Fraccaro , M.

Hamerton, J.

Lindsten, J.

Polani, P.

Race, R.

Sanger, R.

Archive of European Integration

ί|!Ρ^!^^» GROUP GENES ARE ON THE SHORT ARM E G A L NOTICE This document was prepared under the sponsorship of the Commission of the European Atomic Energy Community (EURATOM). W ÄÄfiiii?» Neither the Eura tom Commission, its contractors nor any person acting on their behalf : Make any warran ty or representation, express or implied, with respect to the accuracy, completeness, or usefulness of the information contained in this document, or t ha t the use of any information, apparatus , method, or process disclosed in this document may not infringe privately owned r ights ; or m - ■ % " ■ ■ — Assume any liability with respect to the use of, or for damages resulting from the use of any information, apparatus , method or process disclosed in this document. The authors;' aansar asm Beted arm The authors' names are listed in alphabetical order This reprint is intended for restricted distribution only. It reproduces, by hind permission of the publisher, an article from ,,NATURE", Vol. 197, No. 4868 ­ 1963, 648­649. For further copies please apply to Fisher, Knight & Co., Ltd, Gainsborough Press, Lattimore Road —■ St. Albans, Hertfordshire (England). Dieser Sonderdruck ist für eine beschränkte Verteilung bestimmt. Die Wiedergabe des vorliegenden in „NATURE", Vol. 197, Nr. 4868 ­1963, 648­649 erschienenen Aufsatzes erfolgt mit freundlicher Geneh­migung des Herausgebers. Bestellungen weiterer Exemplare sind an Fisher, Knight & Co., Ltd., Gainsborough Press, Lattimore Road — St. Albans, Hertfordshire (England), zu richten. Ce tiré­à­part est exclusivement destine à une diffusion restreinte. Il reprend, avec l'aimable autorisation de l'éditeur, un article publié dans « NATURE », Vol. 197, N° 4868 ­ 1963, 648­649. Tout autre exem­plaire de cet article doit être demandé à Fisher, Knight & Co., Ltd., Gainsborough Press, Lattimore Road — St. Albans, Hertfordshire (England). !'>'H ' ^ i m ìtfi ­m irou 3' Questo estratto è destinato esclusivamente ad una diffusione limitata. Esso è stato riprodotto, per gentile concessione dell'Editore, da « NATURE », Voi. 197, N° 4868 ­ 1963, 648­649. Ulteriori copie dell'articolo debbono essere richieste a Fisher, Knight & Co., Ltd., Gainsborough Press, Lattimore Road — St. Albans, Hertfordshire (England). Süfi^ PI S H I Deze overdruk is slechts voor beperkte verspreiding bestemd. Het artikel is. met ­welwillende toestemming van de uitgever overgenomen uit „NATURE", Vol. 197, No. 4868 ­ 1963, 648­649. Meer exemplaren kunnen besteld worden bij Fisher, Knight & Co., Ltd., Gainsborough Press, Lattimore Road — St. Albans, Hertfordshire (England). yjHitJ^tft \ E U R 3 1 1 . e REPRINT EVIDENCE THAT THE Xg BLOOD GROUP GENES ARE ON THE SHORT ARM OF THE X CHROMOSOMES by M. FRACCARO. J.L. HAMERTOX, J. LINDSTEN, P.E. POLANI, R.R. RACE and R. SANGER. European Atomic Energy Community - EURATOM Reprinted from „Nature", Vol. 197, No. 4868 - 1903, pages 648-1549. Summary not available. E U R 3 1 1 . e REPRINT EVIDENCE THAT THE Xg BLOOD GROUP GENES ARE ON THE SHORT ARM OF THE X CHROMOSOMES by M. FRACCARO, J.L. HAMERTOX, J. LINDSTEN, P.E. POLANI, R.R. RACE and R. SANGER. European Atomic Energy Community - EURATOM Reprinted from „Nature", Vol. 197, No. 4808 - 1963, pages 648-649. Summary not available. E U R 3 1 1 . e REPRINT EVIDENCE THAT THE Xg BLOOD GROUP GENES ARE ON THE SLIORT ARM OF THE X CHROMOSOMES by M. FRACCARO, J.L. HAMERTOX, J. LINDSTEN, P.E. POLANI, R.R. RACE and R. SANGER. European Atomic Energy Community - EURATOM Reprinted from „Nature", Vol. 197, No. 4868 - 1963, pages 648-649. Summary not available. (Reprinted from Nature, Vol. 197, No. 4868, pp. 648-649, February 16, 1963) EVIDENCE THAT THE Xg BLOOD GROUP GENES ARE ON THE SHORT ARM OF THE X CHROMOSOME By J. LINDSTEN Department of Endocrinology and Metabolism, Karolinska Sjukhuset, Stockholm 60 DR. M. FRACCARO Biology Division, Euratom, c/o