Denise Brocklebank's research while affiliated with University of Oxford and other places

Publications (14)

Article
Full-text available
The rate of decay of antibody concentration following serogroup C meningococcal (MenC) polysaccharide-protein conjugate vaccination varies between individuals. This depends partly on vaccination age but may be influenced by human genetics. We studied 721 single nucleotide polymorphisms (SNPs) across 131 candidate genes in a first cohort of 905 Cauc...
Article
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Correction to: European Journal of Human Genetics (2010) 18, 1013–1019; doi: 10.1038/ejhg.2010.69; published online 5 May 2010 Since the publication of the above paper, the authors noticed that one name is missing from the list of Autism MOLGEN members in the Appendix: Jeremy Parr Department of Psychiatry, University of Oxford, Oxford, UK The a...
Article
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Over the past decade, research on the genetic variants underlying susceptibility to autism and autism spectrum disorders (ASDs) has focused on linkage and candidate gene studies. This research has implicated various chromosomal loci and genes. Candidate gene studies have proven to be particularly intractable, with many studies failing to replicate...
Article
The ratio of female to male (F:M) multiple sclerosis (MS) cases varies geographically, generally being greater in areas of high prevalence. In many regions, including Canada, rising MS incidence in women has been implied by the marked increase in F:M ratio. We examined the F:M ratio over time in MS patients in the Canadian Collaborative Study born...
Article
The instability of the CAG repeat size of the HD gene when transmitted intergenerationally has critical implications for genetic counseling practices. In particular, CAG repeats between 27 and 35 have been the subject of debate based on small samples. To address this issue, we analyzed allelic instability in the Venezuelan HD kindreds, the largest...
Article
Synesthesia, a neurological condition affecting between 0.05%-1% of the population, is characterized by anomalous sensory perception and associated alterations in cognitive function due to interference from synesthetic percepts. A stimulus in one sensory modality triggers an automatic, consistent response in either another modality or a different a...
Article
The age of onset of Huntington's disease (HD) is inversely correlated with the CAG length in the HD gene. The CAG repeat length accounts for 70% of the variability in HD age of onset. However, 90% of individuals worldwide with expanded alleles possess between 40 and 50 CAG repeat lengths in their HD gene. For these people, the size of their repeat...
Article
Full-text available
The laboratory rat is one of the most extensively studied model organisms. Inbred laboratory rat strains originated from limited Rattus norvegicus founder populations, and the inherited genetic variation provides an excellent resource for the correlation of genotype to phenotype. Here, we report a survey of genetic variation based on almost 3 milli...
Article
Age of onset for Huntington's disease (HD) varies inversely with the length of the disease-causing CAG repeat expansion in the HD gene. A simple exponential regression model yielded adjusted R-squared values of 0.728 in a large set of Venezuelan kindreds and 0.642 in a North American, European, and Australian sample (the HD MAPS cohort). We present...
Article
Full-text available
The major determinant of age of onset in Huntington's disease is the length of the causative triplet CAG repeat. Significant variance remains, however, in residual age of onset even after repeat length is factored out. Many genetic polymorphisms have previously shown evidence of association with age of onset of Huntington's disease in several diffe...
Article
Full-text available
Huntington's disease (HD) is an autosomal dominant neurodegenerative disease caused by a triplet (CAG) expansion mutation. The length of the triplet repeat is the most important factor in determining age of onset of HD, although substantial variability remains after controlling for repeat length. The Venezuelan HD kindreds encompass 18,149 individu...

