The switching of genes from the silent to the operating condition following a rigorous temporal sequence may be called “chronology of the gene”. The succession of times and its biocybernetic mechanism are peculiar to each species, but the duration of information exhibits wide intraspecific variations between populations, families, and individuals. The highly isochronic behavior of MZ twins is proof of the existence of an individual temporal constitution.

Our previous studies have proved that the duration of each information is a property of the corresponding genotype, depending on its potential time of activity (chronon), which depends in its turn on the same genotype's energy of stability (ergon).

In terms of molecular genetics, the stability against mutation of each gene, governing its Ergon/Chronon (E/G) system, is a function of three factors:

(1) Code degeneracy, i.e., the different stability of synonyms coding for the same information through different ratios of GC and AT bases, the former being the more stable.

A survey of chromosomal abnormalities has been carried out in Italy since 1966. Among the 1,551 subjects examined, the following abnormalities were found: 2 cases of C/C translocation, 1 of D/C, 5 of D/D, and 9 of D/G; 2 cases of Patau's syndrome with D trisomy; 4 cases of Edwards' syndrome; 176 cases of Down's syndrome, of which 163 with regular trisomy, 4 with mosaicism, 7 with D/G translocation, 1 with G/G translocation, and 1 with C/G translocation; 10 cases with 47,XXY complement; 1 case with 46,XY/47,XXY/48,XXXY mosaicism; 4 cases with 45,XO karyotype; 3 with 45,XO/46,XX, 1 with 45,XO/46,XY, 2 with 45,XO/46,XXr and 1 with 45,XO/46,XXi mosaicism; 2 cases with 47,XYY complement; 2 phenotypic females with 46, XY karyotype; and 5 leukaemic patients with Ph chromosome.

Furthermore, several kinds of normal variants were observed, such as no. 9 prominent secondary constriction, chromosome-D or -G enlarged short arm, 16-pair heteromorphism, Y-chromosome polymorphism, and satellited E chromosome.

The effect of Chlormadinone on the proliferation of Ehrlich ascites tumour was studied by employing the stathmokinetic method. In a high percentage of female mice carrying the tumour and treated by Chlormadinone an increase in tumour cell proliferation was observed, while in a few animals the proliferative activity was decreased.

No significant changes were observed in tumour cell proliferation in the male mice.

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.

The frequency of structural chromosomal aberrations has been examined in peripheral blood lymphocyte cultures from 18 normal individuals. A mean rate of aberrations was observed of 7.38%, and a mean breakage/metaphase index of 0.036. Individual values ranged, for the aberration index, from 4% to 15%; and, for the breakage/metaphase index, from 0.00 to 0.08. Only gaps and breakage were observed. The translocation cross and chromatid-ring observed derive from a series of experiments on homologous plasma cultures. As for the influence of different cultural environments, it has been observed that the rate of spontaneous aberrations behaved independently from the age of the blood sample, from the addition of penicillin in the culture, and from the concentration of phytohemoagglutinin. Using veal's fetal serum, the rate of aberrations failed to show any variation, even with a time of culture prolonged up to 96 hours; while, using homologous plasma, the time of culture having been prolonged, structural aberrations have shown a considerable increase. The study of the mitotic index in the different cultural conditions has indicated the possibility of favoring the growth of leucocyte cultures.

The following problems are briefly mentioned and discussed in this paper: (i) the role of genetics in public health, both in developed and in developing countries; (2) genetic aspects of the differential geographical distribution of diseases; (3) clinical and etiological aspects of malformation syndromes; (4) nosological complexity and phenotypic spectrum of these syndromes, with special reference to ectodermal dysplasias; (5) some problems of modern human communities.

A review of 62 cases of leukemia in twins reveals most cases occurred in MZ twins, although diagnosis of zygosity was at times admittedly questionable. Concordance was clearly highest in MZ twins of the perinatal-congenital period. This tendency was not maintained at later stages of life.

The older concept of a human placental barrier has been greatly modified. Tracer substances have demonstrated that leukemic cells pass the placental barrier. Materno-fetal transmission of leukemia is well known; all forms of murine leukemia can be transmitted similarly from generation to generation. Certain requisites effect the transmission of neoplastic-hematopoietic disease during pregnancy. Rare cases are reported of pregnant women with leukemia who bear children in whom clinical leukemia subsequently develops. The maternal diagnosis was made at the time of, or shortly after, delivery, suggesting an evolution of the maternal disease late in pregnancy.

