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Leaky Scanning02:28

Leaky Scanning

During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA.  Marilyn Kozak discovered that the sequence RCCAUGG (where R stands for...

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A novel HLA-B*40 sequence--B*40:92.

J Street1, J Johnson, L Hammond

  • 1Welsh Transplantation and Immunogenetics Laboratory, Welsh Blood Service, Pontyclun, Wales, UK.

International Journal of Immunogenetics
|January 7, 2011
PubMed
Summary
This summary is machine-generated.

A novel human leukocyte antigen (HLA) allele, HLA-B*40:92, was discovered in a European donor. This new allele likely arose from a gene conversion event and exhibits unique serological reactivity, potentially impacting hematopoietic stem cell transplantation matching.

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Area of Science:

  • Immunogenetics
  • Molecular Biology
  • Human Leukocyte Antigen (HLA) System

Background:

  • The Human Leukocyte Antigen (HLA) system is crucial for immune response and transplantation compatibility.
  • Identification of novel HLA alleles is essential for refining donor matching and understanding immune diversity.
  • Previous typing methods have limitations in detecting rare or newly emerged HLA variants.

Purpose of the Study:

  • To report the discovery and initial characterization of a novel HLA-B allele, designated HLA-B*40:92.
  • To investigate the molecular basis and potential evolutionary origin of HLA-B*40:92.
  • To determine the serological characteristics and haplotype association of the novel HLA-B*40:92 allele.

Main Methods:

  • Polymerase chain reaction using sequence-specific priming (PCR-SSP) for HLA typing of hematopoietic stem cell (HSC) donors.
  • Nucleotide sequencing of exon 3 to identify genetic variations.
  • Analysis of amino acid substitutions and potential gene conversion events.
  • Serological testing using antisera and monoclonal trays to define B*40:92 reactivity.
  • Haplotype analysis to determine linkage with other HLA loci.

Main Results:

  • A new HLA allele, HLA-B*40:92, was identified in a north-western European HSC donor.
  • HLA-B*40:92 differs from HLA-B*40:01:01 by six nucleotide substitutions in exon 3, resulting in four amino acid changes and one silent substitution.
  • The genetic profile suggests a gene conversion or interallelic recombination event involving HLA-B*40:01:01 and potentially HLA-B*15 or HLA-B*35 alleles.
  • Serological testing revealed that HLA-B*40:92 possesses a 'short' B40/B60 specificity with some HLA-B35 reactivity.
  • The allele was found on a specific haplotype and its frequency in the studied population was determined to be very low (0.00001).

Conclusions:

  • HLA-B*40:92 represents a newly identified allele within the HLA-B locus, likely originating from recombination events.
  • The unique amino acid substitutions and resulting serological profile of HLA-B*40:92 are characterized.
  • This discovery underscores the importance of continuous HLA typing for identifying rare alleles relevant to transplantation and immunological studies.
  • An Epstein-Barr virus transformed B-cell line from the donor is available for further research.