232 BRIEF REPORTS Hereditas 84 (1976)

GARSON, 0. M. and MILLIGAN, W. J . 1974. Acute leukaemia associated with an abnormal genotype. - Scand. J . Haema-

LAWLER, S . D.. SECKER WALKER, L. M.. SUMMERSGILL, B. M., REEVES, B. R.. LEWIS, J., KAY, H. E. M. and HARDISTY, R. M. 1975. Chromosome banding studies in acute leukaemia at diagnosis. - Scand. J . Haematol. I S : 312-320

MCCAFFREY, R., HARRISON, T. A,, PARKMAN, R. and BALTI- MORE. D. 1975. Terminal deoxynucleotidyl transferase activi- ty in human leukemic cells and in normal human thymo- cytes. - New Engl. J . Med. 292: 775-780

SCHMIDT, R., DAR, H. and NITOWSKY, H. M. 1974. Cyto- genetic studies in myeloproliferative disorders. - Am. J . Hum. Genet. 26: 77 A

to/. 12: 256-262

SCHMIDT, R., DAR, H. , SANTORINEOU, M. and SEKINE, I. 1975. Ph’ chromosome and loss and reappearance of the Y chromo- some in acute lymphocytic leukaemia. -- Lunret ( I ) : I145

SECKER WALKER, L. M. and HARDY, J . D. 1975. Philadelphia chromosome in P.H.A. stimulated lymphocytes in acute leukaemia. - Lancer (2): 1301--1302

Preben Philip Division of Haematology. Departmed of Medicine A Rigshospitalet Blegdamsvej 9 DK-2100 Copenhagen 0. Denmark

E. ANDRESEN and P. WILLEBERG: Pituitary dwarfism in Carelian Bear-Dogs: Evidence of simple, autosomal recessive inheritance (Received September 14, 1976)

Dwarfism due to congenital pituitary malformation has been observed among dogs of the German Sherpherd breed (ANDRESEN et al. 1974). Somato- medin analyses gave low values indicating impaired growth-hormone production to be involved (WILLE- BERG et al. 1975). The pedigree and the segregation results supported a hypothesis of simple, autosomal recessive inheritance (ANDRESEN and WILLEBERG 1976). In the present report the evidence indicates a similar mode of inheritance for pituitary dwarfism detected among Carelian Bear-Dogs. Moreover, the breed history suggests a common origin of the “dwarfing gene” in the two breeds.

The animal material includes nine dwarfs (6 females and 3 males) belonging to six litters born during the period July 1968-May 19757Fig. 1). All cases appeared spontaneously in the population of Carelian Bear-Dogs registered by Danish Kennel Club. The litters and their parents were ascertained through the respective dwarfs. Information about ancestors was obtained from the registration books provided by the owners and Danish Kennel Club.

The two female dwarfs depicted in Fig. 2 corre- spond to F and G in Fig. 1. They both have to be regarded as probands because they were the first dwarfs to be observed and they were reported simultaneously. In addition to the proband litters four litters have been detected, each with one or two dwarfs. The four litters contain a total of 34 indi- viduals, including seven dwarfs, 23 phenotypically normal dogs, one stillborn female (V-33), and three dogs who died prior to possible diagnosis of dwarf-

ism. According to available information the two male dwarfs B and E were disposed of and the male dwarf I was accidentally killed prior to this investiga- tion.

The probands were 16 and 8 months old, respec- tively, when they were first reported (February 1976). They were approximately 30 cm high, measured at the shoulder region and they weighed 7; and 5 kg, respectively. When the four females A, C, D, and H were approximately 7;, 4$, 4;. and 1; years of age they were 30-35 cm high; their weights were not recorded. The height of adult, normal females of this breed is 48-53 cm and the weight is 25-30 kg. The dwarfs F, G, and H had retained the puppy hair coat, whereas A, C, and D possessed normally appearing adult hair coat. However, according to the owners’ information which was confirmed by photo- graphs these three dogs almost had lost their entire hair coat during a period when they were between 2 and 3 years of age. Inspection and palpation of the bones indicated normal form and proportions. Low somatomedin values for the probands support the diagnosis of pituitary dwarfism (WILLEBERG et al. 1975). However, so far a Carelian Bear-Dog dwarf has not been available for necropsy. Thus, a patho- logical-anatomical comparison with pituitary dwarf- ism in German Shepherd dogs is not yet possible.

