A novel RNAseq–assisted method for MHC class I genotyping in a non-model species applied to a lethal vaccination-induced alloimmune disease

Demasius, Wiebke; Weikard, Rosemarie; Hadlich, Frieder; Buitkamp, Johannes; Kühn, Christa

doi:10.1186/s12864-016-2688-0

Cited by 6 publications

(4 citation statements)

References 48 publications

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“…Novel holistic analyses, including whole transcriptome sequencing, have established new perspectives that have revealed previously unknown functions and regulatory responses in target tissues 24 . Especially for non-model organisms with incompletely annotated genomes and with many genes of yet unknown functions, RNA sequencing has provided new insights, e.g., into the immune responses to vaccination and infection 25 . Immune response to non-self antigens is highly species-specific 24 .…”

Section: Introductionmentioning

confidence: 99%

Different milk diets have substantial effects on the jejunal mucosal immune system of pre-weaning calves, as demonstrated by whole transcriptome sequencing

Hammon

Frieten

Gerbert³

et al. 2018

Sci Rep

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There is increasing evidence that nutrition during early mammalian life has a strong influence on health and performance in later life. However, there are conflicting data concerning the appropriate milk diet. This discrepancy particularly applies to ruminants, a group of mammals that switch from monogastric status to rumination during weaning. Little is known regarding how the whole genome expression pattern in the juvenile ruminant gut is affected by alternative milk diets. Thus, we performed a next-generation-sequencing-based holistic whole transcriptome analysis of the jejunum in male pre-weaned German Holstein calves fed diets with restricted or unlimited access to milk during the first 8 weeks of life. Both groups were provided hay and concentrate ad libitum. The analysis of jejunal mucosa samples collected 80 days after birth and four weeks after the end of the feeding regimes revealed 275 differentially expressed loci. While the differentially expressed loci comprised 67 genes encoding proteins relevant to metabolism or metabolic adaptation, the most distinct difference between the two groups was the consistently lower activation of the immune system in calves that experienced restricted milk access compared to calves fed milk ad libitum. In conclusion, different early life milk diets had significant prolonged effects on the intestinal immune system.

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Section: Introductionmentioning

confidence: 99%

Different milk diets have substantial effects on the jejunal mucosal immune system of pre-weaning calves, as demonstrated by whole transcriptome sequencing

Hammon

Frieten

Gerbert³

et al. 2018

Sci Rep

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“…This reflects the high genetic plasticity of MHC genes, which leads to population-specific allele sets. A similar method, RAMHCIT, has been used to determine MHC alleles from RNA-Seq data in cattle [34]. A prerequisite for the use of RAMHCIT is the availability of a larger number of known alleles (as in the case of bovine MHC), since more divergent alleles cannot be identified, resulting in largely incomplete genotyping.…”

Section: Discussionmentioning

confidence: 99%

Uncovering novel MHC alleles from RNA-Seq data: expanding the spectrum of MHC class I alleles in sheep

Buitkamp

2023

BMC Genom Data

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Background Major histocompatibility complex (MHC) class I glycoproteins present selected peptides or antigens to CD8 + T cells that control the cytotoxic immune response. The MHC class I genes are among the most polymorphic loci in the vertebrate genome, with more than twenty thousand alleles known in humans. In sheep, only a very small number of alleles have been described to date, making the development of genotyping systems or functional studies difficult. A cost-effective way to identify new alleles could be to use already available RNA-Seq data from sheep. Current strategies for aligning RNA-Seq reads against annotated genome sequences or transcriptomes fail to detect the majority of class I alleles. Here, I combine the alignment of RNA-Seq reads against a specific reference database with de novo assembly to identify alleles. The method allows the comprehensive discovery of novel MHC class I alleles from RNA-Seq data (DinoMfRS). Results Using DinoMfRS, virtually all expressed MHC class I alleles could be determined. From 18 animals 75 MHC class I alleles were identified, of which 69 were novel. In addition, it was shown that DinoMfRS can be used to improve the annotation of MHC genes in the sheep genome sequence. Conclusions DinoMfRS allows for the first time the annotation of unknown, more divergent MHC alleles from RNA-Seq data. Successful application to RNA-Seq data from 16 animals has approximately doubled the number of known alleles in sheep. By using existing data, alleles can now be determined very inexpensively for populations that have not been well studied. In addition, MHC expression studies or evolutionary studies, for example, can be greatly improved in this way, and the method should be applicable to a broader spectrum of other multigene families or highly polymorphic genes.

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“…This hypothesis is still controversial since MHC I alloantibodies would be expected to bind all nucleated cells, not only to blood-derived and hematopoietic progenitor cells (12, 16). Also transcriptome analyses provided evidence that MHC I can be excluded as single causal agent for BNP-associated alloantibodies (21). As other authors claimed the possibility of a genetic predisposition of BNP dams for production of BNP inducing alloantibodies (22–24), our studies focused on investigating a general difference in immune responses between PregSure BVD vaccinated control cows and BNP donors.…”

Section: Introductionmentioning

confidence: 99%

A Functionally Different Immune Phenotype in Cattle Is Associated With Higher Mastitis Incidence

K¹,

Kleinwort²,

Hobmaier³

et al. 2018

Front. Immunol.

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A novel vaccine against bovine viral diarrhea (BVD) induced pathogenic antibody production in 5–10% of BVD-vaccinated cows. Transfer of these antibodies via colostrum caused Bovine neonatal pancytopenia (BNP) in calves, with a lethality rate of 90%. The exact immunological mechanisms behind the onset of BNP are not fully understood to date. To gain further insight into these mechanisms, we analyzed the immune proteome from alloreactive antibody producers (BNP cows) and non-responders. After in vitro stimulation of peripheral blood derived lymphocytes (PBL), we detected distinctly deviant expression levels of several master regulators of immune responses in BNP cells, pointing to a changed immune phenotype with severe dysregulation of immune response in BNP cows. Interestingly, we also found this response pattern in 22% of non-BVD-vaccinated cows, indicating a genetic predisposition of this immune deviant (ID) phenotype in cattle. We additionally analyzed the functional correlation of the ID phenotype with 10 health parameters and 6 diseases in a retrospective study over 38 months. The significantly increased prevalence of mastitis among ID cows emphasizes the clinical relevance of this deviant immune response and its potential impact on the ability to fight infections.

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A novel RNAseq–assisted method for MHC class I genotyping in a non-model species applied to a lethal vaccination-induced alloimmune disease

Cited by 6 publications

References 48 publications

Different milk diets have substantial effects on the jejunal mucosal immune system of pre-weaning calves, as demonstrated by whole transcriptome sequencing

Different milk diets have substantial effects on the jejunal mucosal immune system of pre-weaning calves, as demonstrated by whole transcriptome sequencing

Uncovering novel MHC alleles from RNA-Seq data: expanding the spectrum of MHC class I alleles in sheep

A Functionally Different Immune Phenotype in Cattle Is Associated With Higher Mastitis Incidence

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