Istituto di Genetica, Università di Pavia PROF. P. E. POLANI and J. L. HAMERTON Paediatric Research Unit, Guy's Hospital Medical School, London, S.E.I AND ' DR. RUTH SANGER and DR. R. R. RACE, F.R.S. Medical Research Council Blood Group Research Unit, Lister Institute, London, S.W.I FROM an examination of two women with ovarian dysgenesis, and. of their families, evidence has emerged which suggests that the locus for Xg, the X-linked blood group system1, is on the short arm of the X chromosome. The two patients were consistently sex chromatin positive and each displayed, in the tissues sampled for cytologicai study, chromosome mosaicism of two cell lines : one, the minority, had 45 chromosomes including a single, X and the other, the majority, had 46 chromosomes. In the cells of the latter line there was one normal X chromo-some and a metacentric chromosome resembling No. 3 of the set; this abnormal chromosome has been interpreted2, in these and in other patients with similar karyotype, as an isochromosome for the long arm of the X chromosome. While other interpretations are possible the suggestion that these metacentric chromosomes are isochromosomes for the long arm of the X seems likely from the combined cytological and clinical evidence. A recent observation3 supports this interpretation: the sex chromatin masses of five such patients have a greater amount of DNA than do those of normal females. Furthermore, the presump-tive isochromosomes have been shown1·6 to be symmetri-cally 'hot' along their whole length when labelled with 3H-thymidine late in the period of DNA synthesis. The argument to follow concerning the site of the Xg locus hinges on this interpretation—that the structurally altered chromosome consists of two long arms of the X chromosome without a short arm. Family J. The pedigree of this family is shown in Fig. 1. The proposita, I I I-3, briefly reported by Lindsten0, is aged eighteen ; she has primary amenorrhoea and the out-put of pituitary gonadotrophin in her tirine is increased while that of œstrogens is decreased. She is of short stature (4 ft. 6 in. or 138 cm). She has neither an unusual number of pigmented nævi nor webbing of the neck. Her father was thirty-three and her mother twenty-five at the time of her birth. Cytological investigations showed that the proposita was sex chromatin positive in cells from buccal mucosa smears, skin sections and in colls from two skin biopsies grown in vitro. Cells were cultured from one blood sample and from two different skin biopsies and chromo -somo mosaicism was observed: the majority of cells had 46 chromosomes including an apparently normal X and a presumptive isochromosome for the long arm of the X, the minority of cells had 45 chromosomes with an XO karyo-type. The parents and sibs of the proposita have sex chromatin corresponding to their phenotypic sex. From the family history it is clear that the maternal grandfather, 1-2, was colour blind. By Ishihara and anomaloscope tests III-2 and III-5 are deuteranopic : the proposita, III-3, is deuteranopic according to Ishihara but has a normal Raleigh equation with an increased contrast. By both tests II-3 and II-4 and III-1-4-6 were normal, and by Ishihara II-1 and II-2 were normal. The Xg groups of the family are shown in the pedigree. The proposita lacks her father's Xga antigen and this indicates that her normal X is from her mother, as does the fact that she has her mother's colour -blindness gene but not her father's gene for normal colour vision: the iso-chromosome would therefore have to be of paternal origin. (The family illustrates crossing-over between the loci for Xg and for deutan colour vision; this is to be expected for the cross-over rate between the two genes is known to be high7.) Family R. The pedigree of this family is shown in Fig. 1. The proposita, II-2, is aged twenty-two years, has primary amenorrhoea with markedly increased output of pituitary gonadotrophin, is of short stature (4 ft. 