Selection of somatic escape variants in SERPINA1 in liver tissue of patients with alpha-1 anti-trypsin deficiency - Exome
Somatic variants accumulate in non-malignant tissues with age. Functional variants leading to clonal advantage of hepatocytes accumulate in the liver from patients with acquired chronic liver disease (CLD). Whether somatic variants are common to CLD from differing aetiologies is unknown. We analysed liver somatic variants in patients with genetic CLD from alpha-1 anti-trypsin (A1AT) deficiency or haemochromatosis. We show that somatic variants in SERPINA1, the gene encoding A1AT, are strongly selected for in A1AT deficiency, with evidence of convergent evolution. Acquired SERPINA1 variants are clustered leading to truncation or coding change at the C-terminus of A1AT. In vitro and in vivo, C-terminal truncation variants reduce disease-associated Z-A1AT polymer accumulation and disruption of the endoplasmic reticulum, supporting the C-terminal domain swap mechanism. Therefore, somatic escape variants from a deleterious germline variant are selected for in A1AT deficiency, suggesting functional somatic variants are disease-specific in CLD and point to disease-associated mechanisms.
- 1 sample
- DAC: EGAC00001000000
- Technology: Illumina NovaSeq 6000
- PUB DUO:0000019 (version: 2021-02-23)publication requiredThis data use modifier indicates that requestor agrees to make results of studies using the data available to the larger scientific community.
- US DUO:0000026 (version: 2021-02-23)user specific restrictionThis data use modifier indicates that use is limited to use by approved users.
- IS DUO:0000028 (version: 2021-02-23)institution specific restrictionThis data use modifier indicates that use is limited to use within an approved institution.
- GRU DUO:0000042 (version: 2021-02-23)general research useThis data use permission indicates that use is allowed for general research use for any research purpose.
Wellcome Trust Sanger Institute Cancer Genome Group Data Sharing Policy
Studies are experimental investigations of a particular phenomenon, e.g., case-control studies on a particular trait or cancer research projects reporting matching cancer normal genomes from patients.
Study ID | Study Title | Study Type |
---|---|---|
EGAS00001005158 | Other |
This table displays only public information pertaining to the files in the dataset. If you wish to access this dataset, please submit a request. If you already have access to these data files, please consult the download documentation.
ID | File Type | Size | Located in | |
---|---|---|---|---|
EGAF00008611181 | cram | 3.9 GB | ||
EGAF00008611182 | cram | 3.2 GB | ||
EGAF00008611183 | cram | 3.0 GB | ||
EGAF00008611184 | cram | 2.7 GB | ||
EGAF00008611185 | cram | 3.3 GB | ||
EGAF00008611186 | cram | 3.5 GB | ||
