Abstract: Examination of the properties of ColE1 derivatives containing either deletions or insertions of transposable genetic elements, has enabled a functional map of plasmid ColE1 to be constructed.

Abstract: The patient described represents the first reported case of partial deletion 10q. The patient is compared to the partial trisomy 10q syndrome.

Abstract: CONTENTS

Abstract: Chromosome analysis of G-banded cells from nine individuals showed that 9qh+ chromosomes have an extra band in the h region in approx. 3 to 50% of the cells.

Abstract: The authors discuss the clinical and cytogenetic problems raised in two new cases of X-chromosome translocations.

Abstract: Properties of amylase of two strains homozygous for two different amylase variants of Drosophila rnelanogaster were determined. Amylase of larvae and adults of both strains showed a pH optimum around pit 7.0. The Amy I enz)alae showed a higher temperature stability. They differed in maximal activity (for Amy 1 Vma x = 26.2 mU/9, for Amy4, 6 Vma x = 128.9 mU/ 9) and Michaelis constants (for Amy 1 K m = 0.09% starch, for Amy a,6 K m = 0.25% starch). This means that the activity difference measured at saturating substrate concentrations will not vanish or will not be reversed at lower substrate concentrations. This supports the hypothesis that this difference in amylase activity will cause a selective advantage when the two strains compete for food and starch is a limiting factor.

Abstract: This beautifully produced pictorial atlas illustrates the cytogenetic and clinical features of the ever increasing number of new chromosomal syndromes. It is published at a time when geneticists and paediatricians are just beginning to associate the dysmorphic features seen in some mentally retarded infants and children with the more recently described specific chromosomal anomalies. Each chromosome is shown in both the unbanded and banded states and a map depicts what is known about gene loci assigned to that specific chromosome. It is, however, for the presentation of the anomalies that the clinician will want to acquire this atlas. The excellent clinical photographs showing children and infants with partial and complete aneuploidies will save the clinician the trouble of searching through the half-dozen genetic journals to see whether his patient's features fit those of a partial trisomy 9 or a 22. The only disappointing feature is that pictures are not annotated with a clear indication as to what dysmorphic features are being shown. One hopes that the atlas will be updated regularly. An English edition is published by John Wiley and Sons, New York.

Abstract: At least three strong histocompatibility (H) loci--the H-2K, H-2D, and H-21 (for review see Klein 1975)--have been demonstrated within the H-2 complex of the mouse, and additional subregions have been defined within the 14-21 region (Shreffler and David 1975). The products of individual loci differ in their physicochemical properties (Hess 1976), immunogenicity (McKenzie and Snell 1973, McKenzie and Henning 1976), and ability to induce enhancing antibody formation (McKenzie and Snell 1973, Staines et al. 1974, Davies and Staines 1976, McKenzie and Henning 1977a, b). The ease with which transplantation tolerance can be induced is related to the genetic disparity between the donor-recipient strain combinations (for review see Silvers and Billingham 1969). Which of the H-2 products might be a major obstacle to overcoming the tissue incompatibility is still unexplained, however. Antigens which stimulate in mixed lymphocyte culture (MLC) have recently been thought to provide the major barrier to tolerance induction in H-2-incompatible combinations (Brent et aL 1976, Brooks 1976). We have tested neonatal tolerance induction in six combinations of H-2-congenic strains in such a way as to provide differences in the entire H-2 complex or in only a small proportion of it. The results presented here indicate that tolerance induction is much more difficult when donor and recipient differ at the K region than when they differ at the D and/or 1regions. All mice were from inbred strains maintained at the Institute of Molecular Genetics, Czechoslovak Academy of Sciences, Prague. The following inbred strains, congenic resistant partner strains, and F 1 hybrid mice were employed: B10.A, C57BL/10ScSn (hereinafter abbreviated B10), B10.D2, B10.AQR, B10.A(2R), B10.A(4R), A.TL, A.TH, (B10.A x B10)F~, (B10.A • B10.D2)F1, (B10.A • B10.AQR)F~, [B10.A x B10.A(2R)]F~, [BI0.A • B10.A(4R)]F1, and (A.TL • A.TH)F r The H-2 genotypes of these strains are listed in Table 1. Tolerance was induced in newborn mice (up to 20 hours of age) by the intravenous injection of 1215 • 10 6 living hybrid spleen cells. Cell suspensions were prepared in Hank's buffered solution from spleens of 2-3-month old donors and injected in a volume of 0.07-0.09 ml into the orbital branch of the anterior facial vein. At 8-9 weeks, the neonatally treated recipients were grafted with the respective allogeneic tail skin, according to standard procedure (Billingham et al. 1954). Grafts were inspected daily the first 4 weeks after transplantation and twice a week thereafter. The success of tolerance induction depended on H-2 antigenic difference between donor and recipient.

