muscular atrophy Type III | SMN1 exon 7 del | 0.127 | 13 | 0 | 0.0574 (4.0 × 10−4) | 0.0427 (3.5 × 10−4) |
| Limb girdle muscular dystrophy 2I | FKRP p.Leu276Ile | 0.107 | 17 | 1 | 0.0711 (3.9 × 10−4) | 0.0575 (3.5 × 10−4) |
| Sitosterolemia | ABCG8 p.Ser107Ter | 0.084 | 16 | 1 | 0.1256 (5.1 × 10−4) | 0.1110 (4.9 × 10−4) |
| Joubert syndrome | TMEM237 p.Arg18Ter | 0.080 | 17 | 0 | 0.1405 (5.2 × 10−4) | 0.1261 (5.0 × 10−4) |
| Cystic fibrosis | CFTR p.Met1101Lys | 0.073 | 18 | 0 | 0.1198 (4.7 × 10−4) | 0.1089 (4.6 × 10−4) |
| Nonsyndromic mental retardation | TECR p.Pro182Leu | 0.069 | 18 | 0 | 0.1631 (5.4 × 10−4) | 0.1513 (5.2 × 10−4) |
| Restrictive dermopathy | ZMPSTE24 c.1085dupT | 0.064 | 26 | 0 | 0.1518 (4.4 × 10−4) | 0.1432 (4.3 × 10−4) |
| Nonsyndromic deafness | GJB2 c.35delG | 0.036 | 27 | 1 | 0.2607 (5.2 × 10−4) | 0.2546 (5.2 × 10−4) |
| Dilated cardiomyopathy with ataxia syndrome | DNAJC19 IVS3-1G>C | 0.029 | 28 | 0 | 0.2909 (5.3 × 10−4) | 0.2862 (5.3 × 10−4) |
| Bardet-Biedl syndrome | BBS2 IVS3-2A>G | 0.028 | 22 | 0 | 0.3214 (6.2 × 10−4) | 0.3164 (6.2 × 10−4) |
| Usher syndrome type 1F | PCDH15 c.1471delT | 0.025 | 20 | 0 | 0.3221 (6.5 × 10−4) | 0.3175 (6.5 × 10−4) |
| Cystic fibrosis | CFTR p.Phe508del | 0.022 | 30 | 0 | 0.3437 (5.4 × 10−4) | 0.3399 (5.4 × 10−4) |
This table is ordered by carrier frequency. The probability that each of the 14 AR mutations reached the carrier frequency observed in our study sample is shown in the last two columns. Probabilities are given for two extreme models: a neutral model and a zero fitness (lethal) model. The more appropriate model based on clinical phenotypes is indicated in column 4 (1 = neutral model; 0 = lethal model). We use common mutation names to retain consistency with the existing literature. The following abbreviation is used: CI, confidence interval.