PubMed:28934397
Annnotations
PubMed_ArguminSci
| Id | Subject | Object | Predicate | Lexical cue |
|---|---|---|---|---|
| T1 | 60-178 | DRI_Background | denotes | Huntington's disease (HD) is a dominantly inherited neurodegenerative disease caused by an expanded CAG repeat in HTT. |
| T2 | 179-295 | DRI_Background | denotes | Many clinical characteristics of HD such as age at motor onset are determined largely by the size of HTT CAG repeat. |
| T3 | 296-440 | DRI_Challenge | denotes | However, emerging evidence strongly supports a role for other genetic factors in modifying the disease pathogenesis driven by mutant huntingtin. |
| T4 | 441-649 | DRI_Background | denotes | A recent genome-wide association analysis to discover genetic modifiers of HD onset age provided initial evidence for modifier loci on chromosomes 8 and 15 and suggestive evidence for a locus on chromosome 3. |
| T5 | 650-976 | DRI_Approach | denotes | Here, genotyping of candidate single nucleotide polymorphisms in a cohort of 3,314 additional HD subjects yields independent confirmation of the former two loci and moves the third to genome-wide significance at MLH1, a locus whose mouse orthologue modifies CAG length-dependent phenotypes in a Htt-knock-in mouse model of HD. |
| T6 | 977-1169 | DRI_Outcome | denotes | Both quantitative and dichotomous association analyses implicate a functional variant on ∼32% of chromosomes with the beneficial modifier effect that delays HD motor onset by 0.7 years/allele. |
| T7 | 1170-1410 | DRI_Background | denotes | Genomic DNA capture and sequencing of a modifier haplotype localize the functional variation to a 78 kb region spanning the 3'end of MLH1 and the 5'end of the neighboring LRRFIP2, and marked by an isoleucine-valine missense variant in MLH1. |
| T8 | 1411-1609 | DRI_Outcome | denotes | Analysis of expression Quantitative Trait Loci (eQTLs) provides modest support for altered regulation of MLH1 and LRRFIP2, raising the possibility that the modifier affects regulation of both genes. |
| T9 | 1610-1803 | DRI_Outcome | denotes | Finally, polygenic modification score and heritability analyses suggest the existence of additional genetic modifiers, supporting expanded, comprehensive genetic analysis of larger HD datasets. |
c_corpus
| Id | Subject | Object | Predicate | Lexical cue |
|---|---|---|---|---|
| T5 | 14-34 | D006816 | denotes | Huntington's disease |
| T6 | 14-34 | D006816 | denotes | Huntington's disease |
| T9 | 48-52 | PR:Q9ZRV4 | denotes | MLH1 |
| T10 | 48-52 | PR:P38920 | denotes | MLH1 |
| T11 | 48-52 | PR:Q54KD8 | denotes | MLH1 |
| T13 | 48-52 | PR:Q9JK91 | denotes | MLH1 |
| T14 | 48-52 | PR:P97679 | denotes | MLH1 |
| T15 | 48-52 | PR:Q9P7W6 | denotes | MLH1 |
| T16 | 48-52 | PR:000010442 | denotes | MLH1 |
| T17 | 48-52 | PR:P40692 | denotes | MLH1 |