Citations

... Wu et al [35] 2013 HepB HLA-DPB1 HLA-DBP1 is significantly correlated with response to booster HepB vaccination in adolescent who had received postnatal active HepB vaccination. Moore et al [36] 2012 MenC CD44jTLR3 ...
... A wide array of molecular genetic studies, including linkage studies, CMA, WES, and genome-wide association studies (GWAS), have been applied to ASD to better understand its genetic basis. Although findings from linkage studies in subsets of families with affected siblings have led to the identification of possible susceptibility loci on multiple chromosomes (Badner and Gershon, 2002;Cantor et al., 2005;Holt et al., 2010), most of the identified regions have failed to reach suggestive linkage in larger sets of families, thus pointing to heterogeneity in ASD (for review, see Freitag, 2007). On the other hand, findings from CMA and other molecular tests have enabled the identification of several cytogenetically visible chromosomal abnormalities and de novo copy number variations (CNVs) in ASD, with an estimated rate of 3-6% (Konstantareas and Homatidis, 1999;Reddy, 2005) and 5-10% (Marshall et al., 2008;Pinto et al., 2010;Sebat et al., 2007) respectively. ...
... Elsewhere it was reported that SNPs or de novo mutations of the MKL1/MRTFA and MKL2/MRTFB genes might be involved in schizophrenia or autism spectrum disorder (ASD) [78][79][80]. For example, the combination of two largescale schizophrenia cohort studies highlighted seven SNPs on chromosome 22q13.1, ...
... Women are affected by multiple sclerosis (MS) more often than men and the sex difference in prevalence rates further increased during the last decades. [1][2][3][4] The reasons for the higher MS prevalence in women are uncertain, but genetic and hormonal factors have been implicated. 5 Pregnancies have a known impact on the MS disease course as relapse rates decrease substantially during pregnancy. ...
... For example, in grapheme-color synesthesia the experience of the letter A may automatically induce an experience of the color red. These inducer-concurrent pairs are idiosyncratic (i.e., they differ from one synesthete to another), highly specific (but may or may not be perceptual in nature), automatic (i.e., they cannot be turned on or off at will), consistent over time (and tend to be present in early childhood), and are thought to have a genetic component (Asher et al., 2009). ...
... Reports about whether people with an HTT gene that contains 27-35 CAG repeats are at risk for developing HD are controversial. Although CAG repeats in the 27-35 range are highly stable (49), some patients had the repeats extend into the HD onset range (>36), and some displayed HD symptoms even though their CAG repeats remained unchanged (46,47). This suggests that a portion of individuals with 27-35 intermediate CAG repeats can develop HD with or without the repeats expanding to 36. ...
... The most recent genetic modifier GWAS in HD (GeM-HD GWAS) 7 revealed 21 independent signals at 14 loci. We observed that one of the significant loci on chromosome 5 (5BM1) contained TCERG1, the only putative genetic modifier of HD onset in the GWAS to have been previously reported 9,10 . The 5BM1 locus (146 Mbp; hg19) has one significant single nucleotide variant (SNV), rs79727797 (p = 3.8 × 10 −10 ), with each minor allele conferring 2.3 years later onset of HD than expected from the subjects' CAG repeat length. ...
... However, the relationship between the AAO and modified genes is complex. The CAG repeat length of the expanded ATXN3 is the major AAO factor of SCA3/MJD, but other polyQ-related genes (CACNA1A, TBP, KCN3, RAI1, HTT, ATN 1, ATXN1, 2, and 7) and gene interactions also have modifying effects on the AAO (Andresen et al., 2007;Tezenas Du Montcel et al., 2014;Chen et al., 2016a). Other polyQ diseases, such as SCA1 (Wang et al., 2019), SCA2 (Hayes et al., 2000;Li et al., 2021), HD (Hmida-Ben Brahim et al., 2014), also have similar relationships. ...
... HD is caused by expansion of a CAG repeat region in exon 1 of the huntingtin (HTT) gene located on chromosome 4 beyond a pathogenic threshold of at least 37 CAGs (Figure 1A), with inheritance of 40 or more CAGs in this stretch associated with 100% disease penetrance (Ross and Tabrizi, 2011;Bates et al., 2015;Saudou and Humbert, 2016). HD exhibits genetic anticipation due to increased instability of expanded CAG repeats, and there exists a strong inverse relationship between CAG repeat length and age of symptom onset, with inheritance of >60 CAG repeats associated with highly-aggressive, juvenile-onset HD (Duyao et al., 1993;Wexler, 2004). Treatments currently available to HD patients can temporarily relieve motor or psychiatric symptoms, but effective disease-modifying therapies have yet to be developed. ...
... In an attempt to account for the extensive individual variation in addiction-related behaviors in humans, we employed the HR/LR model in outbred HS rats to assess how noveltyinduced locomotor behavior predicted OUD vulnerability in male and female rats. Heterogeneous stock (HS) rats were used for these studies as they exhibit considerably more behavioral and genetic variation than commonly used laboratory inbred lines (Hansen and Spuhler 1984, Consortium et al. 2008, Johannesson et al. 2009, Solberg Woods and Palmer 2019), resulting in diversity more akin to the human population. HS rats have been used to model such variation in several disorders, including SUD-related behaviors (Wang et al. 2018;Hughson et al. 2019;Kallupi et al. 2020;Deal et al. 2021;King et al. 2021). ...