Abstract: Our field is in a rapid state of evolution. The broader concerns of human genetics not of immediate medical interest such as behavioral genetics are often investigated by persons not trained or identified as human geneticists. Both medical genetics and human genetics in general have prospered when various biologic techniques have been applied to genetic concepts. A search for novel biologic methods may provide new insights and may bridge the gulf between Mendelian and biometric approaches in studies of behavior and of common diseases. Medical geneticists need to broaden their fields of interest to encompass other fields than those of pediatric interest alone. We need to attract more basic scientists. Our field is evolving from a largely research oriented science to a service-oriented specialty. This logical development is a sign of increasing maturity and makes available to the public the results of our research. The resulting stresses and strains need careful watching to prevent their slowing the momentum of our science which can contribute continued insights into the many problems of behavior, health, and disease.

Abstract: The targets of allograft rejection have been shown to be under the control of multiple histocompatibility (H) genes. Using the murine model, scientists have attempted to estimate the number of genes by which various strain pairs differ. Early estimates based on the percentage of rejection of parental strain skin grafts by F 2 and/or backcross mice were in the range of 14 to 17 (Little and Tyzzer 1916, Barnes and Krohn 1957, Prehn and Main 1958). These techniques suffered from two shortcomings: (1) because of the large number of H genes by which the parental strains differed, very few grafts were accepted and the resultant error was great, and (2) the technique allowed only one opportunity for crossover; therefore, multiple closely linked H genes behaved as one gene and the estimates were small. Bailey and Mobraaten (1969) minimized these two shortcomings by basing their estimates on the survival of skin grafted between partially inbred mice and from multiply backcrossed mice to parental strain mice. In both cases the number of surviving skin grafts and the opportunities for crossovers were increased manyfold. Using these techniques Bailey and Mobraaten estimated that strains BALB/cBy and C57BL/6By differ by 28 or 29 H genes. Brambilla et al. (1970) used fewer reductional matings and a prolonged observation period to increase the sensitivity of their system. They estimate that strains C57BL/6 and DBA/2 differ by 36 H genes (28 based on rejection by male recipients, 44 based on rejection by female recipients). In this study we have estimated the H differences between strain combinations C57BL/6J and DBA/2J, C57BL/6J and C3H/HeJ, and B10.D2/n and DBA/2Grf using the techniques described by Bailey and Mobraaten (1969) and extending the interval of observation. In addition, we have increased the sensitivity of the system by preimmunizing male graft recipients in the B10.D2/n and DBA/2JGrf combination, resulting in an estimate of 88 H-gene differences.

Abstract: A patient with partial trisomy 22 (PT22) is presented. Inheritance is presumed to be due to secondary nondisjunction in her mother, who has a balanced translocation t(11;22)(q25;q13). The problem of the phenotypic heterogeneity observed with this chromosome change is discussed.

Abstract: A family is reported with a segregating t(5;10)(q15;q11) translocation resulting in a child carrying trisomy 10p The clinical findings of the patient are compared with trisomy 10p and the Cri-du-Chat syndrome

