| Id |
Subject |
Object |
Predicate |
Lexical cue |
| T1 |
0-90 |
DRI_Challenge |
denotes |
Parent-of-origin differences of mutant HTT CAG repeat instability in Huntington's disease. |
| T2 |
103-246 |
DRI_Challenge |
denotes |
Huntington's disease (HD) is a progressive autosomal dominant neurodegenerative disorder caused by a CAG repeat expansion in the HD gene (HTT). |
| T3 |
247-382 |
DRI_Challenge |
denotes |
The CAG domain of mutant HTT is unstable upon intergenerational transmission, however, little is known about the underlying mechanisms. |
| T4 |
392-544 |
DRI_Approach |
denotes |
From the HD archives of the Leiden University Medical Centre DNA samples from all parent-offspring pairs involving 36 CAG repeats or more were selected. |
| T5 |
545-759 |
DRI_Approach |
denotes |
To minimize procedural variability, CAG repeat lengths in both mutant and normal HTT were reassessed using the same standardized protocol, which resulted in the identification of 337 parent-offspring transmissions. |
| T6 |
760-945 |
DRI_Outcome |
denotes |
The effects of both parental (mutant and normal CAG repeat size, age and gender) and offspring (gender and season of conception) characteristics on CAG repeat instability were assessed. |
| T7 |
955-1140 |
DRI_Approach |
denotes |
Paternal transmissions were often associated with CAG repeat expansion, whereas maternal transmissions mainly resulted in CAG repeat contraction (mean change: +1.76 vs. -0.07, p<0.001). |
| T8 |
1141-1281 |
DRI_Outcome |
denotes |
Only in paternal transmissions larger mutant CAG repeat size was associated with a greater degree of CAG repeat expansion (β=0.73; p<0.001). |
| T9 |
1282-1451 |
DRI_Outcome |
denotes |
Conversely, only in maternal transmissions larger CAG repeat size of the normal allele was associated with a greater degree of CAG repeat contraction (β=-0.07; p=0.029). |
| T10 |
1452-1551 |
DRI_Background |
denotes |
Parental age, offspring gender and season of conception were not related to CAG repeat instability. |
| T11 |
1564-1806 |
DRI_Outcome |
denotes |
Our findings suggest a slight maternal contraction bias as opposed to a paternal expansion bias of the mutant HTT CAG repeat during intergenerational transmission, which only in the maternal line is associated with normal HTT CAG repeat size. |
