Introduction
Methodology in genetic studies of complex traits
Microsatellite marker analysis
Study designs in analyses of complex genetic traits
Linkage and candidate gene studies in asthma and atopy
Linkage studies
Study | |||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Hizawa | Daniels | Ober | Ober | Wjst | Yokouchi | Lee | Cookson | ||||||
CSGA 1 | et al. | et al. | et al. | et al. | et al. | et al. | EGEA | et al. | et al. | ||||
(1997) | (1998) | (1996) | (1998) | (2000)† | (1999) | (2000) | (2000) | (2000) | (2001) | ||||
C | C | C | C (German/ | C | C | C | C | ||||||
Population | AA | C | H | AA | C | (Australian) | (Hutterites) | (Hutterites) | Swedish) | Japanese | (French) | (German) | (British) |
Individuals (n) | 117‡ | 215‡ | 48‡ | 281 | 299 | 364 | 371/292 | 693 | 415 | 196 | 493 | 839 | |
Sib-pairs (n) | ns | ns | ns | ns | ns | 172 | ns | ns | 156 | 65 | ns | 199 | 213 |
1q21 | AD* | ||||||||||||
1p31 | Asthma * | ||||||||||||
2pter | Asthma*, IgE** | ||||||||||||
BHR*, RAST** | |||||||||||||
2q22-33 | Asthma* | IgE* | |||||||||||
3q21 | AD*** | ||||||||||||
4q35 | BHR**, atopy* | Asthma** | |||||||||||
5p13-15 | Asthma** | BHR | |||||||||||
(D5S1470) | |||||||||||||
5q23-33 | IgE* | BHR** | BHR | Asthma*** | |||||||||
(D5S1462) | |||||||||||||
6p21.3-23 | IgE* | Eos*** | Asthma*, IgE* | ||||||||||
RAST* | |||||||||||||
7p | IgE*, BHR** | ||||||||||||
(D7S2250, D7S484) | |||||||||||||
8p23.3 | IgE* | Asthma | |||||||||||
(D8S1136) | |||||||||||||
9 (DS1784) | Asthma*, IgE* | ||||||||||||
RAST* | |||||||||||||
11p13-15 | Asthma* | IgE* | |||||||||||
11q13 | IgE**, ST*** | IgE* | |||||||||||
12q13-24.2 | Asthma* | BHR* | Asthma* | Eos** | |||||||||
13q11-32.2 | Asthma* | IgE* | Atopy** | Asthma** | Eos* | ||||||||
14q11.2-13 | Asthma* | ||||||||||||
14q32 | BHR | ||||||||||||
(gata193a07) | |||||||||||||
16q-tel | IgE** | ||||||||||||
16q23-24 | IgE** | ST (D16S539) | |||||||||||
17p11.1-q11.2 | Asthma* | ||||||||||||
17q12-21 | Asthma/ST* | ||||||||||||
17q25 | AD** | ||||||||||||
19q13 | Asthma* | Asthma* | BHR | BHR* | |||||||||
(D19S900) | |||||||||||||
20p | Asthma** | ||||||||||||
21q21 | Asthma* |
Chromosomal region | Phenotype (linkage) | Population | Reference |
---|---|---|---|
5q23-33 | Total IgE | Dutch, Amish, Caucasian (UK) | |
Total IgE, specific IgE, eosinophil count | Australian | [S11] | |
Specific IgE | African American | [S12]* | |
Atopic dermatitis | Caucasian (UK), German/Swedish | ||
Asthma/atopy | Japanese | ||
Eosinophil count | Caucasian (US) | [S16] | |
Hypereosinophilia | Caucasian (US) | [S17] | |
Bronchial hyperresponsiveness | Dutch, Hutterites | ||
6p21-23 | Specific IgE | Caucasian (US) | |
Asthma, IgE | German/Swedish | [S5]* | |
Allergic asthma | Colombian | [S20] | |
Eosinophil count | Caucasian (Australian) | [S2]* | |
11q13 | IgE | Caucasian (UK) | |
IgE, positive skin test | Caucasian (Australian) | [S2]* | |
Specific IgE | Caucasian (Australian), African American | ||
Bronchial hyperresponsiveness, log IgE | Caucasian (UK) | [S10] | |
