Definition of new alleles of MIC‐A using sequencing‐based typing

Abstract

We have sequenced exons 2, 3 and 4 of MIC‐A in 23 homozygous cell lines, 22 families and 54 unrelated individuals. This has led to the definition of seven polymorphic positions in exon 2, 13 in exon 3 and 12 in exon 4, yielding a total of 33 different MIC‐A allelic specificities, of which 16 have not been described before. The newly defined sequences and those of the alleles defined before were entered into a database of the SCORE program (Helmberg et al., 1998, Tissue Antigens, 51, 587) for comprehensive genotyping analysis. In the tested sample, only one genotype present in two individuals gave rise to an ambiguous genotype. If all possible combinations of the 33 alleles are considered, 10 of 636 combinations are ambiguous. The MIC‐A exon 2, 3 and 4 polymorphism is characterized by diallelic single base exchanges and by a considerable degree of exon shuffling. The majority of heterozygote positions identified are non‐synonymous, i.e. five of seven in exon 2, 13 of 13 in exon 3 and eight of 12 in exon 4, suggesting an important function for the MIC‐A polymorphism.

Cytokine gene polymorphism in human disease: on-line databases

“…Cytokine and cytokine receptor genes are generally highly conserved in terms of exon sequences, 32,33 although examples of amino acid sequence variation have been found for IL-4 receptor, LT␣ (TNF␤), TGF␤ and GM-CSF receptor ␤ in healthy individuals; and in the IL-2 receptor ␥ gene for persons with severe combined immunodeficiency (Tables 1 and 3). Although conservative (silent) mutations do not affect amino acid sequence, they may influence protein expression in a variety of other ways: for example, they can alter mRNA splicing, mRNA stability, and levels of gene transcription.…”

“…Finally, they may alter binding sites within the nuclear matrix for architectural transcription factors which modulate promoter geometry. 34 Many of the reported polymorphisms within cytokine genes occur within known or putative regulatory regions 32,33 (Table 1). The rationale for studying cytokine gene polymorphisms in human disease can be broadly summarised as follows: • To enhance the understanding of the aetiology and pathology of human disease.…”

The role of tumor necrosis factor-alpha -308 G/A and transforming growth factor-beta 1 -915 G/C polymorphisms in childhood idiopathic thrombocytopenic purpura

“…Researches have shown that polymorphisms in the TNF-α gene at position -308 and -238 affect gene transcription with increased TNF-α production [5,6]. The transcriptionally more active allele of TNF-α (allele 2 of -308) was less frequently observed in pediatric chronic ITP patients than in healthy controls [7].…”

Identification of novel single nucleotide polymorphisms in intron 1B and exon 1C of the human interleukin-1 receptor type I (IL-1RI) gene

“…This confirms the predicted polymorphism at this site based on previous alignment of genomic DNA sequences. 5 Allele frequencies were determined in a population of 46 male and 45 female healthy Caucasian volunteer blood donors from the South West of England using PCR-SSCP (Figure 2a …”