That both partners of a pair of twins, either MZ or DZ, can become ill with leukemia within days or months of each other, appears more than coincidental. Chromosomal defects, common environmental factors, and conjoined intrauterine circulations may be important in the transmission of leukemia from one twin to another, a theory supported by the frequent concordance during the first year of life.

In the complex interactions of genetic and environmental factors, time represents a coordinate. Thus, it is only logical to consider biological phenomena and features in the three dimensions of space and in the dimension of time. Gedda and coworkers devoted much attention to the genetic aspects of various chronobiological events in man, and performed an extensive series of experiments to probe the many ramifications of gene-related timing phenomena.

Time factors in cytogenetics and neoplasia are discussed by considering chronobiological events as manifestations of interconnecting oscillatory phenomena in living systems. These phenomena, in turn, are regarded as the products of negative feedback control processes.

Subjects under discussion include satellite association, nondisjunction, C-mitotic duplication, endomitosis, endoreduplication, and delayed fertilization. The different theories of carcinogenesis are briefly reviewed and the time factor, as it applies to postulated mutational changes in neoplasia, is discussed.

An account is given of a family identified by a newborn malformed male. The chromosome anomalies described are interpreted as indicating that the father has a balanced translocation with a reciprocal exchange between no. 9 and no. 12. The supernumerary chromosome resembling a group F element, which is found in the propositus, is in fact one of the two rearranged chromosomes present in the father. The propositus therefore is trisomic for part of no. 9 and no. 12. His brother has a normal karyotype. Possible meiotic situations leading to the formation of the observed karyotypes are discussed.

The relationship between hypodontia and birth weight was investigated in 262 twins from the naval recruit population at Great Lakes. The overall frequency of hypodontia including third molars was 34.8%. Excluding third molars, hypodontia frequency was 11.6%. Anatomic distribution of congenitally missing teeth and frequency of third molar hypodontia were similar to other studies, but hypodontia of teeth other than third molars occurred two-three times as frequently in twins as in the general population.

The frequency of low birth weight (2500 g or less) in the twin sample was 47.7%. Hypodontia occurred more frequently in twins with low birth weight (42.6%) than in twins with birth weights over 2500 g (28.6%). Mean birth weight of twins with hypodontia was 2479 g, and without hypodontia, 2675 g. Twins with missing teeth other than third molars had a mean birth weight of 2357 g.

Mean birth weight was lower and hypodontia frequency was higher in MZ than in DZ twins. Discordances in anatomic location and number of missing teeth occurred in several MZ and DZ twin pairs. Discordances within MZ sets tended to be related to anatomic location rather than number of missing teeth. Six twin pairs (5 MZ and 1 DZ) out of 20 (13 MZ and 7 DZ) having one or more missing teeth had perfect concordance in both number and location of missing teeth. In 28 pairs neither member had hypodontia.

Mean intrapair variance in number of congenitally missing teeth was almost ten times greater in DZ than in MZ pairs, indicating the presence of a strong genetic component in connection with tooth number variability in twins.

Genetics deals with ordered and directed biological change in time; psychiatry with the development or the breakdown over the human life span of thought, feeling, and social adaptation. With the growing acknowl-edgement of the contribution of the genotype to mental and emotional uniqueness, it is appropriate to con-sider chronological parameters of mental disease in a genetic framework. These parameters include age of onset of illness (in turn affecting clinical characteristics), sequence of morbid signs and symptoms, length of illness, periodicity of illness, and temporal relation of clinical episodes to other biological events. Data are reviewed from twin and family studies, retrospective and ongoing, that relate such time phenomena to genetic factors in psychiatric disorder. Among the conditions to be considered are schizophrenia, manic-depressive psychosis, Huntington's chorea, karyotype abnormalities, presenile and senile disease, and the psychobiological ageing process itself.

The first-degree relations of 433 rheumatic propositi were examined for evidence of rheumatic fever (RF) or rheumatic heart disease (RHD). The families of 470 control propositi were examined in identical fashion. Of the total propositi, 378 propositi were matched with 378 control propositi for sex, age group, and ethnic community (European or Afro-Asian origin). Of 738 sibs of rheumatic propositi, 19.6% had RF or RHD and of 586 sibs of controls, 3.1% had RF or RHD (P<0.001).

