A study on the inheritance of the transverse cephalic curvature index

The transverse cephalic curvature index defined by Dash Sharma (Proc. Indian Sci. Cong. 54:496, 1967) was studied in 38 families of both the Adivasi population of Orissa and the Andhras of Visakhapatnam (Andhra Pradesh). Correlation coefficients estimated for the different familial combinations gave a negative result, suggesting the non-hereditary nature of the index.     

Classification and inheritance study of transverse cephalic curvature index

In the present paper an arbitrary classification of the transverse cephalic curvature index has been proposed as low (up to 36.9), medium (37.0–39.9) and high (40.0 and upwards) on the basis of the study of 163 Punjabi families. The inheritance study of this index has been attempted by estimating the coefficient of correlation of the different familial combinations of 49 Punjabi families (all adults). The correlation coefficients observed for the different combinations suggest the hereditary nature of this index, but presently it could not be decided whether or not there exists any sex-influence or sex-limitation of the character, though population studies suggest significant sex difference.     

Family studies of IgA deficiency

Seventeen immunoglobulin A (IgA)-deficient subjects and other members from 13 families were examined at HLA-A, B and DR, C4A, C4B, and Bf loci. Of the 29 independent haplotypes in the IgA-deficient: subjects, 22 included deletions, duplications, or defects at the C4 or 21-hydroxylase loci. It is suggested that there may be a gene regulating serum IgA concentrations in this same region of chromosome 6. Three main supratypes explain most of the previously reported tHLA associations with IgA deficiency. These are A1, Cw7, B8, C4AQ0, C4B1, BfS, DR3, Bw65(14), C4A2, C4B1/2, BfS, and Bw57(17), C4A6, C4B1, BfS. All three are proposed to carry a gene for IgA deficiency, while other supratypes carrying the same B allele generally do not. Other supratypes possibly associated with IgA deficiency were also identified. A survey of about 150 individuals with at least 1 of the 3 main supratypes revealed only 2 IgA-deficient subjects, and these were among the 20 that had 2 of these supratypes. This suggests the possibility of a recessive mode of inheritance, with penetrance determined by another factor which is not major histocompatibility complex-linked. All the supratypes found in this group of IgA-deficient subjects would then carry the putative recessive allele for IgA deficiency.     

Family studies in common variable immunodeficiency

The occurrence of cancer, immunodeficiency, and diseases with possible autoimmune aetiology were studied in 355 blood relatives of 12 patients with common variable immunodeficiency (CVID). The family members were identified through the patients and interviewed after completing a questionnaire, their diseases were medically confirmed by local general practitioners. In two families consanguineous marriages were identified with the coefficients of inbreeding of 0.03125 and 0.01563, respectively: one patient, a dizygotic twin of an unaffected sister, was a granddaughter of first cousins, the second patient was the third daughter of second cousins. These cases of CVID strongly support the autosomal recessivity of the underlying genes. One male patient with CVID was shown to be related to a patient with X-linked hypogammaglobulinaemia, both sharing a common carrier. The different clinical courses of their diseases suggest two genetically determined immunodeficiencies and genetic heterogeneity. No family had an unusual clustering of cancer. The occurrence of tumours in the blood relatives of CVID patients was not significantly higher than in the relatives of spouse controls. Immunological examination of 30 first degree relatives of the CVID patients revealed three children (2 males and 1 female) with selective IgA deficiency, in one boy combined with elevated serum IgE level. Four relatives with rheumatoid heart disease, 12 cases of gastric or duodenal ulcer, and 14 relatives with thyroid disease represented the most often encountered diagnoses with a possible autoimmune component in their aetiology.     

Family studies of mephenytoin hydroxylation deficiency.

A genetic polymorphism characterized by deficient drug oxidation exists for the hydroxylation of mephenytoin. This deficiency was first recognized in a family study that suggested an autosomal recessive pattern of inheritance. To confirm the observation, we investigated 28 relatives of five poor metabolizers. Subjects ingested 50 mg of mephenytoin, and the 24-hr urine was analyzed for hydroxymephenytoin. The pedigree data shown here provide strong evidence that deficient mephenytoin hydroxylation is an autosomal recessive trait.     

