| 1. |
- Abdelmagid, N., et al.
(author)
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The Calcitonin Receptor Gene Is a Candidate for Regulation of Susceptibility to Herpes simplex Type 1 Neuronal Infection Leading to Encephalitis in Rat
- 2012
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In: Plos Pathogens. - : Public Library of Science (PLoS). - 1553-7374. ; 8:6
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Journal article (peer-reviewed)abstract
- Herpes simplex encephalitis (HSE) is a fatal infection of the central nervous system (CNS) predominantly caused by Herpes simplex virus type 1. Factors regulating the susceptibility to HSE are still largely unknown. To identify host gene(s) regulating HSE susceptibility we performed a genome-wide linkage scan in an intercross between the susceptible DA and the resistant PVG rat. We found one major quantitative trait locus (QTL), Hse1, on rat chromosome 4 (confidence interval 24.3-31 Mb; LOD score 29.5) governing disease susceptibility. Fine mapping of Hse1 using recombinants, haplotype mapping and sequencing, as well as expression analysis of all genes in the interval identified the calcitonin receptor gene (Calcr) as the main candidate, which also is supported by functional studies. Thus, using unbiased genetic approach variability in Calcr was identified as potentially critical for infection and viral spread to the CNS and subsequent HSE development.
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| 2. |
- Ayukekbong, James, et al.
(author)
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Monitoring of seasonality of norovirus and other enteric viruses in Cameroon by real-time PCR: an exploratory study
- 2014
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In: Epidemiology and Infection. - : Cambridge University Press (CUP). - 0950-2688 .- 1469-4409. ; 142:7, s. 1393-1402
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Journal article (peer-reviewed)abstract
- We studied the seasonal fluctuation of norovirus and other enteric viruses in Cameroon. Two hundred participants aged between 1 and 69 years were prospectively followed up. Each participant provided monthly faecal samples over a 12-month period. A total of 2484 samples were tested using multiplex real-time PCR assay for the detection of norovirus, rotavirus and enterovirus. The effect of weather variables and risk factors were analysed by Pearson correlation and bivariate analysis. Overall, enterovirus was the most commonly detected virus (216% of specimens), followed by norovirus (39%) and rotavirus (04%). Norovirus and enterovirus were detected throughout the year with a peak of norovirus detection at the beginning of the rainy season and a significant alternation of circulation of norovirus genogroups from one month to the next. Age <5 years and consumption of tap water were risk factors for norovirus infection. Better understanding of factors influencing transmission and seasonality may provide insights into the relationship between physical environment and risk of infection for these viruses.
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| 3. |
- Ayukekbong, James, et al.
(author)
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Pattern of Circulation of Norovirus GII Strains during Natural Infection
- 2014
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In: Journal of Clinical Microbiology. - : American Society for Microbiology. - 0095-1137 .- 1098-660X. ; 52:12, s. 4253-4259
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Journal article (peer-reviewed)abstract
- Norovirus (NoV) is considered a major cause of nonbacterial gastroenteritis among people of all ages worldwide, but the natural course of infection is incompletely known. In this study, the pattern of circulation of NoVs was studied among 146 children and 137 adults in a small community in southwestern Cameroon. The participants provided monthly fecal samples during a year. NoV RNA was detected in at least one sample from 82 (29%) of the participants. The partial VP1 region could be sequenced in 36 NoV GII-positive samples. Three different genotypes were identified (GII.1, GII.4, and GII.17), with each genotype circulating within 2 to 3 months and reappearing after a relapse period of 2 to 3 months. Most infections occurred once, and 2 episodes at most within a year were detected. No difference in the frequency of NoV infection between children and adults was recorded. The same genotype was detected for a maximum of 2 consecutive months in 3 children only, suggesting that a less than 30-day duration of viral shedding in natural infection was common. Reinfection within a year with the same genotype was not observed, consistent with short-term homotypic immune protection. The study revealed that NoV strains are circulating with a limited duration of viral shedding both in the individuals and the population as part of their natural infection. The results also provide evidence of cross-protective immunity of limited duration between genotypes of the same genogroup.
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| 4. |
- Ayukekbong, James, et al.