EGAF00008611187 | cram | 4.1 GB | ||
EGAF00008611188 | cram | 3.3 GB | ||
EGAF00008611189 | cram | 3.2 GB | ||
EGAF00008611190 | cram | 3.4 GB | ||
EGAF00008611191 | cram | 3.4 GB | ||
EGAF00008611192 | cram | 4.1 GB | ||
EGAF00008611193 | cram | 2.9 GB | ||
EGAF00008611194 | cram | 2.5 GB | ||
EGAF00008611195 | cram | 3.5 GB | ||
EGAF00008611196 | cram | 3.9 GB | ||
EGAF00008611197 | cram | 3.2 GB | ||
EGAF00008611198 | cram | 4.4 GB | ||
EGAF00008611199 | cram | 3.4 GB | ||
EGAF00008611200 | cram | 3.8 GB | ||
EGAF00008611201 | cram | 3.8 GB | ||
EGAF00008611202 | cram | 4.1 GB | ||
EGAF00008611203 | cram | 2.1 GB | ||
EGAF00008611204 | cram | 3.5 GB | ||
EGAF00008611205 | cram | 3.3 GB | ||
EGAF00008611206 | cram | 4.3 GB | ||
EGAF00008611207 | cram | 3.2 GB | ||
EGAF00008611208 | cram | 3.1 GB | ||
EGAF00008611209 | cram | 3.4 GB | ||
EGAF00008611210 | cram | 3.0 GB | ||
EGAF00008611211 | cram | 2.8 GB | ||
EGAF00008611212 | cram | 3.7 GB | ||
EGAF00008611213 | cram | 3.2 GB | ||
EGAF00008611214 | cram | 3.4 GB | ||
EGAF00008611215 | cram | 2.6 GB | ||
EGAF00008611216 | cram | 2.9 GB | ||
EGAF00008611217 | cram | 3.1 GB | ||
EGAF00008611218 | cram | 4.9 GB | ||
EGAF00008611219 | cram | 4.3 GB | ||
EGAF00008611220 | cram | 2.8 GB | ||
EGAF00008611221 | cram | 4.2 GB | ||
EGAF00008611222 | cram | 3.7 GB | ||
EGAF00008611223 | cram | 3.6 GB | ||
EGAF00008611224 | cram | 3.2 GB | ||
EGAF00008611225 | cram | 3.5 GB | ||
EGAF00008611226 | cram | 2.2 GB | ||
EGAF00008611227 | cram | 3.4 GB | ||
EGAF00008611228 | cram | 3.1 GB | ||
EGAF00008611229 | cram | 2.6 GB | ||
EGAF00008611230 | cram | 2.4 GB | ||
EGAF00008611231 | cram | 3.1 GB | ||
EGAF00008611232 | cram | 3.9 GB | ||
EGAF00008611233 | cram | 3.8 GB | ||
EGAF00008611234 | cram | 3.3 GB | ||
EGAF00008611235 | cram | 2.8 GB | ||
EGAF00008611236 | cram | 2.6 GB | ||
EGAF00008611237 | cram | 3.4 GB | ||
EGAF00008611238 | cram | 3.2 GB | ||
EGAF00008611239 | cram | 3.4 GB | ||
EGAF00008611240 | cram | 4.0 GB | ||
EGAF00008611241 | cram | 2.9 GB | ||
EGAF00008611242 | cram | 2.5 GB | ||
EGAF00008611243 | cram | 4.2 GB | ||
EGAF00008611244 | cram | 3.3 GB | ||
EGAF00008611245 | cram | 2.4 GB | ||
EGAF00008611246 | cram | 2.5 GB | ||
EGAF00008611247 | cram | 3.3 GB | ||
EGAF00008611248 | cram | 3.2 GB | ||
EGAF00008611249 | cram | 2.9 GB | ||
EGAF00008611250 | cram | 2.5 GB | ||
EGAF00008611251 | cram | 3.2 GB | ||
EGAF00008611252 | cram | 3.9 GB | ||
EGAF00008611253 | cram | 3.2 GB | ||
EGAF00008611254 | cram | 2.0 GB | ||
EGAF00008611255 | cram | 1.7 GB | ||
EGAF00008611256 | cram | 3.2 GB | ||
EGAF00008611257 | cram | 2.7 GB | ||
EGAF00008611258 | cram | 1.9 GB | ||
EGAF00008611259 | cram | 2.5 GB | ||
EGAF00008611260 | cram | 3.8 GB | ||
EGAF00008611261 | cram | 3.2 GB | ||
EGAF00008611262 | cram | 2.8 GB | ||