9¿ in. or 146 cm) and has numerous pigmented nævi but no webbing of the neck. At the time of her birth her father was thirty-one and her mother twenty-six. She has a normal elder brother. The patient is sex chromatin positive in cells from the oral mucosa, from skin biopsy grown in vitro and in the leucocytes of the blood smear ; some of the sex chromatin masses in the oral mucosa cells appeared to be unusually largo. The patient's chromosomes Avere examined in cells from two blood cultures and one skin culture and showed her to be a chromosome mosaic : the majority of her cells had 46 chromosomes, including an apparently normal X I o­d. π I ­HJ </. I o-4­~& 4­I Õ' É · 5 O' É + ­Ι­ ο', d. Fig. 1. The family J. (left) and the family E. (right). Arrow = proposita. Xg groups: + = Xg(a­f), ­ = Xg(a — ). Colour vision: solid black = colour­blind (deuteranopic), hollow = normal (for details see text), d. = dead and not tested for Xg or for colour vision and a presumptive isochromosomo for the long arm of the X, and the minority of cells had 45 chromosomos with an XO karyotypo. The presumptive isochromosome in the cells with 46 cliromosomes was found5 to be symmetrically 'hot' and to label with 3H­thymidino lator than tho other chromosomes in the courso of DNA synthosis. Tho fathor and mother had a normal chromosome complomont in colls from blood cultures. The proposita, her mother and fathor have normal colour vision; the first two wore tostod on tho anomalo­scope and tho Ishihara, the fathor only on tho lattor. The Xg groups of the family aro shown in tho pedigroe : bocauso tho proposita is Xg(a — ) while hor fathor is Xg(a + ) it must be considered that the morphologically normal X which she has in both her coll lines is from hor mother (who must be heterozygous XgnXg). I t follows that, tho presumptive isochromosomo present in tho colls with 46 chromosomos is of patornal origin—j'ot tho patient is Xg(a — ). Other cases. The families of 12 other pationts who have presumptive isochromosomes for tho long arm of tho X have been tested, but tho Xg groups did not segregato in the informativo way thoy did in tho J. and R. familios. The groups of those other familios are recorded in Table 1 : in four of the 12 patients tho presumptive isochromosomo appears to be of paternal origin (families Fra., AIL, And., Eri.; see discussion). Discussion. Analysis of tho two familios, J. and R., indicates that the presumptive isochromosome of both patients is of paternal origin. If this abnormal chromo­some found in tho Xg(a — ) daughters consists of two long arms of the X chromosomo from the Xg(a + ) father thon these arms do not contain the Xg locus, which should therefore be located on the short arm. (Tho ovidonco that family J. gives for the deutan locus being on the short arm has already been discussed8,9.) lì T a b l e l . T W E L V E F A M I L I E S I N W H I C H I H E P R O P O S I T A H A S A P R E S U M P T I V E ISOCHROHOSOME FOR THE LONG ARM OP THE X BUT IN WHICH THE X g GROUPS ARE LESS INFORMATIVE THAN THOSE OF THE FAMILIES J . AND R. Investigator Court Brown and Whyte Motulsky Polani and Hamerton Lindsten Identi-fication Hig." Tho.* Sea. Fra. Gib.* Rog. Las.* AH.* And. Eri. Sjo. Sve. Father + + c.b. + + + + Mother + + + + + + + t + + + + + Xg groups of Proposita Brothers + + c.b. + + + + + + + + -+ + + + + + Siste + + + + + + ,Xg(a + ). — ,Xg(a —). c.b., colour blind. * not found to be a mosaic (XO/X iso-X). t Her mother, sister and 2 brothers are all + . Two possibilities could upset this argument. The hypothesis of Lyon10, which postulates that in the mouse and possibly in all mammals only one X chromosome is 'active' in any one cell, makes it theoretically possible that the isochromosomes of our two patients are 'inactive' in all cells. If this were so the Xg(a — ) reactions of the two patients could merely reflect lack of gene action and would not afford evidence of the arm on which Xg is located. The fact that the isochromosome