(author)
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Shift of Enterovirus species among children in Cameroon - Identification of a new enterovirus, EV-A119
- 2013
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In: Journal of Clinical Virology. - : Elsevier BV. - 1386-6532. ; 58:1, s. 227-232
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Journal article (peer-reviewed)abstract
- Background: Infections caused by human enteroviruses (EVs) are often asymptomatic or mild, although they may cause more severe illnesses as meningitis and acute flaccid paralysis. EVs have globally posed a threat to children, and outbreaks of aseptic meningitis and hand, foot and mouth disease are frequently reported. Objective: To identify EV strains circulating among healthy children in a small community in Limbe, Cameroon two years apart. Study design: Species and EV types were obtained by partial 5'UTR-VP4 and VP1 sequencing of RNA from stool samples collected in October 2009 and September 2011 from 150 children in Cameroon. Results: In all, 74 children (49%) were infected with 28 different types of EV. There were 29 (54%) infected children in 2009, and 45 (47%) in 2011. There was a significant difference between detected species of EV, with 15 (47%) children infected with EV-A in 2009, and 22 (71%) with EV-B in 2011 (p = 0.0001). In 2009, one child was infected by a divergent EV, which was most similar to EV-A90. Based on the complete VP1 sequence, it was shown to be a new EV designated EV-A119. Conclusion: The current study shows a high heterogeneity of circulating EV types among children in Limbe, Cameroon, and a previously not described shift in predominating EV species. (C) 2013 Elsevier B. V. All rights reserved.
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| 5. |
- Bergström, Tomas F.
(author)
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A novel mutation in TTC8 is associated with progressive retinal atrophy in the golden retriever
- 2014
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In: Canine Genetics and Epidemiology. - : Springer Science and Business Media LLC. - 2052-6687. ; 1
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Journal article (peer-reviewed)abstract
- Background: Generalized progressive retinal atrophy (PRA) is a group of inherited eye diseases characterised by progressive retinal degeneration that ultimately leads to blindness in dogs. To date, more than 20 different mutations causing canine-PRA have been described and several breeds including the Golden Retriever are affected by more than one form of PRA. Genetically distinct forms of PRA may have different clinical characteristics such as rate of progression and age of onset. However, in many instances the phenotype of different forms of PRA cannot be distinguished at the basic clinical level achieved during routine ophthalmoscopic examination. Mutations in two distinct genes have been reported to cause PRA in Golden Retrievers (prcd-PRA and GR_PRA1), but for approximately 39% of cases in this breed the causal mutation remains unknown. Results: A genome-wide association study of 10 PRA cases and 16 controls identified an association on chromosome 8 not previously associated with PRA (praw = 1.30×10-6 and corrected with 100,000 permutations, pgenome = 0.148). Using haplotype analysis we defined a 737 kb critical region containing 6 genes. Two of the genes (TTC8 and SPATA7) have been associated with Retinitis Pigmentosa (RP) in humans. Using targeted next generation sequencing a single nucleotide deletion was identified in exon 8 of the TTC8 gene of affected Golden Retrievers. The frame shift mutation was predicted to cause a premature termination codon. In a larger cohort, this mutation, TTC8c.669delA, segregates correctly in 22 out of 29 cases tested (75.9%). Of the PRA controls none are homozygous for the mutation, only 3.5% carry the mutation and 96.5% are homozygous wildtype. Conclusions: Our results show that PRA is genetically heterogeneous in one of the world's numerically largest breeds, the Golden Retriever, and is caused by multiple, distinct mutations. Here we discuss the mutation that causes a form of PRA, that we have termed PRA2, that accounts for approximately 30% of PRA cases in the breed. The genetic explanation for approximately 9% of cases remains to be identified. PRA2 is a naturally occurring animal model for Retinitis Pigmentosa, and potentially Bardet-Biedl Syndrome.
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| 6. |
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| 7. |
- Bergström, Tomas F.
