Following previous formulations of a model of qualitative analysis of twin population data independent of zygosity, a new Bayesian approach has been developed. The present model can be applied to any qualitative genetic trait in twin population data, provided no specific source of variation be introduced by the twin condition, and allows not only estimation of the frequencies of mono- and dizygosity as well as the gene frequencies, but also verification of the trait's mode of inheritance.

The biometrical genetical method of analysis of continuously varying human traits is described and shown to unify a number of common approaches to the analysis of twin data. The method, which is based on the analysis of variance, goes beyond alternative approaches by providing tests of basic assumptions and by investigating the possibility of assortative mating and dominant gene action.

Twins form an indispensable group for the application of the biometrical genetical method but the value of including other groups, often more easily collected, is demonstrated.

The techniques are illustrated through the reanalysis of data on the behavioural measures, neuroticism and intelligence quotient (I.Q.). For both measures fundamental assumptions are met. The results suggest the absence of dominant gene action for neuroticism, indicating an evolutionary history of stabilising selection, and directional dominance for high I.Q., indicating an evolutionary history of strong directional selection. Both these findings seem reasonable in view of psychological knowledge concerning the two measures.

In the beginning the dogma was that sex determination in man followed the Drosophila pattern in which XO is male, XXY female, and the Y chromosome has no direct influence on the determination of sex. On the grounds of specific anomalies with which they presented, females with Turner Syndrome were sex chromatin tested and found to be chromatin negative [1]. This result, confirmed in 1956 by the male frequency of red-green colour blindness in these subjects which indicated that they carried only one X chromosome in spite of their female phenotype, suggested that therefore they might be XO, and, so, hinted that sex determination in man might not follow the then accepted pattern [2]. In 1959 chromosome studies confirmed that XOs were female [3] and showed that subjects with the symmetrical XXY sex-chromosome anomaly were with Klinefelter syndrome [4]. In the same year, by showing that XOs were females also in mice [5] it became accepted that the Y chromosome was the determiner of the formation of the testis in the mammalian embryo, and so was the key element in primary sexual differentation. It would seem appropriate to call this formal model of chromosomal sex determination the Malandrium pattern [6].

In 1966 Jacobs and Ross [7], from work on males with Y chromosome deletions narrowed down the testis determining function of the Y chromosome to its short arm. Then, in 1975, Wachtel and collaborators [8] were the first to formulate a hypothesis on the sex determining gene, or, more precisely on the nature of its product. They suggested that this developmental role might be played by the H-Y antigen, a weak histocompatibility antigen which had been known to be involved in the rejection of male skin grafted onto otherwise histocompatible female mice. The idea had run into technical difficulties and a major problem was related to the significance that should be attached to the results of two different ways for demonstrating the antigen, namely the cell-mediated cytotoxicity test or the serological test. Efforts were made to keep the H-Y hypothesis alive, largely because there was a certain elegance about it [9, 10]. However eventually XX male mice, lacking H-Y by either test, spelt the end of the candidature of H-Y as the testis determining mechanism [11, 12].

The lecithin/sphingomyelin ratio showed no difference between the two amniotic sacs in 24 multiple pregnancies examined before the onset of labor. Once labor started, however, the L/S ratio was higher in the first sac compared to the second in the six pregnancies where labor had commenced and was somewhat advanced at the time of amniocentesis. Dual-sac amniocentesis is essential during labor when assessment of pulmonary maturity is required, whereas single-sac sampling is adequate before the start of labor.

A method for the estimation of genetic correlations based upon analysis of genetic marker phenotypes is presented. At a given marker locus, the probability of observing a pair of individuals with a specific combination of phenotypes can be expressed as a function of the gene frequencies at that locus and the genetic correlation (R) between that pair. The likelihood of obtaining a sample of n such pairs with their phenotypes at m marker loci can be expressed as a product of nm such functions. From the likelihood function, maximum likelihood estimates of R can be obtained, and hypotheses about R may be tested. A sample of Swedish twin families (61 dizygotic twin pairs, 268 husband-wife pairs, and 164 sib pairs) were analyzed by this method using information from 21 markers. It was found that for the twin pairs, R = 0.458, which was significantly different from the R calculated for sib pairs (R = 0.5 58) but not significantly different from the expected 0.5. For the husband-wife pairs, it was found that R = 0.086, which did differ significantly from the expected value of 0, indicating the presence of nonrandom mating in this population.

