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Biomedical subjects

G Livshits

Publications and source records attributed to G Livshits.

84 records · Page 5Linked to original sources

Growth and development of bodyweight, height and head circumference during the first two years of life: quantitative genetic aspects.

Mother-offspring and sib-sib relationships enable estimation of the heritability coefficients (or more accurately, transmissibility coefficients) and the so-called 'genetic correlation' for stature (S), weight (W) and head circumference (HC) in Israeli infants from birth to about two years of age. Heritability coefficients for S and HC show a more or less defined trend towards increase during ontogenetic development. The family resemblance in weight remains relatively constant or independent of age. The genetic correlations between each pair of the characters studied were higher than the corresponding phenotypic ones and showed an obvious tendency to decrease with age. The environmental correlations (rE) between W and S and between W and HC increase significantly with age, while for S and HC they are independent of age.

Age Factors↗

Study of genetic variance in the fluctuating asymmetry of anthropometrical traits.

We have studied the fluctuating asymmetry (FA) of 8 bilateral morphometric traits in two-parent families, comprising 216 families with one newborn baby, and 60 families with two children (age range 5-18 years). Heritability was assessed by: (1) multiple regression analyses of the children's measurements on the mother's and father's measurements; (2) midparent-child regressions; and (3) sibling correlations. The extent of genetic determination of individual FA measurements was generally low, albeit statistically significant in some cases. However, even these correlations were inconsistent between samples and relatives. However, the mean FA values for all 8 studied traits showed positive and significant correlation between parents and children in two samples and in total. Additive genetic variance, calculated from multiple regression analyses and midparent-child correlations, was estimated to be between 0.25-0.30. Three multiple regressions (two for the separate group and one for the total sample) yielded a statistically significant value (between 0.21-0.33) also for the non-additive genetic component.

Adolescent↗

Relationship between physical traits and rate of some common illnesses in newborn infants.

The morbidity rates of newborn infants suffering from jaundice or urinary tract infections (UTI) as well as total morbidity were determined in morphologically different groups of 1088 newborn infants. On the basis of body weight, body length, head circumference and Quetelet's index; the surveyed neonates divided into a modal (MI = mean +/- 0.67 SD) and two extreme groups: small (SI less than MI) and large (LI greater than MI), for each variable. The results show that, in general, infants with high morbidity, including those suffering from jaundice and UTI, have lower values of all the mentioned morphological traits than do healthy infants. Discriminant analyses of sick and healthy infants (three pairs of comparisons) indicate that decreased weight at birth is typical for all studied categories of morbidity. An additional finding was that infants suffering from UTI or other types of morbidity (total morbidity) originate from small-sized families in which the parents are generally older and the mother tends to be short and overweight.

Anthropometry↗

Age-dependent changes in morphometric and biochemical traits.

This morphometric investigation was based on an anthropological cross-sectional study of five age groups in Israel: (1) newborn infants; (2) 7-year olds; (3) 18-29 years old; (4) 30-60 years old; and (5) 80 years and older. Fluctuating asymmetry (FA) of eight bilateral traits and coefficients of variation (CV) for 21 standard anthropometric traits were investigated in these groups. The results show that the values of FA and CV increase significantly among older people. The frequency of blood groups and enzymatic alleles (13 polymorphic systems), as well as heterozygosities (H), were estimated in two age groups: adults (33-45 yr) and old (80-85 yr) people. Gene frequency distributions conformed with the Hardy-Weinberg equilibrium and were similar in both these populations. Estimates of mean individual H were nonsignificantly lower in the old population.

Adolescent↗

Relationships between intrapopulational and interpopulational genetic diversity in man.

The bottleneck effect (or extended period of reduced population size) is known to increase genetic distance (D) substantially, and this can be a serious factor that disturbs the phylogenetic relationships of populations inferred from genetic distance estimates. The bottleneck effect is also known to be a factor that disturbs the hierarchial relationships of the fixation indices (FST) or the coefficients of gene differentiation (GST) in subdivided populations. To examine the extent of the bottleneck effect on D and GST in human populations, the D and GST values were computed for various groups of populations from around the world, and their relationships with within-population heterozygosities were examined by using gene frequency data for protein and immunological loci. The results obtained indicate that the D value between a pair of populations is negatively correlated with the average within-population heterozygosity. This suggests that genetic distance estimates for small populations are seriously affected by the bottleneck effect, and that phylogenetic trees should be studied by taking into account this factor. The bottleneck effect on GST was also revealed from examination of the total gene diversity HT and its components, interpopulational genetic variation (DST) and intrapopulational genetic variation (HS). That is, a large value of GST in small populations was sometimes associated with the decrease of HS rather than the increase of DST. Generally speaking, however, GST was larger when geographically distant populations were considered than when closely located populations were considered. When there is any trace of bottleneck effects, phylogenetic trees should be constructed by a method in which the rate of evoluationary change is allowed to vary from branch to branch.

