A novel locus on mouse chromosome 7 that influences survival after infection with tick-borne encephalitis virus

Palus, Martin; Sohrabi, Yahya; Broman, Karl W.; Strnad, Hynek; Šíma, Matyáš; Růžek, Daniel; Volkova, Valeriya; Slapničková, Martina; Vojtíšková, Jarmila; Mrázková, Lucie; Salát, Jiřı́; Lipoldová, Marie

doi:10.1186/s12868-018-0438-8

Cited by 15 publications

(6 citation statements)

References 51 publications

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“…Linkage analysis identified a novel suggestive locus on chromosome 7. This locus contained nine candidate genes ( Cd33, Klk1b22, Siglece, Klk1b16, Fut2, Grwd1, Abcc6, Otog, and Mkrn3 ), which may be a focus of future studies not only in mice, but also in humans [30].…”

Section: Introductionmentioning

confidence: 99%

Exome-wide search and functional annotation of genes associated in patients with severe tick-borne encephalitis in a Russian population

et al. 2019

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Background Tick-borne encephalitis (TBE) is a viral infectious disease caused by tick-borne encephalitis virus (TBEV). TBEV infection is responsible for a variety of clinical manifestations ranging from mild fever to severe neurological illness. Genetic factors involved in the host response to TBEV that may potentially play a role in the severity of the disease are still poorly understood. In this study, using whole-exome sequencing, we aimed to identify genetic variants and genes associated with severe forms of TBE as well as biological pathways through which the identified variants may influence the severity of the disease. Results Whole-exome sequencing data analysis was performed on 22 Russian patients with severe forms of TBE and 17 Russian individuals from the control group. We identified 2407 candidate genes harboring rare, potentially pathogenic variants in exomes of patients with TBE and not containing any rare, potentially pathogenic variants in exomes of individuals from the control group. According to DAVID tool, this set of 2407 genes was enriched with genes involved in extracellular matrix proteoglycans pathway and genes encoding proteins located at the cell periphery. A total of 154 genes/proteins from these functional groups have been shown to be involved in protein-protein interactions (PPIs) with the known candidate genes/proteins extracted from TBEVHostDB database. By ranking these genes according to the number of rare harmful minor alleles, we identified two genes ( MSR1 and LMO7), harboring five minor alleles, and three genes ( FLNA, PALLD, PKD1 ) harboring four minor alleles. When considering genes harboring genetic variants associated with severe forms of TBE at the suggestive P -value < 0.01, 46 genes containing harmful variants were identified. Out of these 46 genes, eight ( MAP4, WDFY4, ACTRT2, KLHL25, MAP2K3, MBD1, OR10J1, and OR2T34) were additionally found among genes containing rare pathogenic variants identified in patients with TBE; and five genes ( WDFY4 , ALK, MAP4, BNIPL, EPPK1 ) were found to encode proteins that are involved in PPIs with proteins encoded by genes from TBEVHostDB. Three genes out of five ( MAP4, EPPK1, ALK ) were found to encode proteins located at cell periphery. Conclusions Whole-exome sequencing followed by systems biology approach enabled to identify eight candidate genes ( MAP4, WDFY4, ACTRT2, KLHL25, MAP2K3, MBD1, OR10J1, and OR2T34 ) that can potentially determine predisposition to severe forms of TBE. Analyses of the genetic risk factors for severe forms of TBE revealed a significant enrichment with genes controlling extracellular matrix proteoglycans pathway as well...

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Section: Introductionmentioning

confidence: 99%

Exome-wide search and functional annotation of genes associated in patients with severe tick-borne encephalitis in a Russian population

et al. 2019

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“…Additionally, it has been described that all potential candidate genes are expressed, inter alia, in the brain, and it is well known that the TBEV directly infects the brain and causes encephalitis. However, further research on human samples is needed to evaluate the association between genes located on chromosome 7 and the susceptibility to TBEV infection [ 69 ].…”