In the matched families 2,985 first-degree relations of the propositi were examined: 142 had RF and 141 had RHD, a total of 9.5%. In the members of the families of the rheumatic propositi 232 rheumatics were found in 1,486 first-degree relations (15.6%), while in the control families 51 rheumatics were found among 1,499 (3.4%).

Comparisons and analyses were made of expected and observed numbers according to sibship size using the method of truncated analyses (Lenz-Hogben method). This analysis supported the hypothesis of a simple mendelian recessive inheritance. Unbiased estimates of P, the population frequency of affected individuals, were consistent with the value P = 0.25, expected for a mendelian recessive character. The rheumatic fever clustering in families in this study was compatible with a simple recessive mendelian inheritance.

Ten (eight MM and two FF) MZ twin pairs, with one or both schizophrenic members, have been examined. The disease was concordant in four pairs, discordant in one pair, and partly concordant in five pairs.

The time of onset was simultaneous in five pairs, but showed differences of three years in two pairs, and of one-two years in two more pairs. Concordance in the time of onset was not related to severity of the disease.

Two members of an Italian family are affected with progressive spinal muscular atrophy. One, a male, has had the disease since his early infancy and, though severely disabled, is still living at the age of 13. In his sister, the first symptoms appeared at the age of 15, and the disease seems to be rapidly advancing. Their parents were consanguineous. Their mother, however, married twice, her second marriage being nonconsan-guineous and producing no affected children.

The study of this family and an analysis of the literature led to the following conclusions: (a) early onset of the disease does not necessarily mean that the course will be malignant; (b) the disease usually has a similar onset and course in subjects belonging to the same family.

In many families, however (and these have been examined in the present paper) malignant Werdnig-Hoffmann disease is found to coexist with the Werdnig-Hoffmann disease with a prolonged course, the Wohlfart-Kugelberg-Welander disease with infantile onset, and the Wohlfart-Kugelberg-Welander disease with juvenile onset. We feel, therefore, that from a genetic point of view all these forms should be included into one and the same group.

A fluorescence staining method of the male chromatin body in human interphase nuclei is described.

Respiratory distress syndrome occurred in 77 of 1,130 liveborn twins (1: 15) and appears to be more frequent than in singletons. This increase cannot be entirely accounted for by the higher prematurity rate of twins over singletons. In 46 twin pairs with at least one affected, there was a significantly higher concordance rate among MZ than DZ pairs, suggesting that genetic factors are of some etiologic importance in this disease.

A total of 1, 041 syphilis patients of both sexes and different ethnic origin (Chinese, Malay, and Indian) were investigated for the distribution of ABO blood groups and haemoglobin genotypes. There was no significant difference in the incidence of ABO blood groups and abnormal haemoglobins between disease and control series in any of the racial groups.

From the above series, 819 male patients were investigated for the incidence of G6PD deficiency. There was no significant difference in the incidence of this genetic marker in disease and normal series.

A total of 45 twin pairs (19 MZ and 26 DZ), with one or both members affected by essential Generalized Epileptic Attacks, have been drawn out of the Mendel Institute's twin file. Concordance was observed in 18: 19 MZ, but only in 3: 26 DZ twin pairs.

Analysis of the 18 MZ concordant twin pairs has shown (1) concordance of clinical form in 17 pairs, (2) concordance in the age of onset in 15 pairs, and (3) concordance of expression (frequency of generalized attacks) in 13 pairs.

For a diallelic autosomal character, the correlation between parental total score and offspring total score (known as the parent-offspring correlation) given by + √{s(1 + 3F)/[(s + 1) + F(3s − 1)]}, is used here to estimate F, the constant which is commonly interpreted as coefficient of inbreeding. When the family records include varying number of children, a reasonably good estimate of F is exhibited which agrees fairly with other available estimates.

A reanalysis is made of the data obtained in two surveys in Brazil, regarding the inbreeding load of Whites and Negroes. It is shown that the differences detected are probably spurious, and mainly due to environmental factors. The “total” inbreeding load estimated for the pooled sample showed nonsignificant difference between Whites and Nonwhites.