is 'hot' when labelled with 3H-thymidine late in the period of DNA synthesis4·5 indicates that it synthesizes later than the other chromo-somes: whether this means that it is also 'inactive' remains to be demonstrated. The second possibility is that the two different cell lines found in both patients might be so distributed that those producing the Xg groups have 45 chromosomes including the single, maternal, X carrying the silent Xg gene. In this event again the Xg locus could be on either arm of the X chromosome. However, an identical, non-random dis-tribution of two cell lines in two unrelated individuals seems most unlikely. Thus, though the evidence is suggestive, definite proof that the Xg locus is on the short arm of the X chromosome must await clarification of these problems. In some of the patients, the Xg findings can help in tracing the origin of the presumptive isochromosomes, but there are certain limitations and two sets of factors have to be taken into consideration: the 'activity' or otherwise of the presumptive isochromosomes and the situation of the Xg locus on the short or long arm of X chromosomes generally. If the presumptive isochromo-somes of the patients were 'inactive' in all oells, a paternal origin could be assumed in six of the 14 patients (R., J., Fra., All., And., Eri.) irrespective of the situation of the Xg locus: on the other hand, if they were 'active', one could conclude a paternal origin for the six only on the assumption that the Xg locus is on the short arm. In the two patients J. and R., 'activity' of the isochromosomes would imply that the Xg locus is on the short arm (if we disregard mosaicism), and indeed this is the object of the present article. We thank Dr. P. M. F . Bishop, London, who referred the proposita of family R. for investigation, Dr. M. Svenmar, Rävemåla, for help in obtaining blood samples from the family J., and Prof. I. Kugelberg, Stockholm, for the colour vision investigation of that family. We also thank Dr. W. M. Court Brown, Edinburgh, Dr. E. G. Oastler and Dr. W. G. Whyte, Glasgow, and Dr. A. Motulsky, Seattle, for samples from three of tho familios listed in Table 1. We thank Dr. J . D.Mann, Grand Rapids, and Dr. A. Cahan, Now York, for generous supplies of the anti­Xga serum. One of us (J. L.) gratefully acknowledges a grant from Nordisk Insulinfond. 1 Mann, ,T. D., Cahan, Α., Gelb, Α. G., Fisher. Ν., Hamper, J., Tippelt, P., Sauger, It., and Race, R. TL., Lancet, i, 8 (1902). 'Fraecaro, M., Ikkos, D., Lindsten, J., Luft, lt., and Kaijser, Κ., Lancet, ii, 1144 (I960). 3 Klinger, H. P., Lindsten, J., and Fraecaro, M. (in preparation). 'Muldal, S., Gilbert, C. W., Lajtha, L. G., Lindsten, J., Rowley, J., and Fraecaro, M. (in preparation). 5 Giannelli, F. (in preparation). • Lindsten, J., Lancet, i, 1228 (19G1). ' Jackson, C. E., Symon, W. E., and Mann, J. D., Lancet, ii, 512 (1902). 8 Stewart, J. S. S. Lancet, ii, 104 (1961). ' Polani, P. E., and Hamerton, J . L., Lancet, ii, 202 (1901). '" Lyon, M. F., Nature. 190, 372 (1901). Printed in Great Britain by Fisher, Knight & Co.. Ltd., St. Albans. 

EVIDENCE THAT THE Xg BLOOD GROUP GENES ARE ON THE SHORT ARM OF THE X CHROMOSOME. EUR 311.e

ί|!Ρ^!^^» 
GROUP GENES ARE ON THE SHORT ARM 
E G A L NOTICE 
This document was prepared under the sponsorship of the Commission of the European 
Atomic Energy Community (EURATOM). 
W 
ÄÄfiiii?» 
Neither the Eura tom Commission, its contractors nor any person acting on their behalf : 
Make any warran ty or representation, express or implied, with respect to the accuracy, 
completeness, or usefulness of the information contained in this document, or t ha t the use 
of any information, apparatus , method, or process disclosed in this document may not 
infringe privately owned r ights ; or m - ■ % " ■ ■ 
— Assume any liability with respect to the use of, or for damages resulting from the use of 
any information, apparatus , method or process disclosed in this document. 