Abstract: Over three years ago, based on data gathered in our separate laboratories we jointly proposed a modification of a theory originally put forward by Wu and Kabat (1970) that more than one gene encoded a single antibody variable region (Capra and Kindt 1975). We suggested that genetic information encoding the hypervariable region sequences was inserted into framework gene structures and, moreover, that this gene interaction is the primary mechanism by which antibody diversity is generated. More than ever, we believe that neither germ line nor somatic mutation theories adequately explain V-region diversity. Historically, as amino acid sequence data accumulated, somatic mutational theories became burdened by increasing numbers of subgroups; they now have the additional difficulty of dealing with idiotypic inheritance (Kuettner et al. 1972, Capra and Kehoe 1975, Eichmann 1975, Fathman et al. 1977). Multigene theories, which became less attractive with the discovery of V-region allotypes and phylogenetically associated residues, have recently become almost untenable, as evidence from DNA-RNA hybridization studies indicates that very few copies of variable-region genes exist in the germ line (Rabbitts and Milstein 1975, Farace et al. 1976, Leder et al. 1976, Tonegawa et al. 1976). We believe these seemingly paradoxical data can be reconciled more satisfactorily by postulating that a few genes encode framework sequences, and into these is inserted information encoding the hypervariable regions generating complete V-regions. Wu and Kabat (1970) originally proposed such a theory upon observing that hypervariable regions were interspersed amid areas of relative constancy in the variable regions of antibody light chains. We restated the concept of hypervariable insertion in light of our independent observations, which suggested that the framework and hypervariable regions were under separate genetic control (Kindt et al. 1973a, Capra and Kehoe 1974a). In our previous discussion of this subject, we enumerated data that supported gene interaction and suggested certain experiments to test this theory. It was pointed out that a precedent for gene interaction already existed in immunology since separate genes were thought to encode the variable and constant regions of immunoglobulin polypeptide chains. Since that time, Hozumi and Tonegawa (1976) have presented evidence that immunoglobulin V and C genes are physically separate in embryonic DNA but have undergone rearrangement in differentiated cells.

Abstract: Hypophosphatasia is an inherited metabolic disorder of bone, in which the underlying detect is a deficiency of bone alkaline phosphatase (Rathbun, 1948). Although Nadler (1968) showed that cultured human fetal cells express alkaline phosphatase activity, this has not been applied to the prenatal diagnosis of hypophosphatasia. We have recently been able to detect two cases of the congenital lethal form of hypophosphatasia prenatally in unrelated families. Amniotic fluid was obtained by transabdominal amniocentesis at about 16 weeks of gestation from patients, both of whom had had previous children who had succumbed to hypophosphotasia in the neonatal period. Cells were collected and cultured for three weeks, in parallel with cells ti'om controls wl-/o had amniocentesis performed for other clinical indications at about the same stage of gestation. The cells were harvested and washed twice with saline, and then homogenized by ultrasonic disruption. Alkaline phosphatase activity was measured with 4-methylumbelliferyl phosphate as substrate, the increase in fluorescence being determined with a recording fluorimeter. Compared with controls, alkaline phosphatase activity was low in cells from both patients at risk (Rattenbury et al. (1975) (Figure 1~. 6 0 0

Abstract: A synthesis of data in favour of a model of the superstructure of eukaryotic chromosomes is presented. The basic, independent features of the model are (1) the genetic material consists of one continuous DNA molecule which is coated with protein to form the chromosome; (2) various degrees of folding of the nucleoprotein fibre result in the different appearance of chromatin as euchromatin, heterochromatin, and entire chromosomes; (3) the haploid DNA is organized in a ring comprising all the chromosomes, which are connected by interchromosomal fibres; (4) specific segments of the basic chromosome fibre are organizer regions for attachment to the inner surface of the nuclear envelope. Data from electron microscopy, chromosome replication, partial chromosome pulverization, and the non-random distribution of chromosomes, induced claromosome damage and sister chromatid exchanges may be interpreted as evidence of chromatin/nuclear membrane organelles. It is suggested that the segregation of chromosomes in somatic cell hybrids may result from the lack of integration of the two different chromosomal superstructures, and that the breakdown of the superstructure may be the basis for the chromosome instability in tumor cells and other transformed cells. Clastogens may affect chromatin fibres particularly at their attachment to the nuclear membrane and induce a submicroscopic lesion in adjacent chromatids which may lead to exchange initiation. The deletion of part of a chromosome or the loss of one or more chromosomes may result from the formation of a smaller ring, which is left out of the superstructure. A change of the character of a nuclear membrane attachment site will lead to a change in chromosome morphology.