The proband litters were not included in the statistical test summarized in Table 1. This test is based on a correction of a 3:l a priori expectation, see e.g. ANDRESEN (1974). The observed ratio of 23 normal : 7 affected dogs is in good agreement

BRIEF REPORTS 233 Herediras 84 ( I 976)

I

II

111

IV

V

0 0 1 3

1 2 3 4 5 6 7

I

Fig. I. Pedigree for nine Carelian Bear-Dog dwarfs, two of which. F and G, are the probands. No. V-33 was a stillborn female and nos. V-I I , V-14, and V-I5 died before diagnosis of dwarfism was possible.

with the expected ratio of 21.5: 8.5, the probability value being 0.50 < P <0.70.

Referring to Fig. 1 it should be noticed that the individuals 1-1 and 1-2 are common ancestors for all the gametes responsible for generation V and thereby for all the dwarfs. This incriminates the pair 1-1 plus 1-2 as being responsible for gene transmis- sion through members of their two litters 11-1 to 7 and 11-8 to 16 although the path through 11-17 and 111-2 cannot be excluded. The male 1-2 has to be a heterozygous carrier due to the Occurrence of dwarfs A and B in the litter sired by 1-2 in connection with father-daughter mating. In contrast to 1-2 the female 1-1 was not a likely carrier of the gene because she gave birth to 16 phenotypically normal offspring sired by 1-2. In generations 11,111, and IV are indicated nine descendants of 1-2 which must be regarded as heteroiygous carriers.

In a previous publication the recessive gene for pituitary dwarfism in German Shepherd dogs was designated by the small case letter d and its normal

allelic counterpart was designated by D (ANDRESEN and WILLEBERC 1976). Although genetic homology of the dwarfism in German Shepherd dogs and

Table 1. Test of simple, autosomal recessive inherit- ance of pituitary dwarfism in Carelian Bear-Dogs

Sibship' Normal' Affected

Obs. Exp. Obs. Exp.

A, B 4 4.175 2 1.825 C 5 4.175 I 1.825 D. E 7 6.567 2 2.433 H, 1 7 6.567 2 2.433

Total 23 21.484 7 8.516

Chi-square test: ~ ' ,~ ,=0 .36 ,0 .50< P<0.70

' Designation of sibship refers to the respective dwarf(s). ' The proband litters and four additional individuals in generation V (cf. Fig. I ) were omitted from statistical treatment.

234 BRIEF REPORTS Hereditas 84 (1976)

Fig. 2. Two Carelian Bear-Dog dwarfs, approximately 1; and 1 year of age, and a phenotypically normal adult dog ot'the same breed. The dwarf's were the two full-sib probands designated by F and G in Fig. I . (P . Thomassen. photo)

Carelian Bear-Dogs has not been demonstrated by relevant test-matings the same gene symbols may be used because genetic homology is plausible. This is due to the observation that crossing with German Shepherd dogs was clearly manifested among Care- lian Bear-Dogs at dog-shows in the Carelian area of Finland in 1943 and 1944 (INGBERG 1960). As the gene for dwarfism in German Shepherd dogs has been traced to about 1940 it is justified to assume that copies of the same gene are present in the two breeds.

. 4 ~ k n o ~ i ~ l e r / ~ ~ e n / u . ~ Our thanks are due to Dr. Klaus Fame Madsen for calling our attention to the probands. The owners of affected dogs and Danish Kennel Club kindly provided information about the pedigree.

Departments of Animal Genetics and Forensic and State Veterinary Medicine, Royal Veterinary and Agricultural University, Copenhagen, Denmark

Literature cited

ANDRESEN. E. 1974. The effect of ascertainment by truncate selection on segregation ratios. ~ I World Congr. Genetics Applied to Livestock Production, Vol. I I I . Madrid. p. 111-114

ANDRESEN, E. and WILLEBERC. P. 1976. Pituitary dwarfism in German Shepherd dogs: Additional evidence of simple, autosomal recessive inheritance. - Nord. Vererinaermed. 28: 481-486

ANDRESEN. E.. WILLEBERC. P. and RASMUSSEN. P. G . 1974. Pituitary dwarfism in German Shepherd dogs: Genetic investigations. - Nord. Vererinaermed. 26: 692-701

INCBERC. K. E. 1960. Lidt om den Karelske Bjernehund. - Hunden (Medlemsbl. Dansk Kennel Klub) 70: 95-98

WILLEBERG. P.. KASTRUP, K. W. and ANDRESEN. E. 1975. Pituitary dwarfism in German Shepherd dogs: Studies on somatomedin activity. -- Nord. Veterinaermed. 27: 448-454

Erik Andresen Department of Animal Genetics Royal Veterinary and Agricultural University Bulowsvej 13 DK-1870 Copenhagen V. Denmark