The authors;' aansar asm Beted 
arm 
The authors' names are listed 
in alphabetical order 
This reprint is intended for restricted distribution only. It reproduces, 
by hind permission of the publisher, an article from ,,NATURE", 
Vol. 197, No. 4868 ­ 1963, 648­649. For further copies please apply 
to Fisher, Knight & Co., Ltd, Gainsborough Press, Lattimore Road —■ 
St. Albans, Hertfordshire (England). 
Dieser Sonderdruck ist für eine beschränkte Verteilung bestimmt. Die 
Wiedergabe des vorliegenden in „NATURE", Vol. 197, Nr. 4868 ­
1963, 648­649 erschienenen Aufsatzes erfolgt mit freundlicher Geneh­
migung des Herausgebers. Bestellungen weiterer Exemplare sind an 
Fisher, Knight & Co., Ltd., Gainsborough Press, Lattimore Road — 
St. Albans, Hertfordshire (England), zu richten. 
Ce tiré­à­part est exclusivement destine à une diffusion restreinte. Il 
reprend, avec l'aimable autorisation de l'éditeur, un article publié dans 
« NATURE », Vol. 197, N° 4868 ­ 1963, 648­649. Tout autre exem­
plaire de cet article doit être demandé à Fisher, Knight & Co., Ltd., 
Gainsborough Press, Lattimore Road — St. Albans, Hertfordshire 
(England). !'>'H ' ^ i 
m 
ìtfi 
­m irou 
3' 
Questo estratto è destinato esclusivamente ad una diffusione limitata. 
Esso è stato riprodotto, per gentile concessione dell'Editore, da 
« NATURE », Voi. 197, N° 4868 ­ 1963, 648­649. Ulteriori copie 
dell'articolo debbono essere richieste a Fisher, Knight & Co., Ltd., 
Gainsborough Press, Lattimore Road — St. Albans, Hertfordshire 
(England). Süfi^ PI S H I 
Deze overdruk is slechts voor beperkte verspreiding bestemd. Het artikel 
is. met ­welwillende toestemming van de uitgever overgenomen uit 
„NATURE", Vol. 197, No. 4868 ­ 1963, 648­649. Meer exemplaren 
kunnen besteld worden bij Fisher, Knight & Co., Ltd., Gainsborough 
Press, Lattimore Road — St. Albans, Hertfordshire (England). 
yjHitJ^tft \ 
E U R 3 1 1 . e 
REPRINT 
EVIDENCE THAT THE Xg BLOOD GROUP GENES ARE ON THE SHORT 
ARM OF THE X CHROMOSOMES by M. FRACCARO. J.L. HAMERTOX, 
J. LINDSTEN, P.E. POLANI, R.R. RACE and R. SANGER. 
European Atomic Energy Community - EURATOM 
Reprinted from „Nature", Vol. 197, No. 4868 - 1903, pages 648-1549. 
Summary not available. 
E U R 3 1 1 . e 
REPRINT 
EVIDENCE THAT THE Xg BLOOD GROUP GENES ARE ON THE SHORT 
ARM OF THE X CHROMOSOMES by M. FRACCARO, J.L. HAMERTOX, 
J. LINDSTEN, P.E. POLANI, R.R. RACE and R. SANGER. 
European Atomic Energy Community - EURATOM 
Reprinted from „Nature", Vol. 197, No. 4808 - 1963, pages 648-649. 
Summary not available. 
E U R 3 1 1 . e 
REPRINT 
EVIDENCE THAT THE Xg BLOOD GROUP GENES ARE ON THE SLIORT 
ARM OF THE X CHROMOSOMES by M. FRACCARO, J.L. HAMERTOX, 
J. LINDSTEN, P.E. POLANI, R.R. RACE and R. SANGER. 
European Atomic Energy Community - EURATOM 
Reprinted from „Nature", Vol. 197, No. 4868 - 1963, pages 648-649. 
Summary not available. 