EGAF00008611263 | cram | 2.7 GB | ||
EGAF00008611264 | cram | 3.9 GB | ||
EGAF00008611265 | cram | 3.8 GB | ||
EGAF00008611266 | cram | 2.7 GB | ||
EGAF00008611267 | cram | 4.2 GB | ||
EGAF00008611268 | cram | 3.1 GB | ||
EGAF00008611269 | cram | 2.4 GB | ||
EGAF00008611270 | cram | 2.8 GB | ||
EGAF00008611271 | cram | 3.4 GB | ||
EGAF00008611272 | cram | 2.6 GB | ||
EGAF00008611273 | cram | 3.3 GB | ||
EGAF00008611274 | cram | 4.1 GB | ||
EGAF00008611275 | cram | 2.9 GB | ||
EGAF00008611276 | cram | 3.1 GB | ||
EGAF00008611277 | cram | 3.8 GB | ||
EGAF00008611278 | cram | 2.4 GB | ||
EGAF00008611279 | cram | 3.3 GB | ||
EGAF00008611280 | cram | 3.5 GB | ||
EGAF00008611281 | cram | 3.5 GB | ||
EGAF00008611282 | cram | 3.4 GB | ||
EGAF00008611283 | cram | 2.9 GB | ||
EGAF00008611284 | cram | 3.6 GB | ||
EGAF00008611285 | cram | 2.4 GB | ||
EGAF00008611286 | cram | 3.1 GB | ||
EGAF00008611287 | cram | 3.6 GB | ||
EGAF00008611288 | cram | 3.6 GB | ||
EGAF00008611289 | cram | 3.3 GB | ||
EGAF00008611290 | cram | 3.0 GB | ||
EGAF00008611291 | cram | 3.4 GB | ||
EGAF00008611292 | cram | 3.7 GB | ||
EGAF00008611293 | cram | 4.7 GB | ||
EGAF00008611294 | cram | 2.9 GB | ||
EGAF00008611295 | cram | 3.4 GB | ||
EGAF00008611296 | cram | 3.2 GB | ||
EGAF00008611297 | cram | 2.5 GB | ||
EGAF00008611298 | cram | 3.6 GB | ||
EGAF00008611299 | cram | 3.9 GB | ||
EGAF00008611300 | cram | 3.2 GB | ||
EGAF00008611301 | cram | 3.0 GB | ||
EGAF00008611302 | cram | 2.9 GB | ||
EGAF00008611303 | cram | 3.4 GB | ||
EGAF00008611304 | cram | 2.0 GB | ||
EGAF00008611305 | cram | 3.0 GB | ||
EGAF00008611306 | cram | 2.6 GB | ||
EGAF00008611307 | cram | 3.4 GB | ||
EGAF00008611308 | cram | 2.3 GB | ||
EGAF00008611309 | cram | 4.0 GB | ||
EGAF00008611310 | cram | 3.7 GB | ||
EGAF00008611311 | cram | 2.6 GB | ||
EGAF00008611312 | cram | 2.8 GB | ||
EGAF00008611313 | cram | 2.8 GB | ||
EGAF00008611314 | cram | 3.4 GB | ||
EGAF00008611315 | cram | 3.6 GB | ||
EGAF00008611316 | cram | 2.6 GB | ||
EGAF00008611317 | cram | 2.4 GB | ||
EGAF00008611318 | cram | 3.3 GB | ||
EGAF00008611319 | cram | 2.8 GB | ||
EGAF00008611320 | cram | 3.3 GB | ||
EGAF00008611321 | cram | 3.8 GB | ||
EGAF00008611322 | cram | 3.4 GB | ||
EGAF00008611323 | cram | 3.3 GB | ||
EGAF00008611324 | cram | 3.0 GB | ||
EGAF00008611325 | cram | 3.2 GB | ||
EGAF00008611326 | cram | 3.1 GB | ||
EGAF00008611327 | cram | 3.4 GB | ||
EGAF00008611328 | cram | 3.1 GB | ||
EGAF00008611329 | cram | 2.7 GB | ||
EGAF00008611330 | cram | 4.7 GB | ||
EGAF00008611331 | cram | 3.2 GB | ||
EGAF00008611332 | cram | 3.8 GB | ||
EGAF00008611333 | cram | 2.1 GB | ||
EGAF00008611334 | cram | 3.3 GB | ||
EGAF00008611335 | cram | 2.5 GB | ||
EGAF00008611336 | cram | 3.1 GB | ||
EGAF00008611337 | cram | 2.5 GB | ||
EGAF00008611338 | cram | 2.9 GB | ||
