Genetics of the HL‐A System A Population and Family Study

Abstract

A total of 973 unrelated Danes and Norwegians have been typed for a number of HL-A iso-antigens, and so have 150 Danish and Norwegian families with a total of 480 children. Two series of HL-A iso-antigens were investigated: the LA series with the antigens HL-Al, 2,3, Ba *, ILN * and LA4, and the Four series with the antigens HL-A5,7,8, T12, R *, HN, FJH and BB. These antigens were inherited as co-dominant characters with the exception of Ba *, ILN *, and R *, which were operationally recessive to HL-A2, 3 and 5, respectively, but co-dominant in respect of the other factors. No individuals carried more than two antigens from each series, and the family analysis yielded no evidence against the assumption that the antigens within each series are controlled by mutually exclusive genetic determinants: The LA and Four series represent two mutational sites within the HL-A chromosomal region. No recombinations between these series were observed in this study, and the estimated upper limit of the recombination frequency between the corresponding sites was 0.84%. A total of 345 parental haplotypes could be unequivocally deduced; two of these, HL-A (1, 8) and HL-A (3, 7), occurred much oftener than should have been expected from the frequencies of the corresponding determinants, and there is thus linkage disequilibrium between the LA and Four series.In 1965, DAUSSET et al. [7] postulated on the basis of population data that most human leukocyte iso-antigens belong to one system. Family data supporting this assumption was presented by VAN ROOD et al. in 1966 [20b], and in 1967 the final proof was obtained [l, 4, 5,8,211. This system,, is one of the most complex immunogenetic systems known t o exist in man. At the present time, our knowledge of the chromosomal arrangement of its many genetic determinants is increasing rapidly. PAYNE, BODMER and their coworkers [19] had already in 1964 defined two leukocyte antigens, LA1 (HL-A1) and LA2 (HL-A2), which are controlled by alleles, and two years later they [2] added a new allele, LA3 (HL-A3), to 98 SVEJCAARD et al. Genetics of the HL-A System this series, which we now call the LA series (= '1st sublocus' of DAUSSET et al. [9]). These observations were confirmed in 1967 by DAUSSET et al. [8] and CEPPELLINI et al. [4]. The latter authors also found evidence in favour of the existence within the HL-A system of another series (Four = '2nd sublocus' of DAUSSET et al. [9]) of mutually exclusive genetic determinants : To5 (HL-AS), To7 (HL-A8) and Toll ( K N -T l 2 ) ; DAUSSET et al. [7] had previously observed that none of 133 individuals carried more than two of three antigens corresponding t o these Torino determinants, and two antigens from the 7-series of VAN ROOD et al. [20a], 6C = 7C (HL-A7) and 7D (HL-A8), belong also to the Four series. During 1968-69, several reports [9,11,12,22,29,31] confirmed and extended the findings O f CEPPELLINI et al. [4], and evidence was presented [ll, 12,291 that each of the highfrequency antigens 4A and 4B of VAN ROOD et al. [21] consists of narrowe...

Complement-Fixing Platelet Iso-Antibodies V. HL-A Typing

“…The BB specificity was originally defined as a platelet antigen and has later been shown to belong to the Four series [16]. At the present time, several HL-A antigens are recognizable only in the lymphocytotoxic test, but it seems likely that most, if not all, HL-A specifi cities may eventually become detectable on platelets when suitable reagents become available.…”

“…It seems to detect HL-A iso-antigens identical with those found in the lymphocytotoxic test, which is the most commonly applied technique at the present time. These antigens belong to two series, LA and Four, each of which represents a mutational site within the HL-A chromosomal region [6,16].…”

Linkage and Association Studies of Two Phosphoglucomutase Loci (PGM₁ and PGM₃) to Eighteen Other Markers Analysis of the Segregation at the Marker Loci

“…In the scoring of the HL-A locus, the LA and the Four series of determinants were regarded as belonging to one locus. This does not seriously bias the estimate ofco, for although recombination has been found [K issmeyerNielsen el al., 1969], the analysis of two series of consecutive infor mative families [Svejgaard et al, 1970] has shown that the recom bination frequency is probably (90%) less than 0.0053. However, to minimize the bias a determinant at the LA locus was always pre ferred for scoring.…”

New HL-A Alleles

“…Each series of antigens seems to be determined by multiple mutually exclusive genes which behave as alleles in population and family studies [2,5,6,13,14,16]. The two loci or sub-loci within the HL-A chromosomal region are closely linked; a maximum recombination frequency of less than 0.53% has been calculated [13].…”

“…Each series of antigens seems to be determined by multiple mutually exclusive genes which behave as alleles in population and family studies [2,5,6,13,14,16]. The two loci or sub-loci within the HL-A chromosomal region are closely linked; a maximum recombination frequency of less than 0.53% has been calculated [13].In a recent paper we reported how the remaining alleles of the HL-A system may be identified with antisera obtained by immuniza tion within selected donor-recipient pairs [16]. The recipients should then preferably contain two well-defined antigens of both sub-loci.…”