Am J Hum Genet 31:630- 633, 1979
Brief Communication Assignment of the Red Cell Antigen, Targett (Rh4O), to the Rh Blood Group System M. LEWIS,' H. KAITA,1 P. W. ALLDERDICE,2 S. BARTLETT,2 W. G. SQUIRES,3 AND R. G. HUNTSMAN2'4
SUMMARY
Statistical and serological evidence from a large kindred and two unrelated adults indicates that Targett (Tar) is an antigen in the Rh blood group system and that its presence is associated with a weak expression of the Rh antigen D. In the numerical notation the Tar antigen is designated Rh4O.
A new low incidence blood group antigen, Targett, was described in 1975. The data indicated it to be inherited as an autosomal dominant, independently of the ABO, MNSs, and Kell blood group systems [1]. This paper presents evidence for the assignment of the antigen, hereafter referred to as Tar, to the Rh blood group system. With the consent of Peter Issitt, University of Cincinnati, the numerical notation is specified as Rh40. Those preferring this notation should read the text substituting Rh40 for Tar, anti-Rh40 for anti-Tar, Rh:40 for Tar +, and Rh: -40 for Tar-.
Received January 11, 1979. This work was supported by grants MA-3391 and' MA-5724 from the Medical Research Council of Canada, and was presented in part by poster session at the 29th annual meeting of the American Society of Human Genetics in Vancouver, B.C., October 1978. 1 Department of Pediatrics, University of Manitoba, and Rh Laboratory, Health Sciences Center, 735 Notre Dame Ave., Winnipeg, Manitoba, R3E OL8, Canada. 2 Faculty of Medicine, Memorial University of Newfoundland, St. John's. 3Sir Thomas Roddick Hospital, Stephenville, Newfoundland. I Canadian Red Cross Blood Transfusion Service, St. John's, Newfoundland. © 1979 by the American Society of Human Genetics. 0002-9297/79/3105-0004$00.75
630
RED CELL ANTIGEN, TARGETT
631
MATERIALS AND METHODS
Following its discovery, the antigen Tar was included as a marker in families being examined for genetic linkages. Shortage of the antiserum (anti-Tar) coupled with the low incidence of the antigen (three Tar + reported among 612 British Columbia Red Cross blood donors [1]), necessitated the restriction of testing to samples from parents: two of 900 were Tar +. Consequent to the observation that these two samples gave atypical expression of the Rh antigen D, assessment of D expression was included in tests on samples from family members of generations I and 11 here reported. (A delay in transit rendered samples from generation ll1 members useless for refined testing.) The expression of the D antigen was measured by speed of reaction with saline-active anti-sera in the capillary tube, a method we have used extensively in the study of characterization and dosage of Rh antigens [2]. RESULTS
The Rh and Tar types for members of Family Nic are depicted in figure 1. The family comes from a small inbred community, so we assume that the origin of Tar in 11-3 is the same as that for I- 1, although details of the relationship have not yet been obtained. Inspection of the phase-known nuclear families in figure 1 reveals that generation III members who are Tar + carry the grandpaternal R1 and that those who have inherited the grandmaternal r are Tar -. There are thus eight nonrecombinants (NR) between Tar and Rh in generation III: lods + 2.408 at 0 .00. The z count of 3:0 provided by the offspring of 11-3 boosts the lods to + 3.01. Observations relative to expression of the D antigen are in table 1. The anti-D serum Ber is our current routine typing serum; the time interval between D homozygotes, regardless of Tar type, and Tar -, D heterozygotes is slight, that between Tar + and Tar -, D heterozygotes is striking. This observation during initial typing suggested that the Rh alleles of I- 1 might be differentiated. The sera Lei and Sho were selected for further studies because we have used them extensively since 1953 and because they were key sera in similar studies resulting in the assignments of the low incidence antigens Wiel (DW) and Gonzales (Goa) to the Rh system [3, 4]. With Lei and Sho it is clear that the cells of I-1 do not give the reactions of an ordinary D homozygote. For brevity, only one control is listed in the table. All three anti-D sera show that the R', Tar - allele inherited by 11-4 can be distinguished from the R1, Tar + allele inherited by her siblings. On this basis, generation II provides a z count of 6:0, giving lods of + 1.505 at 0 .00. I
1 a_
2 ~~~~1
R1 /R1 iI1
) r
|r Rir
1D 21 3 14
r/r TARdRh
r/r 3 NR
r/r RIR
R
r/
T 1t
345 Rir
r/r
r
5 °6
r/r
| R2/r
R
RI/R1
Rir
R1/R2 R2/r 2 NR
Rir
11 0
9
7
r/r
~
1~11
9
NT
R1/r
1 NR
'IT
13 11
12
1
Ri r
13 R
5-
R/R
R/
rir
1 /r
JA0151
R1/R1
NT
1
R1/r
2 NR
FIG. 1. -TAR (RH40) and Rh types of Family Nic./= deceased; CC = Tar + (Rh:40); ZO = Tar (Rh: -40); NT = not tested; NR = nonrecombinant.