Abstract: Two polymeric genes of the Pisum genome, bif-1 and bif-2, alter the monopodial shoot structure of the pea plant into dichotomy. They show an unstable penetrance being influenced by environmental factors as well as by specific genes of the genome. Under moderate climatic conditions, the penctrance ranges between 40 and 80% while it goes down to 0% under hot and dry conditions. A high pcnetrance results in a seed production superior to that of the initial line while low penetrance influences the seed production negatively. The gene efr for early flowering and ripening reduces the penetrance of bifl. A further reduction occurs by incorporating gent ion for an increased number of ovules per carpel into the genome. Gene ion, however, influences the penetrance of bif-1 only in the presence of efr. Gene sg-I responsible for the reduction of the grain size stabilizes the penetrancc of bif-2. This stabilizing effect is also maintained under those environmental conditions which reduce the penetrance of bif-I down to 0%. The stabilization leads to an increase of the seed production per plant.

Abstract: The evolutionary relationships between 4 species of the nasuta complex D. sulfurigaster albostrigata, D. kepulauana, D. kohkoa and D. albomicans were studied by means of the examination and interpretation of hybrid salivary chromosomes. Eighteen paracentric inversions were shown to have been involved in the evolutionary divergence of these species. The gene sequence phylogenies for chromosomes I, IIL, IIR and III of this complex are presented together with photographs of the chromosomes of hybrid larvae.

Abstract: Streilein and Wiesner (1977) have recently reported that skin grafted onto previously splenectomized mice shows a shortened survival time. Specifically, these authors have found that removing the spleen from C57BL/6 female mice seven days prior to grafting them with syngeneic male skin results in graft median survival times diminished from 16.5 days for controls to nine days for a splenectomized group. Another study seems to conflict with this finding, however. Nemec and coworkers (1974) observed no significant differences in the time of onset, the duration, or the end of the rejection process between controls and mice splenectomized 14 days prior to skin grafting. These authors found, in addition, that hosts splenectomized only two days prior to grafting supported viable grafts significantly longer than did their controls. These two studies differ, however, in at least three important experimental aspects: the histocompatibility loci defining the antigenic stimuli (H-Y versus H-I), the site of graft placement on the host (body versus tail), and the time interval between splenectomy and grafting (seven days versus 14 or two days). We have conducted a set of grafting experiments which bears on the effects caused by the first two of these differences. Female C57BL/6By mice were either splenectomized or sham operated under sodium pentobarbital anesthesia. Seven days after surgery these mice received two orthotopic tailskin grafts (Bailey and Usama 1960). The donors of both of the grafts were either C57BL/6By males or B 6 . C H 1 b females (synonym HW80). Thus, the grafting scheme in this case can be represented as H 1 b ~ H 1 c, whereas the Nemec group (1974) used H U ~ 1-1-1 a. All hosts also received a single isograft. Starting one week after grafting, observations were made on alternate days for at least 40 days and twice weekly thereafter. Scoring was based on visual examination of the graft for its epithelial scale pattern, pigmentation, and hair. In the case of the more vigorously rejected male skin grafts, the survival endpoint chosen was the first day of a detectable difference between the condition of the test graft and an isograft, or for brevity, FSR (first sign of rejection). Typically, a brown discoloration accompanied by dermal disintegration was seen. A much weaker rejection of the HW80 grafts occurred. In most cases, one or more transient periods of epidermal flaking, mild discoloration, and hair loss was seen. Therefore, the parameters chosen to describe these grafts were both the first sign of difference between the appearance of the test grafts and the isograft and also

Abstract: The phenotype AK 3.3 in the isoenzyme system of human adenylate kinase has been found in two members of the Wayampi population of French Guiana.

