Characterisation of the genomic architecture of human chromosome 17q and evaluation of different methods for haplotype block definition

BACKGROUND: The selection of markers in association studies can be informed through the use of haplotype blocks. Recent reports have determined the genomic architecture of chromosomal segments through different haplotype block definitions based on linkage disequilibrium (LD) measures or haplotype diversity criteria. The relative applicability of distinct block definitions to association studies, however, remains unclear. We compared different block definitions in 6.1 Mb of chromosome 17q in 189 unrelated healthy individuals. Using 137 single nucleotide polymorphisms (SNPs), at a median spacing of 15.5 kb, we constructed haplotype block maps using published methods and additional methods we have developed. Haplotype tagging SNPs (htSNPs) were identified for each map. RESULTS: Blocks were found to be shorter and coverage of the region limited with methods based on LD measures, compared to the method based on haplotype diversity. Although the distribution of blocks was highly variable, the number of SNPs that needed to be typed in order to capture the maximum number of haplotypes was consistent. CONCLUSION: For the marker spacing used in this study, choice of block definition is not important when used as an initial screen of the region to identify htSNPs. However, choice of block definition has consequences for the downstream interpretation of association study results

Canine Genetics and Epidemiology is now Canine Medicine and Genetics

From Springer Nature via Jisc Publications RouterHistory: registration 2020-07-17, online 2020-07-27, pub-electronic 2020-07-27, collection 2020-12Publication status: Publishe

Analysis of normal and osteoarthritic canine cartilage mRNA expression by quantitative polymerase chain reaction

The molecular basis to mammalian osteoarthritis (OA) is unknown. We hypothesised that the expression of selected proteases, matrix molecules, and collagens believed to have a role in the pathogenesis of OA would be changed in naturally occurring canine OA cartilage when compared to normal articular cartilage. Quantitative (real-time) reverse transcriptase-polymerase chain reaction assays were designed measuring the expression of selected matrix molecules (collagens and small leucine-rich proteoglycans), key mediators of the proteolytic degradation of articular cartilage (metalloproteinases, cathepsins), and their inhibitors (tissue inhibitors of matrix metalloproteinases). All data were normalised using a geometric mean of three housekeeping genes, and the results subjected to power calculations and corrections for multiple hypothesis testing. We detected increases in the expression of BGN, COL1A2, COL2A1, COL3A1, COL5A1, CSPG2, CTSB, CTSD, LUM, MMP13, TIMP1, and TNC in naturally occurring canine OA. The expression of TIMP2 and TIMP4 was significantly reduced in canine OA cartilage. The patterns of gene expression change observed in naturally occurring canine OA were similar to those reported in naturally occurring human OA and experimental canine OA. We conclude that the expression profiles of matrix-associated molecules in end-stage mammalian OA may be comparable but that the precise aetiologies of OA affecting specific joints in different species are presently unknown

Canine candidate genes for dilated cardiomyopathy: annotation of and polymorphic markers for 14 genes

BackgroundDilated cardiomyopathy is a myocardial disease occurring in humans and domestic animals and is characterized by dilatation of the left ventricle, reduced systolic function and increased sphericity of the left ventricle. Dilated cardiomyopathy has been observed in several, mostly large and giant, dog breeds, such as the Dobermann and the Great Dane. A number of genes have been identified, which are associated with dilated cardiomyopathy in the human, mouse and hamster. These genes mainly encode structural proteins of the cardiac myocyte.ResultsWe present the annotation of, and marker development for, 14 of these genes of the dog genome, i.e. alpha-cardiac actin, caveolin 1, cysteine-rich protein 3, desmin, lamin A/C, LIM-domain binding factor 3, myosin heavy polypeptide 7, phospholamban, sarcoglycan delta, titin cap, alpha-tropomyosin, troponin I, troponin T and vinculin. A total of 33 Single Nucleotide Polymorphisms were identified for these canine genes and 11 polymorphic microsatellite repeats were developed.ConclusionThe presented polymorphisms provide a tool to investigate the role of the corresponding genes in canine Dilated Cardiomyopathy by linkage analysis or association studies

