https://nova.newcastle.edu.au/vital/access/manager/Index ${session.getAttribute("locale")} 5 https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:13674 Wed 24 Jun 2020 12:51:30 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:13672 Wed 11 Apr 2018 16:23:10 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:13671 Wed 11 Apr 2018 16:06:02 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:13673 Wed 11 Apr 2018 15:24:43 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:24220 A and −174 G>C) correlate with MS susceptibility, but with varying results. In the present study, we analyzed these polymorphisms, together with an additional polymorphism (−572 G>C) in 279 healthy controls and 509 patients with MS. We found no significant differences between MS patients and healthy controls for the different −597 or −174 IL6 promoter alleles or genotypes. There was a slight reduction in the percentage of individuals with MS who carried a C allele at position −572, although this was not significant after correction for multiple comparisons. Interestingly, however, the −572 C allele showed a significant correlation with the MS severity score, suggesting a possible role in disease progression.]]> Wed 11 Apr 2018 15:18:27 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:26643 Wed 11 Apr 2018 13:39:49 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:13696 Wed 11 Apr 2018 12:04:40 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:22235 −6). Network analysis of cases and controls sharing haplotypes on chromosome 19 further strengthened the association as there are more large networks of cases sharing haplotypes than controls. This linkage region includes a cluster of zinc finger genes of unknown function. Analysis of genome wide transcriptome data suggests that genes in this zinc finger cluster may be involved in very early developmental regulation of the CNS. Our study also indicates that BEAGLE fastIBD allowed identification of rare variants in large unrelated population with moderate computational intensity. Even with the development of whole-genome sequencing, IBD mapping still may be a promising way to narrow down the region of interest for sequencing priority.]]> Wed 11 Apr 2018 11:41:58 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:20566 Wed 11 Apr 2018 10:41:17 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:7518 Sat 24 Mar 2018 08:38:28 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:12845 T at 3p24.1 (odds ratio [OR], 1.17; p = 1.6 × 10⁻⁸) near EOMES, rs2150702^G in the second intron of MLANA on chromosome 9p24.1 (OR, 1.16; p = 3.3 × 10⁻⁸), and rs6718520^A in an intergenic region on chromosome 2p21, with THADA as the nearest flanking gene (OR, 1.17; p = 3.4 × 10⁻⁸). The 3 new loci do not have a strong cis effect on RNA expression in PBMCs. Ten other susceptibility loci had a suggestive p < 1 × 10⁻⁶, some of these loci have evidence of association in other inflammatory diseases (ie, IL12B, TAGAP, PLEK, and ZMIZ1). Interpretation: We have performed a meta-analysis of GWAS in MS that more than doubles the size of previous gene discovery efforts and highlights 3 novel MS susceptibility loci. These and additional loci with suggestive evidence of association are excellent candidates for further investigations to refine and validate their role in the genetic architecture of MS.]]> Sat 24 Mar 2018 08:17:22 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:20501 Sat 24 Mar 2018 07:59:03 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:18970 Sat 24 Mar 2018 07:58:53 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:25277 −11; odds ratio (OR) = 1.42, 95% confidence interval (CI) = 1.28–1.57). All four loci exhibited evidence for heterogeneity of effect across the stroke subtypes, with some and possibly all affecting risk for only one subtype. This suggests distinct genetic architectures for different stroke subtypes.]]> Sat 24 Mar 2018 07:38:17 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:29884 PIGN were identified in the siblings, with appropriate parental segregation: a novel STOP mutation (c.1966C>T: p.Glu656X) and a rare (minor allele frequency <0.001) donor splice site mutation (c.1674+1G>C) causing skipping of exon 18 and utilization of a cryptic acceptor site in exon 19. A further novel homozygous STOP mutation in PIGN (c.694A>T: p.Lys232X) was detected in one unrelated case. All three variants affected highly conserved bases. The two remaining cases were negative for PIGN mutations. Mutations in PIGN have been reported in cases with multiple congenital anomalies, including one case with syndromic CDH. Fryns syndrome can be caused by recessive mutations in PIGN. Whether PIGN affects other syndromic and non-syndromic forms of CDH warrants investigation.]]> Sat 24 Mar 2018 07:33:47 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:25354 Sat 24 Mar 2018 07:24:42 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:42186 n = 3,473) by performing identity-by-descent (IBD) mapping followed by exome sequencing of individuals identified as sharing risk haplotypes to search for rare risk variants in coding regions. We identified 45 rare haplotypes (>1 cM) that were significantly more common in cases than controls. By exome sequencing 105 haplotype carriers, we investigated these haplotypes for functional coding variants that could be tested for association in independent GWAS samples. We identified one rare missense variant in PCNT but did not find statistical support for an association with schizophrenia in a replication analysis. However, IBD mapping can prioritize both individual samples and genomic regions for follow-up analysis but genome rather than exome sequencing may be more effective at detecting risk variants on rare haplotypes.]]> Fri 26 Aug 2022 10:49:17 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:49494 Fri 19 May 2023 10:52:01 AEST ]]>