科研之友
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摘要
An allelic variant of the human TCR C(alpha) gene, designated C(alpha)AL, which encodes a structurally different protein product has been characterized. C(alpha)AL was independently sequenced using polymerase chain reaction (PCR)-amplified TCR C(alpha) CDNA from various T cell clones derived from a same individual. It differed from the most usual C(alpha) sequence by two non-synonymous base changes at codons 4 (AAC-->AAG) and 84 (GAA-->GCA) of the C(alpha) coding region. These changes imply amino acid substitutions Asn-->Lys and Glu-->Ala respectively. An oligotyping method, based on hybridization of allele-specific oligonucleotides to PCR-amplified C(alpha) DNA, is also described. It was used for differential typing of the two C(alpha) forms in family and population studies. In each of three T cell clones analyzed from the same donor having two rearranged TCR alpha chain transcripts, C(alpha)AL was found in only one of the transcripts. In addition, C(alpha)AL segregated as a co-dominant mendelian allele within the family of this donor. Population analysis was carried out in 73 spanish individuals. Twelve donors (16.4%) were heterozygous, implying that C(alpha)AL was present in this population sample with an allelic frequency of 0.08, The observed frequencies of C(alpha) genotypes were those expected for the two alleles being in Hardy -Weinberg equilibrium. This demonstration of structural polymorphism in the constant region of TCR alpha chains provides a useful genetic marker for TCR and disease association studies due to its precise mapping within the C(alpha) coding region, and its significant frequency in the analyzed population. In an analysis of 17 multiple sclerosis patients, the distribution of C(alpha) coding region alleles was virtually the same as in healthy individuals, indicating no preferential association of one C(alpha) coding region allele to this disease in the population examined.
- 出版日期1994-2