The Genetic Basis of Individual-Recognition Signals in the Mouse

SummaryThe major histocompatibility complex (MHC) is widely assumed to be a primary determinant of individual-recognition scents in many vertebrates [1–6], but there has been no functional test of this in animals with normal levels of genetic variation. Mice have evolved another polygenic and highly polymorphic set of proteins for scent communication, the major urinary proteins (MUPs) [7–12], which may provide a more reliable identity signature ([13, 14] and A.L. Sherborne, M.D.T., S. Paterson, F.J., W.E.R.O., P. Stockley, R.J.B., and J.L.H., unpublished data). We used female preference for males that countermark competitor male scents [15–17] to test the ability of wild-derived mice to recognize individual males differing in MHC or MUP type on a variable genetic background. Differences in MHC type were not used for individual recognition. Instead, recognition depended on a difference in MUP type, regardless of other genetic differences between individuals. Recognition also required scent contact, consistent with detection of involatile components through the vomeronasal system [6, 18]. Other differences in individual scent stimulated investigation but did not result in individual recognition. Contrary to untested assumptions of a vertebrate-wide mechanism based largely on MHC variation, mice use a species-specific [12] individual identity signature that can be recognized reliably despite the complex internal and external factors that influence scents [2]. Specific signals for genetic identity recognition in other species now need to be investigated

The prevalence of long COVID in people with diabetes mellitus–evidence from a UK cohort

Background: It was apparent from the early phase of the SARS-CoV-2 virus (COVID-19) pandemic that a multi-system syndrome can develop in the weeks following a COVID-19 infection, now referred to as Long COVID. Given that people living with diabetes are at increased risk of hospital admission/poor outcomes following COVID-19 infection we hypothesised that they may also be more susceptible to developing Long COVID. We describe here the prevalence of Long COVID in people living with diabetes when compared to matched controls in a Northwest UK population. Methods: This was a retrospective cohort study of people who had a recorded diagnosis of type 1 diabetes (T1D) or type 2 diabetes (T2D) who were alive on 1st January 2020 and who had a proven COVID-19 infection. We used electronic health record data from the Greater Manchester Care Record collected from 1st January 2020 to 16th September 2023, we determined the prevalence of Long COVID in people with T1D and T2D vs matched individuals without diabetes (non-DM). Findings: There were 3087 T1D individuals with 14,077 non-diabetes controls and 3087 T2D individuals with 14,077 non-diabetes controls and 29,700 T2D individuals vs 119,951 controls. For T1D, there was a lower proportion of Long COVID diagnosis and/or referral to a Long COVID service at 0.33% vs 0.48% for matched controls. The prevalence of Long COVID In T2D individuals was 0.53% vs 1:3 matched controls 0.54%. For T2D, there were differences by sex in the prevalence of Long COVID in comparison with 1:3 matched controls. For Long COVID between males with T2D and their matched controls, the prevalence was lower in matched controls at 0.46%.vs 0.54% (0.008). When considering the prevalence of LC between females with T2D and their matched controls, the prevalence was higher in matched controls at 0.61% vs 0.53% (0.007). The prevalence of Long COVID in males with T2D vs females was not different. T2D patients at older vs younger age were at reduced risk of developing Long COVID (OR 0.994 [95% CI) [0.989, 0.999]). For females there was a minor increase of risk (OR 1.179, 95% CI [1.002, 1.387]). Presence of a higher body mass index (BMI) was also associated an increased risk of developing Long COVID (OR 1.013, 95% CI [1.001, 1.026]). The estimated general population prevalence of Long COVID based on general practice coding (not self-reported) of this diagnosis was 0.5% of people with a prior acute COVID-19 diagnosis. Interpretation: Recorded Long COVID was more prevalent in men with T2D than in matched non-T2D controls with the opposite seen for T2D women, with recorded Long COVID rates being similar for T2D men and women. Younger age, female sex and higher BMI were all associated with a greater likelihood of developing Long COVID when taken as individual variables. There remains an imperative for continuing awareness of Long COVID as a differential diagnosis for multi-system symptomatic presentation in the context of a previous acute COVID-19 infection. Funding: The time of co-author RW was supported by the NIHR Applied Research Collaboration Greater Manchester ( NIHR200174) and the NIHR Manchester Biomedical Research Centre ( NIHR203308)

The UK DNA banking network: a “fair access” biobank

The UK DNA Banking Network (UDBN) is a secondary biobank: it aggregates and manages resources (samples and data) originated by others. The network comprises, on the one hand, investigator groups led by clinicians each with a distinct disease specialism and, on the other hand, a research infrastructure to manage samples and data. The infrastructure addresses the problem of providing secure quality-assured accrual, storage, replenishment and distribution capacities for samples and of facilitating access to DNA aliquots and data for new peer-reviewed studies in genetic epidemiology. ‘Fair access’ principles and practices have been pragmatically developed that, unlike open access policies in this area, are not cumbersome but, rather, are fit for the purpose of expediting new study designs and their implementation. UDBN has so far distributed >60,000 samples for major genotyping studies yielding >10 billion genotypes. It provides a working model that can inform progress in biobanking nationally, across Europe and internationally