https://nova.newcastle.edu.au/vital/access/ /manager/Index en-au 5 https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:46821 CRKL. A total of 45 of the 62 variants were associated with increased risk for CTDs (odds ratio [OR) ranges: 1.64–4.75). Associations of four variants were replicated in a meta-analysis of three genome-wide association studies of CTDs in affected individuals without 22q11.2DS. One of the replicated variants, rs178252, is located in an open chromatin region and resides in the double-elite enhancer, GH22J020947, that is predicted to regulate CRKL (CRK-like proto-oncogene, cytoplasmic adaptor) expression. Approximately 23% of patients with nested LCR22C-D deletions have CTDs, and inactivation of Crkl in mice causes CTDs, thus implicating this gene as a modifier. Rs178252 and rs6004160 are expression quantitative trait loci (eQTLs) of CRKL. Furthermore, set-based tests identified an enhancer that is predicted to target CRKL and is significantly associated with CTD risk (GH22J020946, sequence kernal association test (SKAT) p = 7.21 × 10−5) in the 22q11.2DS cohort. These findings suggest that variance in CTD penetrance in the 22q11.2DS population can be explained in part by variants affecting CRKL expression.]]> Wed 13 Mar 2024 15:07:07 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:12255 Wed 11 Apr 2018 10:02:00 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:9528 Sat 24 Mar 2018 08:35:32 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:12493 Sat 24 Mar 2018 08:17:11 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:10415 Sat 24 Mar 2018 08:12:38 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:18309 Sat 24 Mar 2018 08:04:40 AEDT ]]>