| T12 | 48-52 | CVCL_G669 | denotes | MLH1 |
| T18 | 73-80 | D004194 | denotes | disease |
| T19 | 73-80 | D004194 | denotes | disease |
| T22 | 112-137 | D019636 | denotes | neurodegenerative disease |
| T23 | 112-137 | D019636 | denotes | neurodegenerative disease |
| T26 | 160-163 | CVCL_D569 | denotes | CAG |
| T27 | 164-170 | SO:0001068 | denotes | repeat |
| T28 | 174-177 | PR:P51111 | denotes | HTT |
| T29 | 174-177 | PR:000015189 | denotes | HTT |
| T30 | 174-177 | PR:Q76P24 | denotes | HTT |
| T31 | 174-177 | PR:P31645 | denotes | HTT |
| T32 | 174-177 | PR:P42859 | denotes | HTT |
| T33 | 174-177 | PR:Q60857 | denotes | HTT |
| T34 | 174-177 | PR:P42858 | denotes | HTT |
| T35 | 174-177 | PR:000008840 | denotes | HTT |
| T36 | 280-283 | PR:P51111 | denotes | HTT |
| T37 | 280-283 | PR:000015189 | denotes | HTT |
| T38 | 280-283 | PR:Q76P24 | denotes | HTT |
| T39 | 280-283 | PR:P31645 | denotes | HTT |
| T40 | 280-283 | PR:P42859 | denotes | HTT |
| T41 | 280-283 | PR:Q60857 | denotes | HTT |
| T42 | 280-283 | PR:P42858 | denotes | HTT |
| T43 | 280-283 | PR:000008840 | denotes | HTT |
| T44 | 284-287 | CVCL_D569 | denotes | CAG |
| T45 | 288-294 | SO:0001068 | denotes | repeat |
| T46 | 391-398 | D004194 | denotes | disease |
| T47 | 391-398 | D004194 | denotes | disease |
| T48 | 399-411 | GO:0009405 | denotes | pathogenesis |
| T49 | 429-439 | P42858 | denotes | huntingtin |
| T50 | 429-439 | P42859 | denotes | huntingtin |
| T51 | 429-439 | P51111 | denotes | huntingtin |
| T52 | 429-439 | PR:000008840 | denotes | huntingtin |
| T53 | 429-439 | P51112 | denotes | huntingtin |
| T54 | 450-456 | SO:0001026 | denotes | genome |
| T55 | 636-646 | GO:0005694 | denotes | chromosome |
| T56 | 636-646 | SO:0000340 | denotes | chromosome |
| T57 | 687-697 | CHEBI:36976 | denotes | nucleotide |
| T58 | 717-723 | CHEBI:34935 | denotes | cohort |
| T59 | 834-840 | SO:0001026 | denotes | genome |
| T60 | 859-866 | PR:Q9ZRV4 | denotes | at MLH1 |
| T64 | 862-866 | CVCL_G669 | denotes | MLH1 |
| T70 | 882-887 | 10090 | denotes | mouse |
| T71 | 882-887 | D051379 | denotes | mouse |
| T72 | 888-898 | SO:0000855 | denotes | orthologue |
| T73 | 908-911 | CVCL_D569 | denotes | CAG |
| T74 | 945-948 | PR:P51111 | denotes | Htt |
| T75 | 945-948 | PR:000015189 | denotes | Htt |
| T76 | 945-948 | PR:Q76P24 | denotes | Htt |
| T77 | 945-948 | PR:P31645 | denotes | Htt |
| T78 | 945-948 | PR:P42859 | denotes | Htt |
| T79 | 945-948 | PR:Q60857 | denotes | Htt |
| T80 | 945-948 | PR:P42858 | denotes | Htt |
| T81 | 945-948 | PR:000008840 | denotes | Htt |
| T82 | 958-963 | 10090 | denotes | mouse |
| T83 | 958-963 | D051379 | denotes | mouse |
| T84 | 1044-1062 | SO:0001536 | denotes | functional variant |
| T89 | 1162-1168 | SO:0001023 | denotes | allele |
| T90 | 1170-1181 | SO:0000991 | denotes | Genomic DNA |
