A possible mechanism for non-replication of allelic association between a single nucleotide polymorphism of the human beta T-cell receptor and autoimmune diseases

2008 ◽  
Vol 35 (2) ◽  
pp. 141-144 ◽  
Author(s):  
P. Tripputi ◽  
S. Bianchi ◽  
L. Fedele
2022 ◽  
Vol 14 (1) ◽  
Author(s):  
Aviv Omer ◽  
Ayelet Peres ◽  
Oscar L Rodriguez ◽  
Corey T Watson ◽  
William Lees ◽  
...  

Abstract Background T and B cell receptor (TCR, BCR) repertoires constitute the foundation of adaptive immunity. Adaptive immune receptor repertoire sequencing (AIRR-seq) is a common approach to study immune system dynamics. Understanding the genetic factors influencing the composition and dynamics of these repertoires is of major scientific and clinical importance. The chromosomal loci encoding for the variable regions of TCRs and BCRs are challenging to decipher due to repetitive elements and undocumented structural variants. Methods To confront this challenge, AIRR-seq-based methods have recently been developed for B cells, enabling genotype and haplotype inference and discovery of undocumented alleles. However, this approach relies on complete coverage of the receptors’ variable regions, whereas most T cell studies sequence a small fraction of that region. Here, we adapted a B cell pipeline for undocumented alleles, genotype, and haplotype inference for full and partial AIRR-seq TCR data sets. The pipeline also deals with gene assignment ambiguities, which is especially important in the analysis of data sets of partial sequences. Results From the full and partial AIRR-seq TCR data sets, we identified 39 undocumented polymorphisms in T cell receptor Beta V (TRBV) and 31 undocumented 5 ′ UTR sequences. A subset of these inferences was also observed using independent genomic approaches. We found that a single nucleotide polymorphism differentiating between the two documented T cell receptor Beta D2 (TRBD2) alleles is strongly associated with dramatic changes in the expressed repertoire. Conclusions We reveal a rich picture of germline variability and demonstrate how a single nucleotide polymorphism dramatically affects the composition of the whole repertoire. Our findings provide a basis for annotation of TCR repertoires for future basic and clinical studies.


2011 ◽  
Vol 75 (3) ◽  
pp. 359-369 ◽  
Author(s):  
Shin-Hwa Lee ◽  
Hun Soo Chang ◽  
An-Soo Jang ◽  
Sung-Woo Park ◽  
Jong Sook Park ◽  
...  

2004 ◽  
Vol 44 (7) ◽  
pp. 669 ◽  
Author(s):  
W. Barendse ◽  
R. Bunch ◽  
M. Thomas ◽  
S. Armitage ◽  
S. Baud ◽  
...  

The TG5 (thyroglobulin 5′ leader sequence) single nucleotide polymorphism has been associated with marbling in cattle fed for periods longer than 250 days. To test whether the association could be detected in diverse cattle, fed for less than 250 days, and to measure the size of the effect, we sampled 1750 cattle from the AMH Toowoomba feedlot. These cattle were sampled on 28 separate days, over 9 months. Their marbling scores covered the complete range. We found that the TG5 single nucleotide polymorphism was associated with marbling scores (P<0.05) and estimated that TG5 genotypes explained 6.5% of the residual deviance for the marbling phenotype. We also found that the '3' allele was more frequent in animals with higher marbling scores. The consistency of the allelic association between studies and, in particular, the association found in diverse cattle, indicate that the TG5 polymorphism can be used as a breeding tool and possibly a feedlot entry tool. To estimate the size of the genetic region in which the marbling quantitative trait loci are located, we tested the nearby DNA markers CSSM66 and BMS1747. These do not show allelic associations to marbling. The consistency of the allelic association between studies, the lack of association to nearby DNA markers and the complementary information on gene action of genes near Thyroglobulin suggest that DNA sequence variations, in or near the Thyroglobulin gene sequence, are the likely causes for the marbling quantitative trait loci. Further studies of single nucleotide polymorphism in and near the Thyroglobulin DNA sequence should allow causal mutations for the effect to be identified.


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