(author)
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Assessment of a Novel Pigmentary Chorioretinopathy in the Chinese Crested Dog
- 2014
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In: JSM Ophthalmology. - 2333-6447. ; 2
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Journal article (peer-reviewed)abstract
- One hundred and twenty seven privately owned Chinese Crested Dogs (CCDs) were screened for Presumed Inherited Eye Disease (PIED). Thirty five cases of a recently discovered presumed inherited pigmentary chorioretinopathy were diagnosed and used for preliminary characterization of the disease using clinical and laboratory methods. Electroretinography (ERG) in ten affected and in nine normal CCDs was performed and morphology was obtained in one normal and in three affected 6-8 year-old dogs. A bilateral and mainly symmetrical retinal dystrophy with circumscribed pigmented lesions was observed, the earliest changes observed in 3-year-old dogs. The lesions showed a lighter center (pimple-like) and areas between lesions were often grayish and hypo reflective. Changes were mainly prevalent in the peripheral fundus initially. In more advanced cases the circumscribed pigmented changes were also observed centrally. In some cases there was diffuse hyper reflectivity in the area of the pigmented changes and slight vascular attenuation, indicating more generalized retinal degeneration. ERGs were not diagnostic in the early disease stage. Morphology showed changes at the level of the Retinal Pigment Epithelium (RPE), with focal areas of increased layering of RPE cells and detachment of RPE cells with subretinal migration. There were also areas of severe RPE and photoreceptor degeneration or atrophy with outer nuclear layer remnants in direct contact with the choroidal tissue. The circumscribed pigmented lesions observed ophthalmoscopically corresponded to these areas of geographic atrophy. The disease appears to be slowly progressive and in some cases, but not all, the disorder results in visual impairment or blindness.
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| 8. |
- Bergström, Tomas F.
(author)
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Assessment of Hereditary Retinal Degeneration in the English Springer Spaniel Dog and Disease Relationship to an RPGRIP1 Mutation
- 2012
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In: Stem Cells International. - : Hindawi Limited. - 1687-966X .- 1687-9678.
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Journal article (peer-reviewed)abstract
- Intensive breeding and selection on desired traits have produced high rates of inherited diseases in dogs. Hereditary retinal degeneration, often called progressive retinal atrophy (PRA), is prevalent in dogs with disease entities comparable to human retinitis pigmentosa (RP) and Leber's congenital amaurosis (LCA). Recent molecular studies in the English Springer Spaniel (ESS) dog have shown that PRA cases are often homozygous for a mutation in the RPGRIP1 gene, the defect also causing human RP, LCA, and cone rod dystrophies. The present study characterizes the disease in a group of affected ESS in USA, using clinical, functional, and morphological studies. An objective evaluation of retinal function using electroretinography (ERG) is further performed in a masked fashion in a group of American ESS dogs, with the examiner masked to the genetic status of the dogs. Only 4 of 6 homozygous animals showed clinical signs of disease, emphasizing the need and importance for more precise studies on the clinical expression of molecular defects before utilizing animal models for translational research, such as when using stem cells for therapeutic intervention.
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| 9. |
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| 10. |
- Bergström, Tomas F., et al.
(author)
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First genome-wide CNV mapping in FELIS CATUS using next generation sequencing data
- 2018
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In: BMC Genomics. - : Springer Science and Business Media LLC. - 1471-2164. ; 19
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Journal article (peer-reviewed)abstract
- BackgroundCopy Number Variations (CNVs) have becoming very significant variants, representing a major source of genomic variation. CNVs involvement in phenotypic expression and different diseases has been widely demonstrated in humans as well as in many domestic animals. However, genome wide investigation on these structural variations is still missing in Felis catus. The present work is the first CNV mapping from a large data set of Next Generation Sequencing (NGS) data in the domestic cat, performed within the 99 Lives Consortium.ResultsReads have been mapped on the reference assembly_6.2 by Maverix Biomics. CNV detection with cn.MOPS and CNVnator detected 592 CNVs. These CNVs were used to obtain 154 CNV Regions (CNVRs) with BedTools, including 62 singletons. CNVRs covered 0.26% of the total cat genome with 129 losses, 19 gains and 6 complexes. Cluster Analysis and Principal Component Analysis of the detected CNVRs showed that breeds tend to cluster together as well as cats sharing the same geographical origins. The 46 genes identified within the CNVRs were annotated.ConclusionThis study has improved the genomic characterization of 14 cat breeds and has provided CNVs information that can be used for studies of traits in cats. It can be considered a sound starting point for genomic CNVs identification in this species.
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