| T92 | 1178-1181 | CHEBI:16991 | denotes | DNA |
| T94 | 1178-1181 | D004247 | denotes | DNA |
| T91 | 1178-1181 | GO:0005574 | denotes | DNA |
| T95 | 1219-1228 | SO:0001024 | denotes | haplotype |
| T97 | 1303-1307 | PR:Q9ZRV4 | denotes | MLH1 |
| T98 | 1303-1307 | PR:P38920 | denotes | MLH1 |
| T99 | 1303-1307 | PR:Q54KD8 | denotes | MLH1 |
| T101 | 1303-1307 | PR:Q9JK91 | denotes | MLH1 |
| T102 | 1303-1307 | PR:P97679 | denotes | MLH1 |
| T103 | 1303-1307 | PR:Q9P7W6 | denotes | MLH1 |
| T104 | 1303-1307 | PR:000010442 | denotes | MLH1 |
| T105 | 1303-1307 | PR:P40692 | denotes | MLH1 |
| T100 | 1303-1307 | CVCL_G669 | denotes | MLH1 |
| T106 | 1341-1348 | PR:Q91WK0 | denotes | LRRFIP2 |
| T107 | 1341-1348 | PR:Q9Y608 | denotes | LRRFIP2 |
| T108 | 1341-1348 | PR:Q4V7E8 | denotes | LRRFIP2 |
| T109 | 1341-1348 | PR:000009943 | denotes | LRRFIP2 |
| T111 | 1367-1377 | 6033 | denotes | isoleucine |
| T112 | 1367-1377 | SO:0001438 | denotes | isoleucine |
| T110 | 1367-1377 | CHEBI:24898 | denotes | isoleucine |
| T113 | 1367-1377 | CHEBI:17191 | denotes | isoleucine |
| T114 | 1367-1377 | D007532 | denotes | isoleucine |
| T115 | 1367-1377 | D007532 | denotes | isoleucine |
| T121 | 1378-1384 | 11115 | denotes | valine |
| T120 | 1378-1384 | SO:0001436 | denotes | valine |
| T116 | 1378-1384 | CHEBI:16414 | denotes | valine |
| T117 | 1378-1384 | D014633 | denotes | valine |
| T118 | 1378-1384 | D014633 | denotes | valine |
| T119 | 1378-1384 | CHEBI:27266 | denotes | valine |
| T123 | 1385-1401 | SO:0001583 | denotes | missense variant |
| T125 | 1405-1409 | PR:Q9ZRV4 | denotes | MLH1 |
| T126 | 1405-1409 | PR:P38920 | denotes | MLH1 |
| T127 | 1405-1409 | PR:Q54KD8 | denotes | MLH1 |
| T129 | 1405-1409 | PR:Q9JK91 | denotes | MLH1 |
| T130 | 1405-1409 | PR:P97679 | denotes | MLH1 |
| T131 | 1405-1409 | PR:Q9P7W6 | denotes | MLH1 |
| T132 | 1405-1409 | PR:000010442 | denotes | MLH1 |
| T133 | 1405-1409 | PR:P40692 | denotes | MLH1 |
| T128 | 1405-1409 | CVCL_G669 | denotes | MLH1 |
| T134 | 1502-1512 | GO:0065007 | denotes | regulation |
| T135 | 1516-1520 | PR:Q9ZRV4 | denotes | MLH1 |
| T136 | 1516-1520 | PR:P38920 | denotes | MLH1 |
| T137 | 1516-1520 | PR:Q54KD8 | denotes | MLH1 |
| T139 | 1516-1520 | PR:Q9JK91 | denotes | MLH1 |
| T140 | 1516-1520 | PR:P97679 | denotes | MLH1 |
| T141 | 1516-1520 | PR:Q9P7W6 | denotes | MLH1 |
| T142 | 1516-1520 | PR:000010442 | denotes | MLH1 |
| T143 | 1516-1520 | PR:P40692 | denotes | MLH1 |
| T138 | 1516-1520 | CVCL_G669 | denotes | MLH1 |
| T144 | 1525-1532 | PR:Q91WK0 | denotes | LRRFIP2 |
| T145 | 1525-1532 | PR:Q9Y608 | denotes | LRRFIP2 |
| T146 | 1525-1532 | PR:Q4V7E8 | denotes | LRRFIP2 |
| T147 | 1525-1532 | PR:000009943 | denotes | LRRFIP2 |
| T148 | 1584-1594 | GO:0065007 | denotes | regulation |
| T149 | 1642-1647 | SO:0001685 | denotes | score |