Family and population studies on the human pepsinogen A multigene family

Summary Human pepsinogen A (PGA) displays highly polymorphic isozymogen patterns after polyacrylamide gel electrophoresis and activity staining. The patterns differ with respect to the presence and the relative intensity of the individual fractions. Family studies strongly suggest that these isozymogen patterns are encoded by allelic haplotypes, encompassing different numbers and types of PGA genes. In this paper, we confirm the essential features of this multigene model. We establish the relationship between the haplotypes and the corresponding isozymogen patterns by determination of the PGA polymorphism at both the DNA and the protein level in 117 Dutch individuals, 60 of whom were unrelated. The combination of HindIII and EcoRI restriction fragment length polymorphisms (RFLPs) has enabled us to define different haplotypes, which are shown to segregate within families. Most genes are characterized by their specific EcoRI fragments. The HindIII RFLP is in strong linkage disequilibrium with PGA genes showing strong expression of the relevant isozymogen. Although a general picture of the relationship between genotypes and phenotypes is emerging, there are exceptions, suggesting that rare haplotypes evolve by unique crossover events.     

Family studies of plasma dopamine-beta-hydroxylase thermal stability.

There are large individual variations in the thermal stability of human plasma dopamine-beta-hydroxylase (DBH). These variations are a characteristic of the DBH molecule itself. Individual subjects may be classified as those with thermolabile and those with thermostable plasma DBH. Of 362 randomly selected unrelated children, 8.01%, and of 238 randomly selected unrelated adult subjects, 5.46% had thermolabile plasma DBH. There was not a significant correlation of DBH thermolability with either sex or age on the basis of data from 230 adults and children in 53 randomly selected families. Subjects with thermolabile DBH had basal enzyme activity only about 55% of that in subjects with stable enzyme. There was not a direct relationship between DBH thermolability and the allele DBHL, the presence of which results in very low basal enzyme activity. There was a significant familial aggregation of the trait of DBH thermolability, but there was not a significant correlation of this trait among spouses. Although preliminary pedigree evaluation raised the possibility of monogenic inheritance of the trait of DBH thermolability by an autosomal recessive mechanism, three separate families in which both parents had thermolabile enzyme included offspring with thermostable DBH. All five of these offspring had very low basal plasma DBH and were presumed to be homozygous for the allele DBHL. These observations raised the possibility that the trait of plasma DBH thermolability may be inherited, and that there may be an interaction between the locus or loci responsible for thermal stability and the locus DBH.     

Observational learning of new movement sequences is reflected in fronto-parietal coherence

Mankind is unique in her ability for observational learning, i.e. the transmission of acquired knowledge and behavioral repertoire through observation of others' actions. In the present study we used electrophysiological measures to investigate brain mechanisms of observational learning. Analysis investigated the possible functional coupling between occipital (alpha) and motor (mu) rhythms operating in the 10 Hz frequency range for translating "seeing" into "doing". Subjects observed movement sequences consisting of six consecutive left or right hand button presses directed at one of two target-buttons for subsequent imitation. Each movement sequence was presented four times, intervened by short pause intervals for sequence rehearsal. During a control task subjects observed the same movement sequences without a requirement for subsequent reproduction. Although both alpha and mu rhythms desynchronized during the imitation task relative to the control task, modulations in alpha and mu power were found to be largely independent from each other over time, arguing against a functional coupling of alpha and mu generators during observational learning. This independence was furthermore reflected in the absence of coherence between occipital and motor electrodes overlaying alpha and mu generators. Instead, coherence analysis revealed a pair of symmetric fronto-parietal networks, one over the left and one over the right hemisphere, reflecting stronger coherence during observation of movements than during pauses. Individual differences in fronto-parietal coherence were furthermore found to predict imitation accuracy. The properties of these networks, i.e. their fronto-parietal distribution, their ipsilateral organization and their sensitivity to the observation of movements, match closely with the known properties of the mirror neuron system (MNS) as studied in the macaque brain. These results indicate a functional dissociation between higher order areas for observational learning (i.e. parts of the MNS as reflected in 10 Hz coherence measures) and peripheral structures (i.e. lateral occipital gyrus for alpha; central sulcus for mu) that provide low-level support for observation and motor imagery of action sequences.     

Peri-rolandic and fronto-parietal components of scalp-recorded giant SEPs in cortical myoclonus

Scalp topography of giant SEPs to median nerve stimulation was studied in 4 patients with cortical myoclonus of various etiology. The positive peak (P30) at the contralateral parietal area was simultaneously accompanied by a negative peak at the frontal area (N30), and at least one of these two peaks was enhanced in 2 patients. Another positive peak (P25) and a negative peak (N35) were also identified at the peri-rolandic area with different latency from P30 and N30, respectively, in all patients. N35 was enhanced in 3 patients, and P25 in 2 patients. It is concluded that, as seen in normal subjects, tangential (P30-N30) and radial (P25 and N35) components of SEPs are most likely distinguishable in giant SEPs, and that either one or both of those components is enhanced in different ways depending on the patients.