Background
Methods
Sample composition
Evaluation of phenotypes
Identification of conserved sequences
Identification of polymorphisms
CNE | Location in Bac clone AC004039.1 | SNP | Location in Bac clone AC004039.1 | Population | ||
---|---|---|---|---|---|---|
AA | EA | HT | ||||
CNE-A | 48566–48741 | - | - | - | - | - |
SNP1-C/T | 43038 | 3 | 0 | 0 | ||
CNE-B^ | 42346–42674 | - | - | - | - | - |
CNE-C | 32694–33033 | SNP2-C/T | 32711 | 6 | 3 | 3 |
SNP3-C/T | 31971 | 1 | 0 | 0 | ||
SNP4-G/A | 31695 | 1 | 3 | 3 | ||
CNE-D | 31406–31590 | - | - | - | - | - |
SNP5-T/C | 21794 | 1 | 0 | 0 | ||
CNE-E | 21595–21737 | - | - | - | - | - |
SNP6-C/T | 21432 | 4 | 6 | 1 | ||
SNP7-G/A | 21425 | 4 | 6 | 1 | ||
CNE-F* | 17615–17863 | SNP8-G/C | 17713 | 2 | 4 | 1 |
Genotyping
IL13
|
IL4
| Intergenic Region | |||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
Haplotype | Frequency | -1112C/T | +1923C/T | Arg130Gln (G→ A) | -589C/T | SNP2C/T | SNP4G/A | +3017G/T | +8374A/G | SNP7A/G | SNP8C/G |
1 | 0.660 | C | C | G | C | C | G | G | A | A | G |
2 | 0.070 |
T
| C | G | C | C | G | G | A | A | G |
3 | 0.008 | C |
T
|
A
| C | C | G | G | A | A | G |
4 | 0.021 |
T
|
T
|
A
| C | C | G | G | A | A | G |
5 | 0.021 | C | C | G | C | C | G | T | A | G | C |
6 | 0.034 |
T
|
T
|
A
| C | C | G | T | A | G | C |
7 | 0.019 | C |
T
|
A
| C | C | G | T | A | G | C |
8 | 0.068 | C | C | G | T | T | A | T | G | G | C |
9 | 0.098 |
T
|
T
|
A
| T | T | A | T | G | G | C |
Statistical analysis
Linkage disequilibrium
Results
SNP discovery
Patterns of linkage disequilibrium
SNP studies in the hutterites
Specific IgE Response (+SPT) to | |||
---|---|---|---|
Locus 1 | Locus 2 | Mold (N = 75) | Cockroach (N = 148) |
IL13_--1112 | IL13_+1923 |
0.0063
| 0.042 |
SNP2 |
0.00020
|
0.0022
| |
IL4_+3017 | 0.033 |
0.0074
| |
IL13_+1923 | SNP2 |
0.00033
|
0.0017
|
IL4_+3017 | 0.017 | 0.042 |
European Americans
|
African Americans
| |||||||
---|---|---|---|---|---|---|---|---|
SNP | All Asthma | +SPT Any Allergen | +SPT Molds | Controls | All Asthma | +SPT Any Allergen | +SPT Molds | Controls |
(N = 126) | (N = 82) | (N = 46) | (N = 205) | (N = 205) | (N = 160) | (N = 68) | (N = 183) | |
IL13_-1112T | 0.259 | 0.264 | 0.275 | 0.213 | 0.418 | 0.409 | 0.375 | 0.407 |
CC | 0.576 | 0.586 | 0.550 | 0.613 | 0.337 | 0.336 | 0.391 | 0.360 |
CT | 0.330 | 0.300 | 0.350 | 0.348 | 0.489 | 0.510 | 0.469 | 0.467 |
TT | 0.094 | 0.114 | 0.100 | 0.039 | 0.174 | 0.154 | 0.140 | 0.173 |
IL13_+1923T | 0.245 | 0.282 | 0.238 | 0.227 | 0.666 | 0.664 | 0.672 | 0.660 |
CC | 0.575 | 0.535 | 0.575 | 0.584 | 0.087 | 0.094 | 0.094 | 0.133 |
CT | 0.359 | 0.366 | 0.375 | 0.376 | 0.495 | 0.483 | 0.469 | 0.413 |
TT | 0.066 | 0.099 | 0.050 | 0.040 | 0.418 | 0.423 | 0.437 | 0.454 |
IL13_Gln (T) | 0.221 | 0.254 | 0.272 | 0.202 | 0.192 | 0.191 | 0.161 | 0.169 |
Arg/Arg (C/C) | 0.618 | 0.577 | 0.625 | 0.620 | 0.643 | 0.639 | 0.695 | 0.686 |
Arg/Gln (C/T) | 0.324 | 0.338 | 0.325 | 0.355 | 0.330 | 0.340 | 0.288 | 0.290 |
