A “silent” nucleotide substitution in exon 4 is responsible for the “alternative expression” of HLA-A*01:01:38L through aberrant splicing

Dunn, P. P. J.; Hammond, Laura; Coates, E.; Street, J.; Griner, Leon; Darke, C.

doi:10.1016/j.humimm.2011.05.019

Cited by 12 publications

(13 citation statements)

References 29 publications

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“…For example, a silent mutation in the MDR1 gene results in decreased levels of mRNA by a change in mRNA stability, thus altering the protein level(Wang et al , 2005). Another example is a synonymous SNP in exon 4 of the human leukocyte antigen (HLA)-A2 gene, which results in the alternative expression of HLA-A*01:01:38L through aberrant splicing (Dunn et al ., 2011). In addition, the presence of a rare codon, marked by a silent mutation, can affect the translation rate as a result of the scarcity of cognate tRNA, which in turn influences the cotranslational folding and/or insertion of a protein into the membrane, thereby altering the conformation and function of the protein (Kimchi-Sarfaty et al , 2007; Komar, 2007).…”

Section: Discussionmentioning

confidence: 99%

Genetic diversity of Toll-like receptor 5 among pig populations

Yang

Qing-zhi

et al. 2013

Genet. Mol. Biol.

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The Toll-like receptor 5 (TLR5) recognizes flagellin of Gram-positive and -negative bacteria and plays an important role in the host defense system. Here, we surveyed single nucleotide polymorphisms (SNPs) in the coding sequence of the porcine TLR5 gene in 83 individuals from five pig breeds, these including Chinese local populations and Western commercial pig breeds. A total of 19 medium polymorphic SNPs (0.25 < PIC < 0.5) were identified, three of which were missense mutations that clustered within the extracellular domain of TLR5. One of the non-synonymous SNPs fell within a 228-amino acid region which has been shown to be important for flagellin recognition. Four SNPs were only found with high frequencies in Oriental pig breeds. The 19 SNPs were found in 30 haplotypes, one of which segregated at high frequency in all samples. Compared with Western pig breeds, Chinese local populations had higher genetic diversity and more haplotypes. Tajima’s test showed no evidence for deviation from neutrality. The data provide useful information for future genetic marker characterization by means of disease association analysis and/or stimulating the mutation carrier with relevant ligands.

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Section: Discussionmentioning

confidence: 99%

Genetic diversity of Toll-like receptor 5 among pig populations

Yang

Qing-zhi

et al. 2013

Genet. Mol. Biol.

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“…An SNP overlooked in an intron by this method is only relevant if it affects expression through an effect on splicing. The only expression variant we have sequenced from RNA was HLA‐A*01:01:38L, which has a truncated exon 4 characteristic of this low‐expression allele (Dunn et al. , 2011).…”

Section: Rna Sbtmentioning

confidence: 99%

“…, 2011). Normal‐sized exon 4 is observed if the A*01 gene is sequenced from amplified genomic DNA (Dunn et al. , 2011).…”

Section: Rna Sbtmentioning

confidence: 99%

Human leucocyte antigen typing: techniques and technology, a critical appraisal

Dunn¹

2011

Int J Immunogenetics

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Methods for the identification of Human Leukocyte Antigens (HLA) have changed significantly since this group of polymorphic proteins were first characterized by serological reagents in the 1960s and 1970s. The invention and development of the Polymerase Chain Reaction (PCR) has been key in the progress of methods for HLA genotyping. As the complexity of HLA polymorphism has unravelled so it has exposed the weaknesses in techniques such as PCR - Restriction Fragment Length Polymorphism (RFLP) and Reference Strand Mediated Conformation Analysis (RSCA), which are no longer in use today. Methods which have been considered routine laboratory tools in recent years, such as Sequence-Specific Primer - PCR and Sequencing Based Typing (SBT) are now also threatened with extinction, not only because of the depth of HLA variation but also because of the rapid development of Next Generation Sequencing and technologies which will follow this. This review describes the merits and disadvantages of current technologies available to HLA Typing laboratories, future trends and the problems posed by new alleles.

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“…Likewise, limited data are available regarding the functional or clinical impact of outsidethe-groove variability. It has been shown that some of these polymorphisms can influence HLA surface expression by transcriptional regulation, alternative splicing or structural changes of the molecule [11][12][13], while others did not change the repertoire of bound peptides [14]. From the clinical side, a polymorphism in exon 3 of DRB1 Ã 14:01/14:54 was shown not to have a significant impact on the outcome of unrelated VUD-HSCT [15,16].…”

Section: Introductionmentioning

confidence: 99%