Bronchial hyperresponsiveness | Caucasian | [S23] | |
Atopy | Japanese | [S24] | |
Asthma, atopy | Caucasian | [S25] | |
Atopic dermatitis | German | [S26] | |
12q14-24 | Asthma | German/Swedish Caucasian (US) | |
Caucasian (UK) | [S28] | ||
Asthma, atopy | Afro-Caribbean | [S29] | |
Total IgE, asthma | Afro-Caribbean, Amish | [S30] | |
Total IgE | German | [S31] | |
Bronchial hyperresponsiveness | Hutterites | [S3]* | |
Eosinophil count | French | [S7]* | |
13q11-32 | Atopic dermatitis | German/Swedish | [S14] |
Specific IgE | Caucasian (UK) | [S1]* | |
Atopy | Caucasian (Australian) | [S2]* | |
Eosinophil count | French | [S7]* | |
Asthma | Caucasian (US), Japanese | ||
Atopic asthma | Japanese | [S32] |
Candidate gene studies
Chromosomal | Single nucleotide | Phenotype | Functional | |||||
---|---|---|---|---|---|---|---|---|
location | Number* | Molecule | polymorphism/mutation† | related | Population | (in vitro) | Reference | |
1p32 | 1 | Histamine-N- | C314T (Thr105Ile) | Asthma | Caucasian | Yes | [28] | |
methyl-transferase | ||||||||
2q33-34 | 2 | CD28 | T19int3C | None | Caucasian | [S33] | ||
CTLA-4 | A49G | None | Caucasian | [S33] | ||||
C-318T | None | Caucasian | ||||||
3p21 | 3 | CCR5 | CC5-Δ32 | Asthma | Caucasian | Yes | [40] | |
No Association | British/Australian | [41] | ||||||
5q31-34 | 4 | IL-4 | C-590T | Total IgE | Japanese | Yes | [S34] | |
(= C-589T) | Total IgE | American | [S35] | |||||
Specific IgE, wheeze | Australian | [S36] | ||||||
FEV1 | Caucasian | [S37] | ||||||
Atopic dermatitis | Japanese | [S38] | ||||||
None | Caucasian | [S39] | ||||||
C+33T | Total IgE | Japanese | [S40] | |||||
5 | IL-5 | None | Australian | [S41] | ||||
6 | IL-13 | C-1055T | Allergic asthma | Dutch | [S42] | |||
identical | ||||||||
C-1112T | Total IgE | American/German | [19] | |||||
A-1512C | ||||||||
C1923T | ||||||||
G2525A | ||||||||
C2580A | ||||||||
C2749T | ||||||||
Arg130Gln | ||||||||
identical | G4257A | High IgE, atopic dermatitis | German | [S43] | ||||
Gln110Arg | Atopic and intrinsic | British/Japanese | [S44] | |||||
asthma | ||||||||
7 | β2-AR | G-1023A | ||||||
C-709A | ||||||||
G-654A | ||||||||
C-468G | ||||||||
C-406T | ||||||||
T-367C | Drug response | Caucasian/African American | Yes | [24] | ||||
T-47C | (Haplotype studies) | Asian/Hispanic-Latino | ||||||
T-20C | ||||||||
G46A (= Gly16Arg) | ||||||||
C79G (= Gln27Glu) | ||||||||
G252A | ||||||||
C491T (= Thr164Ile) | ||||||||
C523A | ||||||||
Gly16Arg | Drug response | American | Yes | [27] | ||||
FEV1 and FVC | Hutterites | [S45] | ||||||
Asthma severity | Not specified | [S46] | ||||||
Gly16Arg | Nocturnal asthma | American | [25] | |||||
Steroid-dependent asthma | American | [S47] | ||||||
None | German | [S48] | ||||||
Drug response | Not specified | [S49] | ||||||
Gln27Glu | Drug response | American | Yes | [27] | ||||
Drug response | Not specified | [S49] | ||||||
None | German | [S48] | ||||||
Total IgE | Caucasian | [S50] | ||||||
FEV1 | British | [S51] | ||||||