Gln/Gln (T/T) | 0.058 | 0.085 | 0.05 | 0.025 | 0.027 | 0.021 | 0.077 | 0.024 |
IL4_-589T | 0.193 | 0.197 | 0.163 | 0.163 | 0.677 | 0.678 | 0.687 | 0.643 |
CC | 0.670 | 0.662 | 0.700 | 0.702 | 0.115 | 0.128 | 0.125 | 0.133 |
CT | 0.274 | 0.282 | 0.275 | 0.270 | 0.397 | 0.389 | 0.375 | 0.447 |
TT | 0.056 | 0.056 | 0.025 | 0.028 | 0.478 | 0.483 | 0.5 | 0.420 |
CNE-C_SNP2-T | 0.196 | 0.223 | 0.257 | 0.146 | 0.405 | 0.419 | 0.404 | 0.382 |
CC | 0.667 | 0.600 | 0.541 | 0.730 | 0.333 | 0.316 | 0.333 | 0.382 |
CT | 0.294 | 0.354 | 0.405 | 0.247 | 0.524 | 0.530 | 0.526 | 0.471 |
TT | 0.049 | 0.046 | 0.054 | 0.023 | 0.143 | 0.154 | 0.141 | 0.147 |
SNP4-A | 0.176 | 0.186 | 0.187 | 0.175 | 0.399 | 0.412 | 0.415 | 0.359 |
GG | 0.692 | 0.661 | 0.656 | 0.675 | 0.340 | 0.323 | 0.321 | 0.415 |
GA | 0.264 | 0.305 | 0.313 | 0.300 | 0.525 | 0.531 | 0.528 | 0.452 |
AA | 0.044 | 0.034 | 0.031 | 0.025 | 0.135 | 0.146 | 0.151 | 0.132 |
IL4_+3017T | 0.327 | 0.339 | 0.387 | 0.308 | 0.850 | 0.867 | 0.825 | 0.805 |
GG | 0.490 | 0.452 | 0.382 | 0.478 | 0.045 | 0.061 | 0.067 | 0.051 |
TG | 0.367 | 0.419 | 0.471 | 0.429 | 0.209 | 0.217 | 0.217 | 0.288 |
TT | 0.143 | 0. 129 | 0.147 | 0.093 | 0.746 | 0. 727 | 0.716 | 0.661 |
IL4_+8374G | 0.161 | 0.164 | 0.135 | 0.159 | 0.275 | 0.274 | 0.259 | 0.257 |
AA | 0.708 | 0.687 | 0.730 | 0.703 | 0.526 | 0.533 | 0.554 | 0.541 |
AG | 0.261 | 0.299 | 0.270 | 0.275 | 0.398 | 0.387 | 0.375 | 0.404 |
GG | 0.031 | 0.014 | 0 | 0.022 | 0.076 | 0.080 | 0.071 | 0.055 |
SNP7-G | 0.279 | 0.318 | 0.319 | 0.317 | 0.636 | 0.638 | 0.614 | 0.568 |
AA | 0.548 | 0.485 | 0.472 | 0.458 | 0.156 | 0.152 | 0.123 | 0.213 |
AG | 0.347 | 0.394 | 0.417 | 0.450 | 0.416 | 0.421 | 0.526 | 0.460 |
GG | 0.105 | 0.121 | 0.111 | 0.092 | 0.428 | 0.427 | 0.351 | 0.327 |
CNE-F_SNP8-C | 0.323 | 0.339 | 0.386 | 0.293 | 0.618 | 0.623 | 0.598 | 0.577 |
CC | 0.131 | 0.113 | 0.143 | 0.081 | 0.393 | 0.401 | 0.328 | 0.335 |
CG | 0.384 | 0.452 | 0.486 | 0.422 | 0.450 | 0.444 | 0.541 | 0.484 |
GG | 0.485 | 0.435 | 0.371 | 0.497 | 0.157 | 0.156 | 0.131 | 0.181 |
Studies in outbred case-control samples
Locus 1 | Locus 2 | Asthma vs. Controls | +SPT to Any Allergen vs. Controls | +SPT Molds vs. Controls |
---|---|---|---|---|
a) European Americans
| ||||
IL13_-1112 | IL4_+3017 | ns | ns | 0.0128 |
IL13_+1923 | IL13_130 |
<10
-4
| 0.0011 | 0.0121 |
IL13_130 | SNP2 | ns | 0.0295 | 0.0101 |
IL4_-589 | SNP2 |
<10
-4
|
0.0004
| 0.0026 |
SNP4 |
<10
-4
|
<10
-4
|
0.0005
| |
IL4_+3017 |
0.0003
| 0.0030 | 0.0269 | |
IL4_+8374 |
<10
-4
|
<10
-4
|
0.0002
| |
SNP7 | 0.0021 | 0.0279 | 0.0335 | |
SNP8 |
0.0002
| 0.0072 | 0.0155 | |
SNP2 | SNP4 | ns | 0.0240 | 0.0042 |
IL4_+3017 | ns | 0.0131 |
<10
-4
| |
IL4_+8374 | ns | 0.0252 | 0.0054 | |
SNP7 | ns | ns | 0.0019 | |
SNP8 | ns | ns | 0.0128 | |
IL4_+3017 | SNP7 | ns | ns | 0.014 |
SNP7 | SNP8 | ns | ns | 0.014 |
b) African Americans
| ||||
IL13_-1112 | IL13_+1923 | ns | ns | 0.009 |
IL4_+3017 | 0.034 | ns | 0.005 |