(Reprinted from Nature, Vol. 197, No. 4868, pp. 648-649, 
February 16, 1963) 
EVIDENCE THAT THE Xg BLOOD 
GROUP GENES ARE ON THE SHORT 
ARM OF THE X CHROMOSOME 
By J. LINDSTEN 
Department of Endocrinology and Metabolism, Karolinska 
Sjukhuset, Stockholm 60 
DR. M. FRACCARO 
Biology Division, Euratom, c/o Istituto di Genetica, 
Università di Pavia 
PROF. P. E. POLANI and J. L. HAMERTON 
Paediatric Research Unit, Guy's Hospital Medical School, 
London, S.E.I 
AND 
' DR. RUTH SANGER and DR. R. R. RACE, F.R.S. 
Medical Research Council Blood Group Research Unit, 
Lister Institute, London, S.W.I 
FROM an examination of two women with ovarian dysgenesis, and. of their families, evidence has 
emerged which suggests that the locus for Xg, the 
X-linked blood group system1, is on the short arm of the 
X chromosome. 
The two patients were consistently sex chromatin 
positive and each displayed, in the tissues sampled for 
cytologicai study, chromosome mosaicism of two cell lines : 
one, the minority, had 45 chromosomes including a single, 
X and the other, the majority, had 46 chromosomes. In 
the cells of the latter line there was one normal X chromo-
some and a metacentric chromosome resembling No. 3 of 
the set; this abnormal chromosome has been interpreted2, 
in these and in other patients with similar karyotype, as 
an isochromosome for the long arm of the X chromosome. 
While other interpretations are possible the suggestion 
that these metacentric chromosomes are isochromosomes 
for the long arm of the X seems likely from the combined 
cytological and clinical evidence. A recent observation3 
supports this interpretation: the sex chromatin masses 
of five such patients have a greater amount of DNA than 
do those of normal females. Furthermore, the presump-
tive isochromosomes have been shown1·6 to be symmetri-
cally 'hot' along their whole length when labelled with 
3H-thymidine late in the period of DNA synthesis. 
The argument to follow concerning the site of the Xg 
locus hinges on this interpretation—that the structurally 
altered chromosome consists of two long arms of the X 
chromosome without a short arm. 
Family J. The pedigree of this family is shown in Fig. 
1. The proposita, I I I-3, briefly reported by Lindsten0, is 
aged eighteen ; she has primary amenorrhoea and the out-
put of pituitary gonadotrophin in her tirine is increased 
while that of œstrogens is decreased. She is of short 
stature (4 ft. 6 in. or 138 cm). She has neither an unusual 
number of pigmented nævi nor webbing of the neck. Her 
father was thirty-three and her mother twenty-five at the 
time of her birth. 
Cytological investigations showed that the proposita 
was sex chromatin positive in cells from buccal mucosa 
smears, skin sections and in colls from two skin biopsies 
grown in vitro. Cells were cultured from one blood 
sample and from two different skin biopsies and chromo -
somo mosaicism was observed: the majority of cells had 
46 chromosomes including an apparently normal X and a 
presumptive isochromosome for the long arm of the X, the 
minority of cells had 45 chromosomes with an XO karyo-
type. The parents and sibs of the proposita have sex 
chromatin corresponding to their phenotypic sex. 
From the family history it is clear that the maternal 
grandfather, 1-2, was colour blind. By Ishihara and 
anomaloscope tests III-2 and III-5 are deuteranopic : the 
proposita, III-3, is deuteranopic according to Ishihara 
but has a normal Raleigh equation with an increased 
contrast. By both tests II-3 and II-4 and III-1-4-6 were 
normal, and by Ishihara II-1 and II-2 were normal. 
The Xg groups of the family are shown in the pedigree. 
The proposita lacks her father's Xga antigen and this 
indicates that her normal X is from her mother, as does the 
fact that she has her mother's colour -blindness gene but 
not her father's gene for normal colour vision: the iso-
chromosome would therefore have to be of paternal 
origin. (The family illustrates crossing-over between the 
loci for Xg and for deutan colour vision; this is to be 
expected for the cross-over rate between the two genes is 
known to be high7.) 
Family R. The pedigree of this family is shown in Fig. 1. 
The proposita, II-2, is aged twenty-two years, has primary 
amenorrhoea with markedly increased output of pituitary 
gonadotrophin, is of short stature (4 ft. 9¿ in. or 146 cm) 
and has numerous pigmented nævi but no webbing of the 
neck. At the time of her birth her father was thirty-one 
and her mother twenty-six. She has a normal elder 
brother. 