LEWIS ET AL.
632
TABLE 1
STRENGTH OF D ANTIGEN MEASURED BY SPEED OF REACTION (IF ANY) WITH SELECTED SALINE-ACTIVE ANTI-D SERA BY CAPILLARY METHOD REACTION TIME WITH ANTI-D* (IN MIN) PHENOTYPE OR GENOTYPE
TAR(RH40)
Ber
Lei
Sho
Control ............. I-1 ............... Control .............
R1/R1 R1/R1
+ -
12
4
21 21
8
11-4
R1r
12 14 14 14 75
RED CELL SOURCE
...............
11-2,3,7,9,11,13 ..... Control .............
R1r R1Ir r'/r
_ +
-
21 60
8 8 -
-
* As mentioned in the text, we have had long use of these antisera. Only one control of each type is listed, as the times recorded are those regularly observed. The speed of reaction reflects the strength of antigen expression. - = negative.
No atypical reactions were noted for other Rh antigens or for antigens of other blood group systems. I- I is negative for the low incidence Rh antigens CW, CX, RN, Dw, Go2, EW, V, VS, and Be2. We do not have the reagent to test his cells for Evans [5], but anti-Tar does not react with Evans + cells [1]. Tests with representative samples from D+ people who have produced anti-D classified according to Tippett [6] indicate that Tar is not definitive of categories III, IV, V. or VI, although the possibility that it defines a new or subcategory cannot be eliminated. DISCUSSION
The weakened expression of the D antigen in the presence of Tar is not peculiar to the Nic family. As mentioned above, both of the Tar + samples found in the 900 parents gave atypical D expression. (The family of the other propositus [phenotype Rl/r] has not yet become available for study.) Further, a Tar +, Rl/r sample referred by Miss N. Wheeler (Gamma Biologicals, Houston) gave D timings identical with those shown for the Tar +, R1Ir samples in table 1. The sample, actually Miss Wheeler's own blood, was submitted specifically for Tar testing, because following its circulation in a proficiency testing program, she received conflicting D typings from participating laboratories, an eventuality which can be predicted from the results in table 1. The lods at 6 .00 of at least + 3.01 and probably + 4.515 indicate that Tar is governed by a locus either closely linked to or the same as Rh. The altered expression of the D antigen in three unrelated propositi strongly favors inclusion of the Tar antigen in the Rh blood group system. ACKNOWLEDGMENTS We are much indebted to Dr. T. D. Stout for supplying us with anti-Tar serum and to Miss N. Wheeler for permission to mention the tests with her blood sample.
REFERENCES I. HUMPHREYS J, STOUT TD, KAITA H, CHOWN B: A new blood group antigen, Targett. Proceedings International Congress of Blood Transfusion. Helsinki, July, 1975 2. CHOWN B, LEWIS M, KAITA H: The inheritance of the Rh blood groups. ii Expression of
RED CELL ANTIGEN, TARGETT
633
the Rh antigens in random unrelated Caucasian families. Vox Sang 21:126-134, 1971 3. CHOWN B, LEWIS M, KAITA H: A new Rh antigen and antibody. Transfusion 2:150- 154, 1962 4. LEWIS M, CHOWN B, KAITA H et al.: Blood group antigen Goa and the Rh system. Transfusion 7:440-441, 1967 5. CONTRERAS M, STEBBING B, BLESSING M, GAVIN J: The Rh antigen Evans. Vox Sang
34:208-211, 1978 6. RACE RR, SANGER R: Blood Groups in Man, 6th ed. Oxford, Blackwell, 1975, p 191
International Congress on Cystic Fibrosis The Eighth International Congress on Cystic Fibrosis will be held at the Royal York Hotel in Toronto, May 26 - 30, 1980. For a brochure and further information, write to Congress Secretariat, c/o Conference Management Associates, 191 College St., Toronto, Ontario M5T 1P7, Canada.
