|
|
Science 22 December 2000:
Vol. 290. no. 5500, pp. 2304 - 2305
DOI: 10.1126/science.290.5500.2304
|
|
|
Susceptibility Locus for Alzheimer's Disease on Chromosome 10
Amanda Myers, Peter Holmans, Helen Marshall, Jennifer Kwon, David Meyer, Dzanan Ramic, Shantia Shears,
Jeremy Booth, Fabienne Wavrant DeVrieze, Richard Crook, Marian Hamshere, Richard Abraham, Nigel
Tunstall, Francis Rice, Stephanie Carty, Sara Lillystone, Pat Kehoe, Varuni Rudrasingham, Lesley Jones, Simon
Lovestone, Jordi Perez-Tur, Julie Williams, Michael J. Owen, John Hardy, and Alison M. Goate
|
Supplementary Material
| Supplemental Table 1. Numbers of families and sib-pairs for each stage of the genome screen. APOE4 positive affected sib-pairs (APOE4+ve ASPs) are sib-pairs in which each sib has at least one E4+ allele, APOE4 negative ASPs (APOE4-ves) are sib-pairs in which neither sib possesses an E4 allele. 266 ASPs are from the NIMH AD Genetics Initiative (5), 80 ASPs are from the NIA Indiana Alzheimer's Disease National Cell repository (NIA grant #P30 AG10133) and 83 ASPs were collected in the UK for this project. Autopsy confirmation of AD was available in at least one individual from 193 families (NIMH=119, IADC=74). The 266 ASPs from the NIMH Genetics Initiative, overlap with the families used in the accompanying paper (224/238 families and 564/598 individuals in our study were also used in the Bertram et al., study (14)). |
| # OF
SIBSHIPS* | MEAN AGE
OF ONSET | TOTAL #
ASPS | # APOE4+
ASPS | # APOE4-
ASPS |
| STAGE 1 | 211 | 75 | 261 | 149 | 56 |
| | | | | |
| STAGE 2 | 342 | 75 | 429 | 262 | 83 |
| | | | | |
| *NUMBER OF SIBSHIPS WITH TWO OR MORE TYPED AFFECTED SIBS |
| Supplemental Table 2. Two-point lodscores and IBD sharing probabilities for chromosome 10 markers.
Stage 1 markers are shown in blue and stage 2 markers are shown in black. Results for D10S1211 are highlighted in bold. Position in cM from pter of chromosome 10, Het.= marker heterozygosity, # of Families and sibpairs.= number of families/sibpairs typed for that marker. . Gray box indicates ten markers with elevated lodscores and increased allele sharing flanking D10S1211. Six of these ten markers (D10S1426, D10S1220, D10S1225, D10S1211, D10S1670, D10S2475) give lodscores >1 in the whole sample, and all ten markers show elevated allele sharing in the same sample. When the sample is stratified by APOE genotype, six of these markers (D10S1220, D10S1225, D10S1211, D10S1670, D10S2327, D10S2475) also give lodscores >1 and nine of them show elevated IBD sharing in the APOE4 positive sib-pairs. In contrast, negligible lodscores are obtained in the APOE negative sib-pairs with all markers in this region except D10S1211 (lodscore =1.11), although five of the ten markers do show elevated IBD sharing. |
| LOCUS | POSITION | HET. | NO. OF
FAMILIES | NO. OF
SIBPAIRS | WHOLE SAMPLE
IBD LOD | APOE 4 +VES
IBD LOD | APOE 4 -VES
IBD LOD |
|---|
| 591 | 13.49 | 0.76 | 186 | 232 | 0.5 | 0 | 0.51 | 0.006 | 0.5 | 0 |
| 1216 | 30 | 0.76 | 207 | 247 | 0.53 | 0.34 | 0.56 | 0.62 | 0.5 | 0 |
| 1423 | 47.45 | 0.77 | 193 | 241 | 0.5 | 0 | 0.5 | 0 | 0.5 | 0 |
| 1426 | 59.03 | 0.75 | 316 | 391 | 0.55 | 1.12 | 0.54 | 0.57 | 0.55 | 0.21 |
| 1217 | 63.83 | 0.48 | 293 | 359 | 0.56 | 0.76 | 0.57 | 0.68 | 0.5 | 0 |
| 1220 | 70.23 | 0.6 | 285 | 356 | 0.6 | 2.12 | 0.64 | 2.89 | 0.5 | 0 |
| 1227 | 75.57 | 0.72 | 301 | 365 | 0.56 | 0.96 | 0.53 | 0.22 | 0.57 | 0.19 |
| 1225 | 80.77 | 0.76 | 283 | 349 | 0.56 | 1.54 | 0.58 | 1.37 | 0.56 | 0.17 |
| 1211 | 82.21 | 0.65 | 310 | 387 | 0.64 | 4.85 | 0.64 | 3.83 | 0.69 | 1.11 |
| 1670 | 86.2 | 0.75 | 325 | 406 | 0.57 | 1.79 | 0.61 | 2.25 | 0.58 | 0.44 |
| 676 | 90.01 | 0.79 | 307 | 373 | 0.55 | 0.95 | 0.55 | 0.63 | 0.54 | 0.08 |
| 2327 | 100.92 | 0.77 | 331 | 398 | 0.55 | 0.68 | 0.56 | 1.01 | 0.5 | 0 |
| 2475 | 103.43 | 0.87 | 326 | 408 | 0.56 | 1.42 | 0.57 | 1.34 | 0.54 | 0.13 |
| 1765 | 108.79 | 0.83 | 326 | 402 | 0.53 | 0.44 | 0.56 | 0.97 | 0.5 | 0 |
| 2470 | 112.58 | 0.83 | 316 | 387 | 0.52 | 0.23 | 0.52 | 0.1 | 0.54 | 0.22 |
| 677 | 117.42 | 0.81 | 332 | 409 | 0.53 | 0.52 | 0.56 | 0.81 | 0.51 | 0.01 |
| 1265 | 124.27 | 0.83 | 330 | 414 | 0.53 | 0.61 | 0.53 | 0.21 | 0.58 | 0.71 |
| 670 | 126.5 | 0.52 | 296 | 367 | 0.53 | 0.17 | 0.51 | 0.01 | 0.69 | 1.75 |
| 1246 | 128.73 | 0.81 | 316 | 386 | 0.54 | 0.57 | 0.54 | 0.33 | 0.54 | 0.13 |
| 1269 | 131.8 | 0.61 | 326 | 403 | 0.5 | 0 | 0.5 | 0 | 0.5 | 0 |
| 187 | 135.24 | 0.8 | 288 | 352 | 0.53 | 0.31 | 0.52 | 0.1 | 0.53 | 0.06 |
| 610 | 138.94 | 0.56 | 194 | 240 | 0.54 | 0.3 | 0.57 | 0.47 | 0.5 | 0 |
| 1213 | 148.17 | 0.8 | 167 | 202 | 0.52 | 0.15 | 0.5 | 0 | 0.5 | 0 |
|
|