Section: Resultsmentioning

confidence: 99%

Selected Biomarkers of Tick-Borne Encephalitis: A Review

Gudowska-Sawczuk

Mroczko

2021

IJMS

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Tick-borne encephalitis (TBE) is an acute disease caused by the tick-borne encephalitis virus. Due to the viral nature of the condition, there is no effective causal treatment for full-blown disease. Current and nonspecific TBE treatments only relieve symptoms. Unfortunately, the first phase of TBE is characterized by flu-like symptoms, making diagnosis difficult during this period. The second phase is referred to as the neurological phase as it involves structures in the central nervous system—most commonly the meninges and, in more severe cases, the brain and the spinal cord. Therefore, it is important that early markers of TBE that will guide clinical decision-making and the choice of treatment are established. In this review, we performed an extensive search of literature reports relevant to biomarkers associated with TBE using the MEDLINE/PubMed database. We observed that apart from routinely determined specific immunoglobulins, free light chains may also be useful in the evaluation of intrathecal synthesis in the central nervous system (CNS) during TBEV infection. Moreover, selected metalloproteinases, chemokines, or cytokines appear to play an important role in the pathogenesis of TBE as a consequence of inflammatory reactions and recruitment of white blood cells into the CNS. Furthermore, we reported promising findings on tau protein or Toll-like receptors. It was also observed that some people may be predisposed to TBE. Therefore, to understand the role of selected tick-borne encephalitis biomarkers, we categorized these factors and discussed their potential application in the diagnosis, prognosis, monitoring, or management of TBE.

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“…We have sequenced the genomes of strains C57BL/10 and O20 using next-generation sequencing (NGS) system HiSeq 2500 (Illumina) (12× coverage). Processing, alignment, sorting and indexing of NGS data, variants filtration, annotation, and effect prediction were performed as described elsewhere ( 30 ). In detail, NGS data were preprocessed using software Trimmomatic ( 31 ) and overlapping pair reads were joined by software Flash ( 32 ).…”

Section: Methodsmentioning

confidence: 99%

Genetic Influence on Frequencies of Myeloid-Derived Cell Subpopulations in Mouse

et al. 2022

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Differences in frequencies of blood cell subpopulations were reported to influence the course of infections, atopic and autoimmune diseases, and cancer. We have discovered a unique mouse strain B10.O20 containing extremely high frequency of myeloid-derived cells (MDC) in spleen. B10.O20 carries 3.6% of genes of the strain O20 on the C57BL/10 genetic background. It contains much higher frequency of CD11b+Gr1+ cells in spleen than both its parents. B10.O20 carries O20-derived segments on chromosomes 1, 15, 17, and 18. Their linkage with frequencies of blood cell subpopulations in spleen was tested in F2 hybrids between B10.O20 and C57BL/10. We found 3 novel loci controlling MDC frequencies: Mydc1, 2, and 3 on chromosomes 1, 15, and 17, respectively, and a locus controlling relative spleen weight (Rsw1) that co-localizes with Mydc3 and also influences proportion of white and red pulp in spleen. Mydc1 controls numbers of CD11b+Gr1+ cells. Interaction of Mydc2 and Mydc3 regulates frequency of CD11b+Gr1+ cells and neutrophils (Gr1+Siglec-F- cells from CD11b+ cells). Interestingly, Mydc3/Rsw1 is orthologous with human segment 6q21 that was shown previously to determine counts of white blood cells. Bioinformatics analysis of genomic sequence of the chromosomal segments bearing these loci revealed polymorphisms between O20 and C57BL/10 that change RNA stability and genes’ functions, and we examined expression of relevant genes. This identified potential candidate genes Smap1, Vps52, Tnxb, and Rab44. Definition of genetic control of MDC can help to personalize therapy of diseases influenced by these cells.

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A novel locus on mouse chromosome 7 that influences survival after infection with tick-borne encephalitis virus

Cited by 15 publications

References 51 publications

Exome-wide search and functional annotation of genes associated in patients with severe tick-borne encephalitis in a Russian population

Exome-wide search and functional annotation of genes associated in patients with severe tick-borne encephalitis in a Russian population

Selected Biomarkers of Tick-Borne Encephalitis: A Review

Genetic Influence on Frequencies of Myeloid-Derived Cell Subpopulations in Mouse

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