Delineation of additional genetic bases for C8 beta deficiency: prevalence of null alleles and predominance of C-->T transitions in their genesis

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Journal of Immunology




We studied the molecular bases for C8 beta deficiency in 34 unrelated families from the United States and the former Soviet Union. These families represented 69 unrelated null alleles of which 59 (86%) were found to be due to a previously described C-->T transition in exon 9. Six additional null alleles were also caused by C-->T transitions, of which four (6%) were located at base 388 in exon 3, one (2%) at base 298 in exon 3, and one (2%) involved cytosine 847 in exon 6. All of the null alleles affecting cytosine 388 were linked to the sequence polymorphism at base 376, which determines the uncommon C8 beta acidic allotype. Two null alleles were caused by single base pair deletions of cytosines at positions 430 and 632 in exons 3 and 5, respectively. Of the characterized null alleles, 97% were due to C-->T transitions in which an arginine (64 alleles) or a glutamine (one allele) was replaced by a stop codon. The basis for this apparent high frequency of C-->T transitions occurring in a relatively short stretch of DNA is uncertain.