EGAF00008611339 | cram | 2.8 GB | ||
EGAF00008611340 | cram | 2.4 GB | ||
EGAF00008611341 | cram | 2.5 GB | ||
EGAF00008611342 | cram | 3.0 GB | ||
EGAF00008611343 | cram | 3.3 GB | ||
EGAF00008611344 | cram | 2.7 GB | ||
EGAF00008611345 | cram | 3.0 GB | ||
EGAF00008611346 | cram | 3.3 GB | ||
EGAF00008611347 | cram | 2.3 GB | ||
EGAF00008611348 | cram | 2.9 GB | ||
EGAF00008611349 | cram | 3.3 GB | ||
EGAF00008611350 | cram | 3.2 GB | ||
EGAF00008611351 | cram | 2.9 GB | ||
EGAF00008611352 | cram | 2.8 GB | ||
EGAF00008611353 | cram | 3.4 GB | ||
EGAF00008611354 | cram | 2.6 GB | ||
EGAF00008611355 | cram | 2.4 GB | ||
EGAF00008611356 | cram | 2.9 GB | ||
EGAF00008611357 | cram | 2.7 GB | ||
EGAF00008611358 | cram | 2.7 GB | ||
EGAF00008611359 | cram | 2.6 GB | ||
EGAF00008611360 | cram | 2.6 GB | ||
EGAF00008611361 | cram | 2.8 GB | ||
EGAF00008611362 | cram | 2.9 GB | ||
EGAF00008611363 | cram | 3.1 GB | ||
EGAF00008611364 | cram | 2.7 GB | ||
EGAF00008611365 | cram | 2.4 GB | ||
EGAF00008611366 | cram | 2.9 GB | ||
EGAF00008611367 | cram | 2.3 GB | ||
EGAF00008611368 | cram | 3.0 GB | ||
EGAF00008611369 | cram | 2.2 GB | ||
EGAF00008611370 | cram | 2.8 GB | ||
EGAF00008611371 | cram | 2.3 GB | ||
EGAF00008611372 | cram | 2.2 GB | ||
EGAF00008611373 | cram | 2.2 GB | ||
EGAF00008611374 | cram | 2.8 GB | ||
EGAF00008611375 | cram | 3.0 GB | ||
EGAF00008611376 | cram | 2.5 GB | ||
EGAF00008611377 | cram | 3.2 GB | ||
EGAF00008611378 | cram | 2.8 GB | ||
EGAF00008611379 | cram | 2.6 GB | ||
EGAF00008611380 | cram | 2.6 GB | ||
EGAF00008611381 | cram | 2.4 GB | ||
EGAF00008611382 | cram | 2.6 GB | ||
EGAF00008611383 | cram | 4.2 GB | ||
EGAF00008611384 | cram | 3.6 GB | ||
EGAF00008611385 | cram | 4.5 GB | ||
EGAF00008611386 | cram | 3.7 GB | ||
EGAF00008611387 | cram | 4.1 GB | ||
EGAF00008611388 | cram | 3.4 GB | ||
EGAF00008611389 | cram | 3.8 GB | ||
EGAF00008611390 | cram | 3.4 GB | ||
EGAF00008611391 | cram | 4.0 GB | ||
EGAF00008611392 | cram | 3.7 GB | ||
EGAF00008611393 | cram | 4.4 GB | ||
EGAF00008611394 | cram | 3.8 GB | ||
EGAF00008611395 | cram | 4.3 GB | ||
EGAF00008611396 | cram | 5.0 GB | ||
EGAF00008611397 | cram | 4.2 GB | ||
EGAF00008611398 | cram | 3.7 GB | ||
EGAF00008611399 | cram | 3.8 GB | ||
EGAF00008611400 | cram | 4.0 GB | ||
EGAF00008611401 | cram | 3.4 GB | ||
EGAF00008611402 | cram | 4.2 GB | ||
EGAF00008611403 | cram | 3.7 GB | ||
EGAF00008611404 | cram | 3.8 GB | ||
EGAF00008611405 | cram | 3.7 GB | ||
EGAF00008611406 | cram | 4.1 GB | ||
EGAF00008611407 | cram | 4.6 GB | ||
EGAF00008611408 | cram | 4.8 GB | ||
EGAF00008611409 | cram | 4.3 GB | ||
EGAF00008611410 | cram | 3.7 GB | ||
EGAF00008611411 | cram | 3.7 GB | ||
EGAF00008611412 | cram | 3.9 GB | ||
EGAF00008611413 | cram | 4.1 GB | ||
EGAF00008611414 | cram | 4.5 GB | ||
234 Files (756.0 GB) |