Brief Communication Assignment of the Red Cell Antigen, Targett (Rh4O), to the Rh Blood Group System M. LEWIS,' H. KAITA,1 P. W. ALLDERDICE,2 S. BARTLETT,2 W. G. SQUIRES,3 AND R. G. HUNTSMAN2'4
SUMMARY
Statistical and serological evidence from a large kindred and two unrelated adults indicates that Targett (Tar) is an antigen in the Rh blood group system and that its presence is associated with a weak expression of the Rh antigen D. In the numerical notation the Tar antigen is designated Rh4O.
A new low incidence blood group antigen, Targett, was described in 1975. The data indicated it to be inherited as an autosomal dominant, independently of the ABO, MNSs, and Kell blood group systems [1]. This paper presents evidence for the assignment of the antigen, hereafter referred to as Tar, to the Rh blood group system. With the consent of Peter Issitt, University of Cincinnati, the numerical notation is specified as Rh40. Those preferring this notation should read the text substituting Rh40 for Tar, anti-Rh40 for anti-Tar, Rh:40 for Tar +, and Rh: -40 for Tar-.
Received January 11, 1979. This work was supported by grants MA-3391 and' MA-5724 from the Medical Research Council of Canada, and was presented in part by poster session at the 29th annual meeting of the American Society of Human Genetics in Vancouver, B.C., October 1978. 1 Department of Pediatrics, University of Manitoba, and Rh Laboratory, Health Sciences Center, 735 Notre Dame Ave., Winnipeg, Manitoba, R3E OL8, Canada. 2 Faculty of Medicine, Memorial University of Newfoundland, St. John's. 3Sir Thomas Roddick Hospital, Stephenville, Newfoundland. I Canadian Red Cross Blood Transfusion Service, St. John's, Newfoundland. © 1979 by the American Society of Human Genetics. 0002-9297/79/3105-0004$00.75
630
RED CELL ANTIGEN, TARGETT
631
MATERIALS AND METHODS
Following its discovery, the antigen Tar was included as a marker in families being examined for genetic linkages. Shortage of the antiserum (anti-Tar) coupled with the low incidence of the antigen (three Tar + reported among 612 British Columbia Red Cross blood donors [1]), necessitated the restriction of testing to samples from parents: two of 900 were Tar +. Consequent to the observation that these two samples gave atypical expression of the Rh antigen D, assessment of D expression was included in tests on samples from family members of generations I and 11 here reported. (A delay in transit rendered samples from generation ll1 members useless for refined testing.) The expression of the D antigen was measured by speed of reaction with saline-active anti-sera in the capillary tube, a method we have used extensively in the study of characterization and dosage of Rh antigens [2]. RESULTS
The Rh and Tar types for members of Family Nic are depicted in figure 1. The family comes from a small inbred community, so we assume that the origin of Tar in 11-3 is the same as that for I- 1, although details of the relationship have not yet been obtained. Inspection of the phase-known nuclear families in figure 1 reveals that generation III members who are Tar + carry the grandpaternal R1 and that those who have inherited the grandmaternal r are Tar -. There are thus eight nonrecombinants (NR) between Tar and Rh in generation III: lods + 2.408 at 0 .00. The z count of 3:0 provided by the offspring of 11-3 boosts the lods to + 3.01. Observations relative to expression of the D antigen are in table 1. The anti-D serum Ber is our current routine typing serum; the time interval between D homozygotes, regardless of Tar type, and Tar -, D heterozygotes is slight, that between Tar + and Tar -, D heterozygotes is striking. This observation during initial typing suggested that the Rh alleles of I- 1 might be differentiated. The sera Lei and Sho were selected for further studies because we have used them extensively since 1953 and because they were key sera in similar studies resulting in the assignments of the low incidence antigens Wiel (DW) and Gonzales (Goa) to the Rh system [3, 4]. With Lei and Sho it is clear that the cells of I-1 do not give the reactions of an ordinary D homozygote. For brevity, only one control is listed in the table. All three anti-D sera show that the R', Tar - allele inherited by 11-4 can be distinguished from the R1, Tar + allele inherited by her siblings. On this basis, generation II provides a z count of 6:0, giving lods of + 1.505 at 0 .00. I
1 a_
2 ~~~~1
R1 /R1 iI1
) r
|r Rir
1D 21 3 14
r/r TARdRh
r/r 3 NR
r/r RIR
R
r/
T 1t
345 Rir
r/r
r
5 °6
r/r
| R2/r
R
RI/R1
Rir
R1/R2 R2/r 2 NR
Rir
11 0
9
7
r/r
~
1~11
9
NT
R1/r
1 NR
'IT
13 11
12
1
Ri r
13 R
5-
R/R
R/
rir
1 /r
JA0151
R1/R1
NT
1
R1/r
2 NR
FIG. 1. -TAR (RH40) and Rh types of Family Nic./= deceased; CC = Tar + (Rh:40); ZO = Tar (Rh: -40); NT = not tested; NR = nonrecombinant.
