title: Allelic polymorphism in the coding region of human TCR C alpha gene and characterization of structural variability in the alpha chain constant domain.
abstract: 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.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Immunology, Fundación Jiménez Díaz, Madrid, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Bragado
authors.forename: A
authors.initials: A
authors.lastname: García
authors.forename: M A
authors.initials: MA
authors.lastname: Treviño
authors.forename: C
authors.initials: C
authors.lastname: Vilches
authors.forename: J A
authors.initials: JA
authors.lastname: López de Castro
mesh_terms: D000483:Alleles; D001483:Base Sequence; D002999:Clone Cells; D006801:Humans; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D013030:Spain
chemical_list: D016693:Receptors, Antigen, T-Cell, alpha-beta