Vox Sang. 37: 286-289 (1979)

Genetic Linkage between the Radin and Rh Blood Group Loci'

Marion Lewis and Hiroko Kaita Rh Laboratory, Health Sciences Center and Department of Pediatrics, University of Manitoba, Winnipeg, Man.

Abstract. Lods of +3.89 at a recombination fraction (0 ) of 0.10 and recombinant:non- recombinant counts of 2: 16 indicate linkage between the Rd and Rh blood group loci. The possibility that Rd is the same as Sc is discussed.

Introduction

The low incidence red cell antigen Radin (Rd), first reported by Rausen et al. (6), is detected by reaction of Radin-positive cells with specific antibody. Following custom and the recommendation of Lundsgaard and Jensen (4) and to allow symbolic differen- tiation between the allele and the locus, in this paper the antigen will be termed Rda and the antibody anti-Rda. Family studies (4-6) have shown Rda to be inherited as an autosomd dominant and to be controlled from a locus distinct from the loci for the ABO, MNSs, P, Rh, Lu, K, Fy, Jk and Yt blood group systems. For the purposes of this report the locus of the gene responsible for Rda production will be designated Rd although the possibility that the locus is ac- tually Sc (Scianna) will be entertained.

1 Work supported by MRC (Canada) Grant MT 3391 and The Children's Hospital of Winnipeg Research Foundation, Inc.

Ascertainment of Rd(at) Propositi

To locate Rd(a+) propositi for linkage studies we have conducted three surveys with anti-Rd* sera. The results are sum- marized in tableI: blood samples in series 1 and 2 were tested by the capillary anti- globulin method with anti-Rda (BGL); those in series 3 were tested by the one-stage papain capillary method with anti-Rda (Bur). Typing of all Rd(a+) in series 3 was confirmed by the capillary antiglobulin meth- od with both antisera.

Incidence of the Rd(at) Phenotype

Data on the incidence of the Rd(a+) phenotype in Danes (4) and in other popula- tions (6) are included in table I; there is no statistical difference between the overall in- cidence for Canadians and for Danes (x* 1.07, p. 0.30). A possible explanation for

Genetic Linkage between the Radin and Rh Blood Group Loci 9R7

Table I. Incidence of Rd(a + 1 phenotype

Population Number Rd(a + ) Incidence Study

Present (1) Canadian parents 770 3 11257 (2) Manitoba Slavs 170 1 1/170 (3) Winnipeg donors 2,864 9 11318

Total 3,804 13 1 /292

Lundsgaard and Jensen (4) Danes 4,933 24 1 I205

Rausen et a/ . (6) New York Jewish 562 3 1/187 Various: compilation 6,773 0 from 5 laboratories

the disparity between these two series and the very large one of Rausen et al. (6) lies in the diversity of racial origin in the last. Amongst our propositi there is a preponder- ance of Slavs; at least 7 of the 12 in series 1 and 3 are known to have Slavic ancestry, 3 of the other 5 have East European an- cestry.

Tnble II. Distribution of Rda phenotypes in fa- milies where at least one parent is Rd(a+)

Mating type Number Children

total Rd(a+) Rd(a-)

Rd(a+)* x Rd(a-) 19 60 31 29 Rd(a+)* x ? 1 5 4 1 Rd(a+) x ? 1 3 3 0

Family Studies

Families of 8 of the propositi have co- operated in this study. Blood samples from all available members of the kindreds were obtained for testing of red cell antigens, red cell enzymes, HLA and serum types. In re- spect to Radin, cross-absorptions and sub- sequent testings were done with cells from representative members of each family to ensure that the same antigen was being rec- ognized in all families. The distribution of the Radin phenotypes in the families, set out in table 11, is in accordance with expec- ta tion.

As pertinent to this report, ten nuclear families in five kindreds were informative for Rd:Rh linkage; in theni Rda segregates

* Known to be heterozygous because of an Rd(a-) child or parent. ? Dead.

with R1, R4 or r. The lods and recombinant: non-recombinant (R:NR) counts are to be found in table I11 where it can be seen that the lods exceed the critical level of +3 at a recombination fraction (0) of 0.10.

