Humangenetik 11, 78--80 (1970) © by Springer-Verlag 1970

Localization Exclusion of the HL-A Genes from the Short Arm of Human Chromosome 5

K. BENDEI%*

Institut fiir Humangenetik der Universit~t Freiburg i. Br.

F. SCHINDEI~A

Kindcrklinik der Universit~t Freiburg i. Br.

F. K IS SMEYEI~-I~IELSEN * *

Blood Bank and Blood Grouping Laboratory, The University Hospital, Arhus, Denmark

Received September 9, 1970

Summary. A cri du chat patient with deletion of more than a/4 of the short arm of one chromosome 5 was found to be heterozygous at both of the closely linked ttL-A gene loci, thus demonstrating that the HL-A genes cannot be located on the missing segment.

Zusammen]assung. Bei einem Patienten mit Cri du chat-Syndrom und einer Chromosomcn- defizienz, die mehr als 3~ des kurzen Armes eines Chromosoms 5 umfaBt, wurdc Hcterozygotie an beiden der enggekoppelten HL-A-Gene festgestellt. Damit kSnnen die HL-A-Gene nicht auf dem deletierten Absehnitt Iokalisicrt scin.

Dele t ions on the shor t a rm of a chromosome 5 occur wi th a f requency of a b o u t 1 in 50,000 to 100,000 newborns (Polani, 1969). The deficiency is associa ted wi th a well-defined clinical ma l fo rma t ion syndrome, known as the eri du cha t synd rome (Lejeune et al., 1963). F r o m a t leas t 26 eri du cha t pa t i en t s wi th de t ec t ab le dele- t ions gene mapp ing s tudies have been repor ted . Only one ass ignment was discussed, t h a t of the gene locus coding for the enzyme tr iose phospha te i somerase (Sparkes et al., 1969), b u t was no t s u p p o r t e d b y the f indings of o ther au thor s (Rfidiger et al., ci ted f rom Passarge , 1970; Brock and Singer, 1970). The genes of most of the known b lood group markers , se rum pro te ins and a n u m b e r of enzymes could be exc luded f rom being local ized on the missing segment (Bender and B u r c k h a r d t , 1970). No d a t a have been r epo r t ed so far on the I I L - A t r a n s p l a n t a t i o n sys tem in connect ion wi th h u m a n chromosome mapping . The recent f inding b y us of a pa t i e n t missing more t h a n 3~ of the shor t a r m of a chromosome 5 led us to s t u d y the p h e n o t y p e for th is new genet ic m a r k e r sys tem.

The p a t i e n t (U. N. , Un ive r s i t / i t s -Kinderk l in ik Fre iburg , Nr . 41.11959.2; Ins t i - r u t fiir t I u m a n g e n e t i k Fre iburg , Nr. C 2602) is a 6 mon ths -o ld -boy wi th t yp i ca l fea tures of the eri du cha t syndrome. Bo th pa ren t s are h e a l t h y and have norma l k a r y o t y p e s .

* Supported by the Deutsche Forschungsgemeinschaft. ** Supported by The Danish State Research Foundation and Einar Willumsen's Foundation.

Localization Exclusion of the HL-A Genes from the Short Arm of Chromosome 5 79

Table 1. HL-A tissue antigens o/the child determined with lymphocytotoxic antibodies

LA-locus Four-locus

- - + ~ - - ÷ ÷

Phenotype : HL-A 2, 3, 7, LND.

Table 2. Blood g~'oups and serum types o/the child and parents

Child Mother Father

A1 A1 A1 MN N MN SS SS SS

k k k CCD.ee C w - CCD.ee C w - CCI).ee C w - Fy(a ) (a--) (a--) Hp i--I 1 1 2--i Gc 2 1 2--1 1--1 Gm(--~) (--~) (--1) Inv(--1) ( t) (--1) Tf CC CC CC ac.P. AB BB BB PGM 1 1--1 1--1 1--1 PGM 2 1--1 1--1 1--1 AK 1--1 1 1 1--1 ADA 1 1 1 1 1 1 6-PGD AA AA AA LDH AABB AABB AABB

The results of the H L - A typ ing are g iven in Table 1. F r o m this i t can be seen

t h a t the child is he terozygous a t bo th of the closely l inked genes of this system,

namely the LA and the F O U R gone locus. Consequent ly , the H L - A genes cannot

be loca ted on the missing chromosome segment . Fo r a deta i led descr ipt ion of thc

H L - A sys tem see Kissmeyer-Nie lsen and Thorsby (1970).

I n Table 2 the blood groups and serum proteins of the child and parents are

presented. The da ta confirm the local izat ion exclusion of the genes for MN, Gc,

and acid phosphatase . No ass ignment could be der ived by compar ing the child 's

wi th the paren t ' s phenotype .

References

Bonder, K., Burckhardt, K. : On the localization of genes on certain autosomes of man through chromosome aberrations. III. Exclusion of the possibility of gone assignment. Human- genetik 9, 75--85 (1970).

Brock, D. J. H., Singer, J. D. : Rod cell trioscphosphate isomerase and chromosome 5. Lancet 1 9 7 0 I I , 4 5 - - 4 6 .

80 Bender, Schindera, and Kissmeyer-Nielsen: Localization Exclusion of the HL-A Genes

Kissmeyer-Nielsen, F., Thorsby, E.: Human transplantation antigens. Appendix: Current methods in histocompatibility testing. Transplant. l~ev. 4, 1--176 (1970).

Lejeune, J., Lafourcade, J., Berger, 1~., Vialette, J., Boeswillwald, M., Seringe, P., Turpin, R. : Trois cas de deletion partielle du bras court d'nn chromosome 5. C. R. Acad. Sci. (Paris) 257, 3098--3102 (1963).

Passarge, E. : Population cytogenetics, assignment of gene loci to autosomes, karyotype- phenotype correlations. A progress report on human cytogenetics. Humangenetik 9, 1--15 (1970).

Polani, P. E. : Autosoma] imbalance and its syndromes, excluding Down's. Brit. reed. Bull. 25, 81--93 (1969).

Sparkes, i~. S., Carrel, I~. E., Paglia, D. E. : Probable localization of a triosephosphate isomerase gene to the short arm of the number 5 human chromosome. Nature (Lond.) 224, 367--368 (1969).

I)r. Klaus ~Bender Institut ffir I-Iumangenetik und Anthropologie der Universiti~t D-7800 Freiburg i. Br., Albertstra~e 11