The patient is sex chromatin positive in cells from the 
oral mucosa, from skin biopsy grown in vitro and in the 
leucocytes of the blood smear ; some of the sex chromatin 
masses in the oral mucosa cells appeared to be unusually 
largo. The patient's chromosomes Avere examined in cells 
from two blood cultures and one skin culture and showed 
her to be a chromosome mosaic : the majority of her cells 
had 46 chromosomes, including an apparently normal X 
I o­
d. 
π 
I ­HJ 
</. 
I o-
4­
~& 
4­
I Õ' 
É · 5 O' É 
+ ­Ι­ ο', d. Fig. 1. The family J. (left) and the family E. (right). Arrow = proposita. Xg groups: + = Xg(a­f), ­ = Xg(a — ). Colour vision: solid black = colour­blind (deuteranopic), hollow = normal (for details see text), d. = dead and not tested for Xg or for colour vision 
and a presumptive isochromosomo for the long arm of the 
X, and the minority of cells had 45 chromosomos with an 
XO karyotypo. The presumptive isochromosome in the 
cells with 46 cliromosomes was found5 to be symmetrically 
'hot' and to label with 3H­thymidino lator than tho other 
chromosomes in the courso of DNA synthosis. Tho fathor 
and mother had a normal chromosome complomont in colls 
from blood cultures. 
The proposita, her mother and fathor have normal 
colour vision; the first two wore tostod on tho anomalo­
scope and tho Ishihara, the fathor only on tho lattor. 
The Xg groups of the family aro shown in tho pedigroe : 
bocauso tho proposita is Xg(a — ) while hor fathor is 
Xg(a + ) it must be considered that the morphologically 
normal X which she has in both her coll lines is from hor 
mother (who must be heterozygous XgnXg). I t follows 
that, tho presumptive isochromosomo present in tho colls 
with 46 chromosomos is of patornal origin—j'ot tho 
patient is Xg(a — ). 
Other cases. The families of 12 other pationts who have 
presumptive isochromosomes for tho long arm of tho X 
have been tested, but tho Xg groups did not segregato in 
the informativo way thoy did in tho J. and R. familios. 
The groups of those other familios are recorded in Table 1 : 
in four of the 12 patients tho presumptive isochromosomo 
appears to be of paternal origin (families Fra., AIL, And., 
Eri.; see discussion). 
Discussion. Analysis of tho two familios, J. and R., 
indicates that the presumptive isochromosome of both 
patients is of paternal origin. If this abnormal chromo­
some found in tho Xg(a — ) daughters consists of two long 
arms of the X chromosomo from the Xg(a + ) father thon 
these arms do not contain the Xg locus, which should 
therefore be located on the short arm. (Tho ovidonco that 
family J. gives for the deutan locus being on the short 
arm has already been discussed8,9.) 
lì 
T a b l e l . T W E L V E F A M I L I E S I N W H I C H I H E P R O P O S I T A H A S A P R E S U M P T I V E 
ISOCHROHOSOME FOR THE LONG ARM OP THE X BUT IN WHICH THE X g 
GROUPS ARE LESS INFORMATIVE THAN THOSE OF THE FAMILIES J . AND R. 
Investigator 
Court Brown 
and Whyte 
Motulsky 
Polani and 
Hamerton 
Lindsten 
Identi-
fication 
Hig." 
Tho.* 
Sea. 
Fra. 
Gib.* 
Rog. 
Las.* 
AH.* 
And. 
Eri. 
Sjo. 
Sve. 
Father 
+ 
+ c.b. 
+ 
+ 
+ 
+ 
Mother 
+ 
+ 
+ 
+ 
+ 
+ 
+ t 
+ 
+ 
+ 
+ 
+ 
Xg groups of 
Proposita Brothers 
+ 
+ c.b. 
+ 
+ 
+ 
+ 
+ 
+ 
+ 
+ 
-
+ 
+ + + 
+ + 
Siste 
+ 
+ 
+ 
+ 
+ 
+ ,Xg(a + ). — ,Xg(a —). c.b., colour blind. 
* not found to be a mosaic (XO/X iso-X). 
t Her mother, sister and 2 brothers are all + . 