Monthly chromosomal analyses have been carried out, from December 1971 to November 1972, on 4 male subjects aged 22 to 32. Over a total of 4 710 mitoses examined, the rate of aberrant cells (including gaps) was of 9.1% and there was no difference among individual yearly mean values. The average mitotic index, evaluated on 48 cultures, was of approximately 55‰. Significant differences (P < 0.025) have been found among individual yearly mean values (40-69‰). No seasonal increase of aberrations has been found; however, 12 of the 16 tetraploid cells were found in the winter months. In all subjects, the mitotic index reached its maximum in April-June (P < 0.001). The mitotic index and the percentage of aberrant cells were not shown to be correlated.

The introduction of informatics in the study of hereditary diseases, i.e., the birth of informatic medical genetics, marks a turning point in the history of medicine.

The biological informatics is the product of molecular genetics on one hand, and cybernetics on the other. The former has brought the study of the hereditary phenomena to the level of nucleic acids; while the latter, originally devised to the service of automation, reflects a number of fundamental biological phenomena, also at the molecular level.

The informatics of hereditary diseases is referred to a damage of the operative units acting to secure the development and homeostasis of the organism. The mechanistic conception of the damage is complemented by the energetic and chronologic concept.

On such foundations a modern conception of the genetics of diabetes is thus formulated. The clinical inadequacy of the static genealogical model is stressed, and the introduction of a dynamic model is suggested, taking into account the gradual chronological extinction of the normoglycemic genotype.

Adenosine deaminase (ADA) isoenzymes in a Swedish population of 342 unrelated individuals have been determined according to the method of Spencer et al. (1968). The gene frequencies found were 0.9357 and 0.0643 for ADA 1 and ADA 2 respectively. These frequencies are in good accordance with previous investigations.

The concept and definition of constitutional pathology. Genetic erythropathies such as constitutional spherocytosis, leptocytosis, ovalocytosis and drepanocytosis and their relation to hemolytic clinical syndromes are discussed. Sickle cell trait, sickle cell anemia, and sickle cell disease have to be distinguished as clinical manifestations of drepanocytosis. They represent a special variety of a « status degenerativus » (Bauer). Four genetic types of human hemoglobin have so far been identified that differ from each other by their molecular architecture and chemical reactivity. Several constitutional abnormalities of erythropoiesis other than those just mentioned are discussed: a hereditary defect in hemoglobin synthesis; erythroid multinuclearity; acanthocytosis; Fanconi's syndrome of hypoplasia and abiotrophy of the bone marrow as another variety of a status degenerativus.

Among the 85,976 children born at the «Istituto Ospitaliero Provinciale per la Maternità di Milano» from January 1st 1942 through December 31st 1962, 1185 newborn infants have

been observed with one or more congenital malformations, i. e. with a frequency of 13,8°/°°. Distribution of this material in a first period of six years and in three subsequent quinquennia, and comparison of the frequencies of the subjects with malformations observed in the various periods allow us to draw the following conclusions:

1) in the period 1942-1962, especially in the latest years, the total frequency of congenital malformations has not exhibited significant variations;

2) the frequency of harelip and/or cleft-palate, omphalocele, hypospadia, polydactily, hypodactily and syndactily appears rather uniform. The same applies, as a whole, to CNS malformations, though a certain heterogeneity has been found in the frequencies of rachischisis observed in the various periods;

3 ) as for mongoloid, dysmyelitic and club-foot subjects a significant heterogeneity of the frequencies observed in the various quinquennia has been demonstrated.

The cytotoxic effects of hydroxyurea and of related hydroxamic acid derivatives in vivo are briefly described. They occur selectively in tissues with high rates of cell renewal and they are of brief duration. Tissue concentration of hydroxyurea diminish rapidly as the result of renal excretion and metabolism; there is a close temporal relation between the physiological disposition of the agents and the cytotoxic changes. Hydroxyurea induces an immediate inhibition of DNA synthesis in proliferating tisdsues such as thymus, small intestine, and regenerating liver. Autoradiographic studies of mouse duodenum using tritiated thymidine have shown that the lethal susceptibility to hydroxyurea is restricted to cells in the S-phase of the mitotic cycles. Cells in G1, G2, and M are not damaged by the agent.

