Background
Methods
Family screening
DNA extraction and genotyping
Power studies
Linkage analysis
Model | Allele Frequency | Penetrance in DD:Dd susceptibility allele carriers | Penetrance in dd normal homozygotes |
---|---|---|---|
1 | 0.0133 | 0.90 | 0.00 |
2 | 0.0133 | 0.80 | 0.00 |
3 | 0.0133 | 0.80 | 0.05 |
4 | 0.0133 | 0.60 | 0.15 |
5 | 0.05 | 0.90 | 0.00 |
6 | 0.05 | 0.80 | 0.00 |
7 | 0.05 | 0.80 | 0.05 |
8 | 0.05 | 0.60 | 0.15 |
9 | 0.10 | 0.90 | 0.00 |
10 | 0.10 | 0.80 | 0.00 |
11 | 0.10 | 0.80 | 0.05 |
12 | 0.10 | 0.60 | 0.15 |
Results
Power simulation
PENETRANCE IN DD:Dd SUSC. ALLELE CARRIERS | PENETRANCE IN dd NORMAL HOMOZYGOTE | % FAMILIES LINKED | |||||||
---|---|---|---|---|---|---|---|---|---|
100% | 75% | 50% | 25% | ||||||
Power1
| ELod ± s.d.2
| Power1
| ELod ± s.d.2
| Power1
| ELod ± s.d.2
| Power1
| ELod ± s.d.2
| ||
0.8 | 0.08 | 100 | 14.0 ± 0.3 | 99 | 8.9 ± 0.3 | 82 | 4.7 ± 0.2 | 18 | 1.7 ± 0.1 |
0.8 | 0.15 | 100 | 14.7 ± 0.3 | 100 | 9.1 ± 0.3 | 73 | 4.8 ± 0.2 | 14 | 1.6 ± 0.1 |
0.7 | 0.08 | 100 | 14.8 ± 0.3 | 99 | 8.5 ± 0.3 | 77 | 4.8 ± 0.2 | 17 | 1.8 ± 0.15 |
0.7 | 0.15 | 100 | 15.2 ± 0.3 | 99 | 8.8 ± 0.3 | 70 | 4.5 ± 0.2 | 14 | 1.6 ± 0.1 |
0.6 | 0.08 | 100 | 15.0 ± 0.3 | 98 | 8.6 ± 0.25 | 67 | 4.3 ± 0.2 | 14 | 1.7 ± 0.1 |
0.6 | 0.15 | 100 | 14.2 ± 0.3 | 100 | 8.4 ± 0.3 | 73 | 4.3 ± 0.2 | 5 | 1.2 ± 0.1 |
Linkage
Two-point linkage analyses in the Amish and Jewish populations
RECOMBINATION FRACTION, θ | |||||||
---|---|---|---|---|---|---|---|
MARKER | 0.0 | 0.01 | 0.05 | 0.1 | 0.2 | 0.3 | 0.4 |
D12S85 | -19.55 | -12.97 | -9.02 | -6.27 | -2.92 | -1.15 | -0.31 |
D12S1706 | -39.91 | -29.33 | -17.82 | -10.79 | -3.85 | -1.06 | -0.18 |
D12S346 | -36.18 | -24.54 | -13.68 | -7.57 | -1.99 | -0.14 | 0.08 |
D12S78 | -40.39 | -28.61 | -17.98 | -11.46 | -4.57 | -1.5 | -0.33 |
D12S79 | -49.21 | -32.42 | -19.78 | -12.36 | -4.82 | -1.5 | -0.2 |
D12S86 | -40.95 | -32.39 | -20.01 | -12.52 | -5.14 | -1.85 | -0.43 |
D18S59 | -26.98 | -20.07 | -11.74 | -6.77 | -2.2 | -0.48 | -0.02 |
D18S481 | -29.61 | -19.93 | -11.02 | -5.99 | -1.42 | -0.04 | 0.16 |
D18S63 | -32.32 | -23.1 | -12.11 | -5.98 | -0.87 | 0.5 | 0.35 |
D18S452 | -38.37 | -27.85 | -16.16 | -9.31 | -2.76 | -0.35 | 0.15 |
D18S53 | -35.69 | -25.42 | -15.08 | -9.07 | -3.22 | -0.77 | -0.01 |
D18S474 | -26.64 | -14.04 | -5.89 | -2.01 | 0.94 | 1.39 | 0.7 |
RECOMBINATION FRACTION, θ | |||||||
---|---|---|---|---|---|---|---|
MARKER | 0 | 0.01 | 0.05 | 0.1 | 0.2 | 0.3 | 0.4 |
D12S85 | -7.5 | -6.71 | -4.62 | -2.56 | -0.44 | 0.19 | 0.17 |
D12S1706 | -36.21 | -28.66 | -17.67 | -10.77 | -3.85 | -1.04 | -0.15 |
D12S346 | -32.76 | -24.46 | -13.34 | -7.11 | -1.68 | -0.04 | 0.11 |
D12S78 | -27.99 | -20.59 | -10.1 | -4.65 | -0.46 | 0.43 | 0.24 |
D12S79 | -38.53 | -30.26 | -18.47 | -11.21 | -4.12 | -1.24 | -0.26 |
D12S86 | -39.59 | -31.68 | -19.83 | -12.58 | -5.12 | -1.8 | -0.45 |
D18S59 | -35.34 | -27.25 | -16.82 | -10.69 | -4.4 | -1.51 | -0.26 |
D18S481 | -32.69 | -24 | -14.58 | -9.19 | -3.73 | -1.26 | -0.24 |
D18S63 | -36.39 | -28.55 | -17.92 | -11.36 | -4.65 | -1.63 | -0.35 |
D18S452 | -34.97 | -25.21 | -15.47 | -9.72 | -3.78 | -1.22 | -0.23 |
D18S53 | -38.03 | -26.36 | -14.65 | -8.62 | -3.15 | -0.94 | -0.14 |
D18S474 | -29.88 | -22.79 | -14.41 | -9.29 | -3.98 | -1.45 | -0.31 |
Multipoint linkage analyses in the Amish and Jewish populations
Individual families showing linkage
AMISH FAMILIES | |||||
---|---|---|---|---|---|
FAMILY ID | TWO-POINT LOD | MULTIPOINT | |||
Marker | Zmax | LOD | NPL | P value | |
3061 | D12S1706 | 1.04 | 1.04 | * | N/A |
D12S346 | 1.04 | 1.04 | * | N/A | |
D12S78 | 1.04 | 1.04 | * | N/A | |
3049 | D18S474 | 1.14 | 1.27 | 2.19 | 0.02 |
3053 | D18S474 | 1.30 | 1.30 | -* | N/A |
3064 | D18S63 | 1.30 | 1.30 | -* | N/A |
JEWISH FAMILIES | |||||
FAMILY ID | TWO-POINT LOD | MULTIPOINT | |||
Marker | Zmax | LOD | NPL | P value | |
20 | D12S79 | 1.12 | 1.12 | 3.45 | 0.02 |
D12S86 | 1.12 | 1.12 | 3.45 | 0.02 | |
58 | D12S1706 | 1.16 | 1.16 | 3.01 | 0.06 |
D12S346 | 1.16 | 1.16 | 3.01 | 0.06 | |
78 | D12S85 | 1.07 | 1.07 | 3.38 | 0.01 |