scholarly journals Splicing QTL analysis focusing on coding sequences reveals pathogenicity of disease susceptibility loci.

2022 ◽  
Author(s):  
Kensuke Yamaguchi ◽  
Kazuyoshi Ishigaki ◽  
Akari Suzuki ◽  
Yumi Tsuchida ◽  
Haruka Tsuchiya ◽  
...  
Keyword(s):  
Protein Structure ◽  
Disease Susceptibility ◽  
Susceptibility Loci ◽  
Rna Seq ◽  
Coding Sequences ◽  
Altered Protein ◽  
Long Read ◽  
Novel Approaches ◽  
Selection For

Splicing QTL (sQTL) are one of the major causal mechanisms in GWAS loci, but their role in disease pathogenesis is poorly understood. One reason is the huge complexity of alternative splicing events producing many unknown isoforms. Here, we proposed two novel approaches, namely integration and selection, for this complexity by focusing on protein-structure of isoforms. First, we integrated isoforms with the same coding sequence (CDS) and identified 369-601 integrated-isoform ratio QTLs (i2-rQTLs), which altered protein-structure, in six immune subsets. Second, we selected CDS incomplete isoforms annotated in GENCODE and identified 175-337 isoform-ratio QTL (i-rQTL). By comprehensive long-read capture RNA-seq among these incomplete isoforms, we revealed 29 full-length isoforms with novel CDSs associated with GWAS traits. Furthermore, we have shown that disease-causal sQTL genes can be identified by evaluating their trans-eQTL effects. Our approaches highlight the understudied role of protein-altering sQTLs and are broadly applicable to other tissues and diseases.

952 The Role of Genetic Crohn's Disease Susceptibility Loci in Small Bowel Transplant Outcome

2010 ◽  
Vol 138 (5) ◽  
pp. S-139
Author(s):  
Marcel Janse ◽  
Rinse K. Weersma ◽  
Gerard Dijkstra ◽  
Eleonora A. Festen ◽  
Debra L. Sudan ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Small Bowel ◽  
Crohn's Disease ◽  
Disease Susceptibility ◽  
Susceptibility Loci ◽  
Transplant Outcome ◽  
Small Bowel Transplant

Novel Approaches in the Treatment of Antipsychotic-Induced Hyperprolactinemia:The Role of Partial Agonists of D2 Dopaminergic Receptors

2010 ◽  
Vol 4 (3) ◽  
pp. 230-240 ◽  
Author(s):  
Domenico De Berardis ◽  
Tiziano Acciavatti ◽  
Daniela Campanella ◽  
Nicola Serroni ◽  
Luigi Olivieri ◽  
...  
Keyword(s):  
Dopaminergic Receptors ◽  
Partial Agonists ◽  
Novel Approaches

scholarly journals Analysis of HLA-G long-read genomic sequences in mother–offspring pairs with preeclampsia

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Ayako Nishizawa ◽  
Kazuki Kumada ◽  
Keiko Tateno ◽  
Maiko Wagata ◽  
Sakae Saito ◽  
...  
Keyword(s):  
Single Molecule ◽  
Gene Polymorphisms ◽  
Genomic Dna ◽  
Genomic Sequences ◽  
Genomic Sequencing ◽  
Public Database ◽  
Coding Sequences ◽  
Pacbio Rs Ii ◽  
Potential Association ◽  
Long Read

AbstractPreeclampsia is a pregnancy-induced disorder that is characterized by hypertension and is a leading cause of perinatal and maternal–fetal morbidity and mortality. HLA-G is thought to play important roles in maternal–fetal immune tolerance, and the associations between HLA-G gene polymorphisms and the onset of pregnancy-related diseases have been explored extensively. Because contiguous genomic sequencing is difficult, the association between the HLA-G genotype and preeclampsia onset is controversial. In this study, genomic sequences of the HLA-G region (5.2 kb) from 31 pairs of mother–offspring genomic DNA samples (18 pairs from normal pregnancies/births and 13 from preeclampsia births) were obtained by single-molecule real-time sequencing using the PacBio RS II platform. The HLA-G alleles identified in our cohort matched seven known HLA-G alleles, but we also identified two new HLA-G alleles at the fourth-field resolution and compared them with nucleotide sequences from a public database that consisted of coding sequences that cover the 3.1-kb HLA-G gene span. Intriguingly, a potential association between preeclampsia onset and the poly T stretch within the downstream region of the HLA-G*01:01:01:01 allele was found. Our study suggests that long-read sequencing of HLA-G will provide clues for characterizing HLA-G variants that are involved in the pathophysiology of preeclampsia.

scholarly journals Antimicrobials and Food-Related Stresses as Selective Factors for Antibiotic Resistance along the Farm to Fork Continuum

Antibiotics ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 671
Author(s):  
Federica Giacometti ◽  
Hesamaddin Shirzad-Aski ◽  
Susana Ferreira
Keyword(s):  
Antibiotic Resistance ◽  
Food Safety ◽  
Antimicrobial Resistance ◽  
Food Processing ◽  
Resistance Mechanisms ◽  
Human Environment ◽  
Real Risk ◽  
Cross Adaptation ◽  
Novel Approaches

Antimicrobial resistance (AMR) is a global problem and there has been growing concern associated with its widespread along the animal–human–environment interface. The farm-to-fork continuum was highlighted as a possible reservoir of AMR, and a hotspot for the emergence and spread of AMR. However, the extent of the role of non-antibiotic antimicrobials and other food-related stresses as selective factors is still in need of clarification. This review addresses the use of non-antibiotic stressors, such as antimicrobials, food-processing treatments, or even novel approaches to ensure food safety, as potential drivers for resistance to clinically relevant antibiotics. The co-selection and cross-adaptation events are covered, which may induce a decreased susceptibility of foodborne bacteria to antibiotics. Although the available studies address the complexity involved in these phenomena, further studies are needed to help better understand the real risk of using food-chain-related stressors, and possibly to allow the establishment of early warnings of potential resistance mechanisms.

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