Abstract: Data from several laboratories indicate that murine tumors of different etiology may express H-2-1ike determinants cross-reacting with those of normal allogeneic cells (reviewed by Parmiani et al. 1978a). In previous studies aimed at examining the relationship(s) between individual tumor-associated transplantation antigens (TATA) and alien histocompatibility-like antigens of methylcholanthrene (MCA)induced BALB/c fibrosarcomas, we noted that three of the studied tumors lost their immunogenicity in vivo in hybrids between either BALB/c and C57BL/6J (Invernizzi and Parmiani 1975) or BALB/c and C3Hf strains (Parmiani and Invernizzi 1975, Parmiani et al. 1978a). These results can be explained by either a sharing of antigenic determinants between TATA of the BALB/c sarcomas and normal antigens of the parental allogeneic strain of the hybrid (Invernizzi and Parmiani 1975, Oth et al. 1976, Martin et al. 1977), thus suggesting that TATA and alien histocompatibility antigens of the tumor are identical, or by a genetically based difference in immune response to TATA between BALB/c and certain of its hybrids. Here I present evidence for the latter hypothesis in relation to the in vivo immune responsiveness to the TATA of the BALB/c fibrosarcoma C-1. The C-1 fibrosarcoma was induced in a BALB/c/Dp female by subcutaneous (s.c.) application of MCA; the tumor had been carried in syngeneic mice for 20 passages when used in the present investigation. In addition to H-2 d antigens, the C-1 fibrosarcoma was found to express foreign H-2Kk-like specificities (Meschini et al. 1977, Meschini and Parmiani 1978, Carbone et al. 1978) and the individual, noncross-reacting TATA, whose antigenic entity was shown to be separated from the H2Kk-like antigens. In fact, transplantation immunity to C-1 could be regularly induced in (BALB/c • AKR)F 1 mice immunized with the tumor and genetically unable to recognize H-2K k antigens. The latter can elicit a humoral immunity in BALB/c mice (Meschini and Parmiani 1978), but were unable to generate effector lymphocytes. In addition, anti-H-2K k immunity could be prevented in BALB/c mice without affecting their capacity to reject, in a secondary immune response, a challenge by C-I tumor (Parmiani et al. 1978b). The in vivo antitumor immune response, therefore, only measures a cell-mediated immunity to the individual TATA of C-1. The mice used were bred in our animal colony, except for strains A.TL (TL) and A.AL (AL), which were kindly provided by Dr. Guido Forni (University of Turin); breeding pairs of BALB.B and BALB.K were obtained through the courtesy of Dr.

Abstract: The times of a high level of knowledge of the humanities and classical languages common to all physicians and scientists have long passed by, and so have the ages of linguistic discipline. To derma, the integumentum, is neuter in gender. The authors of the article in question have but perpetuated the mistake (s. Brocher et al., ref .)--which unfortunately appears as well in Leiber and Olbrich's \"The Clinical Syndromes,\" but this makes it in no way better. Gerodermia osteodysplastica would be correct, but otherwise Geroderma osteodysplasticum.

Abstract: Report on mosaicism of an additional deleted chromosome 8 in a 12-year-old girl. She exhibits several typical but minor features of the trisomy-8 syndrome. Her IQ is 77 (Hawik).

Abstract: On standard measures of IQ the average black usually scores approximately one standard deviation below the average white (e.g., Scarf et al., 1977). There is an ongoing controversy as to whether this is due primarily to environmental or genetic differences between the two populations I. Scarr et al. (1977) state that \" i f genetic, racial differences do contribute to average intellectual differences between blacks and whites, then those blacks with higher degrees of white ancestry should perform better on intellectual tasks than those with lesser degrees of admixture.\" They then design a study wherein the degree of white ancestry of black children, as determined by gene markers, is compared to their performance on intellectual tasks. Would finding a positive correlation lend convincing support to notions of white genetic superiority? No, for the study design of Scarr et al. rests upon a fundamental, untestable assumption. They assume that, in terms of intellectual function, those whites who contributed to black ancestry were a random sample of all whites. A genetic interpretation of a positive correlation assumes that miscegenous whites had genetic IQs superior to blacks because they were a representative sample of the general white populat ion--which, in turn, assumes that whites have superior genetic IQs. Thus, to conclude from a positive correlation that whites have superior genetic IQs, it is necessary to assume that whites have superior genetic IQs. Suppose miscegenous whites were not a random collection of whites. I f their IQs were similar to b lacks -and lower than other whites--there should be no genetic correlation between degree of white ancestry and intellectual skills. Therefore, any positive correlation would be ipso facto attributable to environmental forces. Would this necessarily mean that miscegenous whites had less genetic mental endowment than other whites? Of course not. Environmental theory assumes that group differences in IQ are due to environmental forces. Thus, if it assumed that blacks have lower apparent IQs due to environmental forces, it can