LEWIS ET AL.
632
TABLE 1
STRENGTH OF D ANTIGEN MEASURED BY SPEED OF REACTION (IF ANY) WITH SELECTED SALINE-ACTIVE ANTI-D SERA BY CAPILLARY METHOD REACTION TIME WITH ANTI-D* (IN MIN) PHENOTYPE OR GENOTYPE
TAR(RH40)
Ber
Lei
Sho
Control ............. I-1 ............... Control .............
R1/R1 R1/R1
+ -
12
4
21 21
8
11-4
R1r
12 14 14 14 75
RED CELL SOURCE
...............
11-2,3,7,9,11,13 ..... Control .............
R1r R1Ir r'/r
_ +
-
21 60
8 8 -
-
* As mentioned in the text, we have had long use of these antisera. Only one control of each type is listed, as the times recorded are those regularly observed. The speed of reaction reflects the strength of antigen expression. - = negative.
No atypical reactions were noted for other Rh antigens or for antigens of other blood group systems. I- I is negative for the low incidence Rh antigens CW, CX, RN, Dw, Go2, EW, V, VS, and Be2. We do not have the reagent to test his cells for Evans [5], but anti-Tar does not react with Evans + cells [1]. Tests with representative samples from D+ people who have produced anti-D classified according to Tippett [6] indicate that Tar is not definitive of categories III, IV, V. or VI, although the possibility that it defines a new or subcategory cannot be eliminated. DISCUSSION
The weakened expression of the D antigen in the presence of Tar is not peculiar to the Nic family. As mentioned above, both of the Tar + samples found in the 900 parents gave atypical D expression. (The family of the other propositus [phenotype Rl/r] has not yet become available for study.) Further, a Tar +, Rl/r sample referred by Miss N. Wheeler (Gamma Biologicals, Houston) gave D timings identical with those shown for the Tar +, R1Ir samples in table 1. The sample, actually Miss Wheeler's own blood, was submitted specifically for Tar testing, because following its circulation in a proficiency testing program, she received conflicting D typings from participating laboratories, an eventuality which can be predicted from the results in table 1. The lods at 6 .00 of at least + 3.01 and probably + 4.515 indicate that Tar is governed by a locus either closely linked to or the same as Rh. The altered expression of the D antigen in three unrelated propositi strongly favors inclusion of the Tar antigen in the Rh blood group system. ACKNOWLEDGMENTS We are much indebted to Dr. T. D. Stout for supplying us with anti-Tar serum and to Miss N. Wheeler for permission to mention the tests with her blood sample.
REFERENCES I. HUMPHREYS J, STOUT TD, KAITA H, CHOWN B: A new blood group antigen, Targett. Proceedings International Congress of Blood Transfusion. Helsinki, July, 1975 2. CHOWN B, LEWIS M, KAITA H: The inheritance of the Rh blood groups. ii Expression of
RED CELL ANTIGEN, TARGETT
633
the Rh antigens in random unrelated Caucasian families. Vox Sang 21:126-134, 1971 3. CHOWN B, LEWIS M, KAITA H: A new Rh antigen and antibody. Transfusion 2:150- 154, 1962 4. LEWIS M, CHOWN B, KAITA H et al.: Blood group antigen Goa and the Rh system. Transfusion 7:440-441, 1967 5. CONTRERAS M, STEBBING B, BLESSING M, GAVIN J: The Rh antigen Evans. Vox Sang
34:208-211, 1978 6. RACE RR, SANGER R: Blood Groups in Man, 6th ed. Oxford, Blackwell, 1975, p 191
International Congress on Cystic Fibrosis The Eighth International Congress on Cystic Fibrosis will be held at the Royal York Hotel in Toronto, May 26 - 30, 1980. For a brochure and further information, write to Congress Secretariat, c/o Conference Management Associates, 191 College St., Toronto, Ontario M5T 1P7, Canada.