Levels of immunoglobulins IgG, IgA, IgM and IgE were determined in 8 MZ and 14 DZ twin pairs at the ages of 6-11 years, 12-17 years and 15-20 years. Intrapair similarity in immunoglobulin levels was found to be higher in the MZ than in the DZ twins, especially in the case of immunoglobulins IgA and IgM.

When calculating the chance of monozygosis from the results of a blood group study in a twin-family, it is desirable to use the complete information that is presented by these results and not only part of it.

A calculation-method in which the complete genetic-information is used is presented.

The use of the formulas is demonstrated by calculating the probability of monozygosis in two examples.

The material covers 332 twin pregnancies (including 5 of triplets) of which 208 (62.7%) were premature deliveries and 124 (37.3%) deliveries at term.

Of the twin pregnancies included in the group examined 15.7% developed complications (gestosis and eclampsia, kidney and heart diseases, anemia, hydramnios). Spontaneous deliveries were 66.7%, operative deliveries 33.3%. A high mortality of the second twin (13.1%) is noticeable and it increases to 21.4% when operative procedures are applied to the first twin.

A total of 400 DZ and 76 MZ twin pairs were studied for: maternal age, in which no significant differences were found; birth order, which was significantly higher in DZ twins; weight at birth; frequency of ABO blood-group phenotypes, where no significant differences were found; and, lastly, frequency of twinning in relatives, where, there was significantly higher occurrence, namely in siblings of probands.

Weights of developing incisors in 10 pairs of twin fetuses have previously been related to ages in order to compare dental growth status (Stack, 1963). Ages (T0) at which weights (W) of mineralised portions of teeth of the temporary dentition become significant have been computed (Stack, 1968), using a Fortran program giving maximum likelihood estimates of the required parameters, based on the statistical model of Angleton and Pettus (1966).

Availability of the additional parameter T0 allows a reexamination of the previous data, now fortified by observations on incisors from five further pairs of twin fetuses. Estimates of ages were made from the relationship (T—T0) = k·W½, where values for upper and lower central incisors were 2.0 and 2.8 for k, 19.5 and 18.5 for T0, respectively. Less reliable estimates were obtained from the lateral incisors. These values were computed from observations on 40 dentitions from normal singleton fetuses. Ages were also estimated from tabulated body weights (Documenta Geigy).

The AA. state that favism as a disease but is not inherited the underlying biochemical rer cells defectis. The defect is present in 12,1% of the sardinian population (immigrated in Genova) and is absent in subjects of ligurian extraction. A remarkable number of sensitive subjects have no clinical disturbances at all. The inheritance is of dominant mendelian type. In the females there is a low gene penetrance and expressivity. Even if apparenty normal to the biochemical tests they frequently transmit the defect to the sons.

The possibility of a sex-linked hereditary transmission is taken into consideration.

The Authors have studied the blood iron level in 94 twins (23 MZ and 24 DZ pairs) aged from 6 to 14 years.

Through the determination of the blood iron level a mean value of 45,59 mgs per 100 cc. of blood has been established. This value corresponds to that of single-born children of the same age; thus, the anemia ferri priva observed by Woodruff in twins during the first year of age may not apply to ensuing ages.

The comparison of the blood iron level at the ages taken into consideration has shown a slights progressive lowering of the blood iron, which the Authors consider physiological. The comparison of the blood iron level between MZ and DZ twin-pairs has not revealed a significantly different behavior. The twin test appears thus to demonstrate that the blood iron level is not genotypically determined, but is environment-conditioned, generally through thermic and gaseous exchanges between the organism and the environment in which it lives.

The behavior of 120 full term and 160 preterm newborn twins was assessed in several key areas: Irritability, soothability, reactivity, reinforcement value, and activity level. Infants were assessed during various situations so that aggregate, or summary, scores representing each behavioral area could be obtained. Evaluations were made during a feeding period, an active sleep period, an awake alert period during which orienting and interactional behaviors were observed, a quiet period during which reactivity to stress was observed, and any fussy periods during which irritability and soothability were assessed. Significant within-twin-pair concordance of behavior was obtained for each of the areas of behavior, suggesting the influence of constitutional variables on neonatal behavior. Analysis of these data by sex resulted in significant within-pair concordance of behavior for same-sex but not for opposite-sex twins. The actual ratings on these behaviors differentiated between full term and preterm infants. Increased behavioral deviance was observed with increasing prematurity in the areas of soothability and activity level. The results are discussed in terms of increased risk factors for preterm twins.