8 | IRF-1 | -300 G/T | None | Japanese | [S52] | |||
4396 A/G | None | |||||||
6355 G/A | None | |||||||
9 | CD14 | -159 C → T | Total IgE | Caucasian | [S53] | |||
None | Hispanic | [S53] | ||||||
Total IgE | British | [S54] | ||||||
None | Japanese | [S54] | ||||||
5q35 | 10 | LTC4 synthase | -444 C | Aspirin-induced asthma | Caucasian | Yes | [30] | |
None | American | No | [S55] | |||||
6p21 | 11 | HLA-II | Specific IgE | Multiple | [S56] | |||
TNF | -308 TNF2 | BHR | Caucasian | [S57] | ||||
LT-α | LT alpha NcoI*1/ | Asthma | British | [S58] | ||||
TNF-308*2 haplotype | ||||||||
-308 TNF1 | Asthma | Australian | [S59] | |||||
LT-alpha*2 | Asthma | |||||||
6p21-12 | 24 | PAF-acetyl-hydrolase | Ile198Thr | Atopic Asthma/ | German/British | Yes | [S60] | |
total IgE | ||||||||
Ala379Val | Asthma/specific IgE | Yes | ||||||
Arg92His | None | Yes | ||||||
10 | 12 | 5-LO (promoter) | (GGGCGG)n = 3–6 | Drug Response | Not specified | Yes | [29] | |
11q12-13 | 14 | CC16 | A38G | Asthma | Australian | [S61] | ||
None | British/Japanese | [S62] | ||||||
15 | FcεR1-β | lle181Leu | Atopy | British | No | [S63] | ||
Japanese | [S64] | |||||||
Leu181/Leu183 | Atopy, BHR | British/Australian | No | [S65] | ||||
None | Australian | [S51] | ||||||
E237G (= Gly237Glu) | Atopy | Australian | No | [S66] | ||||
None | Japanese | [S67] | ||||||
RsaI_in2*B | Asthma | Australian | [S68] | |||||
RsaI_ex7 (+ RsaI_in2*B) | Total IgE, atopic | Not specified | [S69] | |||||
dermatitis, asthma | ||||||||
-109C/T | Total IgE | Japanese | [S70] | |||||
13 | GSTP1 | Ile105Val | IgE/Skin Test/FEV1 | Caucasian | [S71] | |||
12q13 | 17 | STAT6 | G2964A | Asthma | Japanese | [S72] | ||
12q14 | 16 | IFN-γ | None | Australian/Venezuelan | [S73] | |||
12q24 | 18 | NO-synthase 1 | (AAT)n ≥ 12 | Exhaled NO | Mixed | [S74] | ||
14p11 | 19 | TCR | VA8.1(*)2 | Specific IgE | Caucasian | [S75] | ||
20 | Mast cell chymase | MCC BstXI | Eczema | Japanese | [S76] | |||
Total IgE | Not specified | [S77] | ||||||
None | Japanese | [S78] | ||||||
None | Italian | [S79] | ||||||
Atopic dermatitis | Japanese | [S80] | ||||||
With high IgE | ||||||||
16p12-p11 | 21 | IL-4Rα | Q576R (= Arg551Gln) | Atopy, high IgE | American | Yes | [S81] | |
Asthma severity (FEV1) | American | [S82] | ||||||
None | Italian | [S83] | ||||||
Atopic dermatitis | Japanese | [S84] | ||||||
Low IgE | German | Yes | [20] | |||||
S503P (= 478Pro) | Low IgE | [20] | ||||||
E400A | None | |||||||
C431R | None | |||||||
Ile50Val | IgE/atopic asthma | Japanese | Yes | [S85] | ||||
None | Japanese | [S86] | ||||||
Ile50Val | ||||||||
Ser727Ala | ||||||||
Glu375Ala | ||||||||
Cys406Arg | Atopy/asthma | Hutterites/Caucasian | [21] | |||||
Ser411Leu | (Haplotype studies) | African American/Hispanic | ||||||
Ser761Pro | ||||||||
Ser478Pro | ||||||||
Gln551Arg | ||||||||
17q11-q12 | 22 | RANTES | G-401A | Atopic dermatitis | Caucasian | Yes | [43] | |
identical | ||||||||
G-403A | Asthma, atopy | Caucasian | [44] | |||||
Xq | 23 | IL-13Rα1 | A1398G | Total IgE | British | [S44] |