Two possibilities could upset this argument. The 
hypothesis of Lyon10, which postulates that in the mouse 
and possibly in all mammals only one X chromosome is 
'active' in any one cell, makes it theoretically possible that 
the isochromosomes of our two patients are 'inactive' in 
all cells. If this were so the Xg(a — ) reactions of the two 
patients could merely reflect lack of gene action and would 
not afford evidence of the arm on which Xg is located. The 
fact that the isochromosome is 'hot' when labelled with 
3H-thymidine late in the period of DNA synthesis4·5 
indicates that it synthesizes later than the other chromo-
somes: whether this means that it is also 'inactive' 
remains to be demonstrated. 
The second possibility is that the two different cell lines 
found in both patients might be so distributed that those 
producing the Xg groups have 45 chromosomes including 
the single, maternal, X carrying the silent Xg gene. In 
this event again the Xg locus could be on either arm of the 
X chromosome. However, an identical, non-random dis-
tribution of two cell lines in two unrelated individuals 
seems most unlikely. 
Thus, though the evidence is suggestive, definite proof 
that the Xg locus is on the short arm of the X chromosome 
must await clarification of these problems. 
In some of the patients, the Xg findings can help in 
tracing the origin of the presumptive isochromosomes, 
but there are certain limitations and two sets of factors 
have to be taken into consideration: the 'activity' or 
otherwise of the presumptive isochromosomes and the 
situation of the Xg locus on the short or long arm of X 
chromosomes generally. If the presumptive isochromo-
somes of the patients were 'inactive' in all oells, a paternal 
origin could be assumed in six of the 14 patients (R., J., 
Fra., All., And., Eri.) irrespective of the situation of the 
Xg locus: on the other hand, if they were 'active', one 
could conclude a paternal origin for the six only on the 
assumption that the Xg locus is on the short arm. In the 
two patients J. and R., 'activity' of the isochromosomes 
would imply that the Xg locus is on the short arm (if we 
disregard mosaicism), and indeed this is the object of the 
present article. 
We thank Dr. P. M. F . Bishop, London, who referred 
the proposita of family R. for investigation, Dr. M. 
Svenmar, Rävemåla, for help in obtaining blood samples 
from the family J., and Prof. I. Kugelberg, Stockholm, 
for the colour vision investigation of that family. We also 
thank Dr. W. M. Court Brown, Edinburgh, Dr. E. G. 
Oastler and Dr. W. G. Whyte, Glasgow, and Dr. A. 
Motulsky, Seattle, for samples from three of tho familios 
listed in Table 1. We thank Dr. J . D.Mann, Grand Rapids, 
and Dr. A. Cahan, Now York, for generous supplies of the 
anti­Xga serum. 
One of us (J. L.) gratefully acknowledges a grant from 
Nordisk Insulinfond. 
1 Mann, ,T. D., Cahan, Α., Gelb, Α. G., Fisher. Ν., Hamper, J., Tippelt, P., 
Sauger, It., and Race, R. TL., Lancet, i, 8 (1902). 
'Fraecaro, M., Ikkos, D., Lindsten, J., Luft, lt., and Kaijser, Κ., Lancet, 
ii, 1144 (I960). 
3 Klinger, H. P., Lindsten, J., and Fraecaro, M. (in preparation). 
'Muldal, S., Gilbert, C. W., Lajtha, L. G., Lindsten, J., Rowley, J., and 
Fraecaro, M. (in preparation). 
5 Giannelli, F. (in preparation). 
• Lindsten, J., Lancet, i, 1228 (19G1). 
' Jackson, C. E., Symon, W. E., and Mann, J. D., Lancet, ii, 512 (1902). 
8 Stewart, J. S. S. Lancet, ii, 104 (1961). 
' Polani, P. E., and Hamerton, J . L., Lancet, ii, 202 (1901). 
'" Lyon, M. F., Nature. 190, 372 (1901). 
Printed in Great Britain by Fisher, Knight & Co.. Ltd., St. Albans. 







EVIDENCE THAT THE Xg BLOOD GROUP GENES ARE ON THE SHORT ARM OF THE X CHROMOSOME. EUR 311.e

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