/manager/Index ${session.getAttribute("locale")} 5 Prevalence of PALB2 mutations in Australian familial breast cancer cases and controls /manager/Repository/uon:27356  G variant (rs152451) was significantly enriched in cases and may represent a low-penetrance polymorphism (p = 0.002; OR 1.24 (95 % CI 1.09–1.47). Conclusions: Our findings support truncating variants in PALB2 as high-penetrance breast cancer susceptibility alleles, and suggest that a common missense variant may also lead to a low level of increased breast cancer risk.]]> Wed 11 Apr 2018 17:01:50 AEST ]]> Bioinformatics-based identification of expanded repeats:a non-reference intronic pentamer expansion in RFC1 causes CANVAS /manager/Repository/uon:36658 exp] in the gene encoding Replication Factor C1 (RFC1). This motif, not reported in the reference sequence, localized to an Alu element and replaced the reference (AAAAG)11 short tandem repeat. Genetic analyses confirmed the pathogenic expansion in 18 of 22 CANVAS-affected families and identified a core ancestral haplotype, estimated to have arisen in Europe more than twenty-five thousand years ago. WGS of the four RFC1-negative CANVAS-affected families identified plausible variants in three, with genomic re-diagnosis of SCA3, spastic ataxia of the Charlevoix-Saguenay type, and SCA45. This study identified the genetic basis of CANVAS and demonstrated that these improved bioinformatics tools increase the diagnostic utility of WGS to determine the genetic basis of a heterogeneous group of clinically overlapping neurogenetic disorders.]]> Mon 22 Jun 2020 15:22:42 AEST ]]>