Discussion

The failure to find a recombinant be- tween Rd and Rh amongst the 16 candidates in the paternal information was serendipi- tous in that it made the linkage evident but is misleading as to the proximity of the two

288 LewisIKaita ~~ ~~ ~~

Table 111. Lods and R:NR counts for linkage between Rd and Rh loci

Segregation Number Assumed recombination fraction R: NR information

fam. child. 0.05 0.10 0.20 0.30 0.40

Paternal 5 16 +3.86 +3.48 +2.67 +1.78 +0.83 0:8 Maternal 5 17 -0.23 +0.41 +0.78 4 .71 +0.44 2:8

10 33 +3.63 +3.89 +3.45 +2.49 -1-1.27 2:16

loci. In the paternal information provided by the families of Rausen et al. (6) recombina- tion has occurred (z counts 1:1, 1:l and 3:O) as it has in families of Dr. A . Lundsguard analyzed by Fulk et al. (1) who record lods of -0.106 at 0 0.10 and +0.776 at 0 0.30. The information from the first of these re- ports does not refute linkage, that from the second supports it. The data are still too scant for determination of a precise recom- bination fraction but suggest that it is in the neighbourhood of 0.10.

Linkage of Rd with Rh raises the possi- bility that Rda is part of the Scianna blood group system, the Sc locus having been shown to be linked to Rh (2). The likelihood of finding a family informative for Rd and Sc is remote: to date all Rd(a+) cells we have tested have been Sc:1,-2 and all Sc:1,2 cells have been Rd(a-). The only way in which Rd could be proven to be identical with Sc would be by the demonstration of altered expression of one or more of the antigens Rda, Sc*, Scz, in the red cells of a person heterozygous at both loci. On the other hand, differentiation of Rd and Sc may be accomplished by chromosomal localiza- tion. Sc is known to lie between PGM, and R h (3); linkage relationships between Rd and other chromosome 1 loci are being ex-

amined in collaboration with Dr. E. R . Gib- lett and will be reported when the data are adequate for comment.

Acknowledgements

We are most grateful to Dr. Angelyn Konugres and to Ms. Christine Barrasso for gifts of the anti-Rda sera B G L and Bur and to Ms. Catherine Anderson for supplying pilot samples from blood donors. We also acknowledge with pleasure the cheerful cooperation of the families which made this investigation possible.

References

Falk, C. T.; Walker, M. E.; Martin, M. D., and Allen, F. H., Jr.: Autosomal linkages in humans. Ser. haematol. 8: 153 (1975). Lewis, M.; Kaita, H., and Chown, B.: Genetic linkage between the human blood group loci Rh and Sc (Scianna). Am. J. hum. Genet. 28: 619 (1976). Lewis, M.; Kaita, H.; Chown, B.; Giblett, E. R., and Anderson, J. E.: Relative positions of chro- mosome 1 loci Fy, PGM,, Sc, UMPK, Rh, PGD and ENO,. Can. J. Genet. Cytol. 19: 695 (1977). Lundgaard, A. and Jensen, K. G.: Two new examples of anti-Rd. A preliminary report on the frequency of the Rd (Radin) antigen in the Danish population. Vox Sang. 14: 452 (1968).

Genetic Linkage between the Radin and Rh Blood Group Loci 289

5 Race, R. R. and Sanger, R.: Blood groups in Received: April 4, 1979 man; 6th ed., p. 438 (Blackwell, Oxford 1975).

6 Rausen, A.R.; Rosenfield, R.E.; Alter, A.A.; Hakim, S.; Graven, S. N.; Apollon, C. J.; Dall- man, P. R.; Dalziel, J. C.; Konugres, A. A.; Miss M. Lewis, Francis, B.; Gavin, J., and Cleghorn, T. E.: A Rh Laboratory, ‘new’ infrequent red cell antigen Rd (Radin). 735 Notre Dame Avenue, Transfusion 7: 336 (1967). Winnipeg, R3E OL8 (Canada)

Accepted: May 24, 1979