Ethnicity↗

Genetics of human body size and shape: complex segregation analysis.

The genetic component in a mixed heritability model, including major gene, multifactorial and sibling environment transmissible components, was studied for some 20 anthropometric traits in two ethnically different samples. The first sample comprised 305 Mexican nuclear families, and the second comprised 83 Ashkenazi Jewish nuclear families living in Israel. All variables, after adjustment for age and sex, were subjected to principal-components analysis (PCA) in each sample separately. The mixed model of inheritance as implemented in the computer program POINTER was used in the present study. An attempt was made to evaluate genetic effects in the variation of the first principal components (PCs). PCA showed a clear separation of variables and was easily interpretable. The PC1 was a credibly general size factor. This factor alone accounted for about 30% of the total variance. Other components are rather shape factors for various combinations of traits. The testing of several genetic hypothesis showed the following: (1) For all factor scores the genetic component was high and statistically significant. (2) In a Mexican sample, for PC1 and PC2, both major gene and polygenes contributed significantly to the total variation of these variables; in the major locus the alleles were most probably codominant. (3) For all other PCs the major gene effect hypothesis was rejected, with more than 50% of the variation attributable to the polygenes contribution. (4) No evidence was found for sibling environmental resemblance in either sample.

Adolescent↗

Obesity and the risk of toxaemia of pregnancy.

The purpose of the present study was to examine the relationship between severe pre-eclampsia/eclampsia (toxaemia) and obesity. We collected sociodemographic, anthropometric, medical and pregnancy outcome data from the hospital records of 248 Israeli women diagnosed with either pregnancy-induced or chronic hypertension, and compared these data to a control group of 236 women. Univariate analysis showed that while there exists a statistically significant positive association between obesity and hypertension (both pregnancy-induced and chronic) obesity presents no added risk to the development of toxaemia. Furthermore, we found a significant decrease in the rate of obesity among primigravid versus multigravid mothers with toxaemia superimposed on pregnancy-induced hypertension. On the other hand, primigravid mothers with PIH were at an increased risk of developing toxaemia as compared to multigravid women. These results suggest that obesity is not a significant factor in the development of toxaemia.

Adult↗

Geographic variation in vascular mortality in Eurasia: spatial autocorrelation analysis of mortality variables and risk factors.

The geographic variation patterns of vascular mortality and their major risk factors from 68 samples in Eurasia are described in this work. The goodness-of-fit tests and analysis of variance indicate significant differences in incidence of mortality from the studied diseases, as well as in risk factors among the various geographic regions in four age groups. Correlation analysis points out the two general tendencies for the majority of studied traits: (a) significant positive association with latitude and (b) significant negative correlation with longitude. In turn, one-dimensional correlograms showed no specific geographic pattern at least up to 3000 km for all studied variables. However, at the large geographic scale a long-distance differentiation pattern was indicated for total serum cholesterol and body mass index; regional patches--for total death rate, mortality rate from cardiovascular and ischaemic heart diseases, systolic and diastolic blood pressure; and a local patches pattern was detected for mortality rate from stroke. Two-dimensional correlograms uncovered three distinct and significant patterns of variation: (a) a north-south trend for total mortality rate, for death rate from cardiovascular and ischaemic heart diseases, for diastolic and systolic blood pressure and for body mass index; (b) a northwest-southeast pattern for mortality rate from cerebrovascular disease; and (c) local patches for total serum cholesterol.

Adult↗

Genetics of human body size and shape: pleiotropic and independent genetic determinants of adiposity.

The present study utilized pedigree data from three ethnically different populations of Kirghizstan, Turkmenia and Chuvasha. Principal component analysis was performed on a matrix of genetic correlations between 22 measures of adiposity, including skinfolds, circumferences and indices. Findings are summarized as follows: (1) All three genetic matrices were not positive definite and the first four factors retained even after exclusion RG > or = 1.0, explained from 88% to 97% of the total additive genetic variation in the 22 trials studied. This clearly emphasizes the massive involvement of pleiotropic gene effects in the variability of adiposity traits. (2) Despite the quite natural differences in pairwise correlations between the adiposity traits in the three ethnically different samples under study, factor analysis revealed a common basic pattern of covariability for the adiposity traits. In each of the three samples, four genetic factors were retained, namely, the amount of subcutaneous fat, the total body obesity, the pattern of distribution of subcutaneous fat and the central adiposity distribution. (3) Genetic correlations between the retained four factors were virtually non-existent, suggesting that several independent genetic sources may be governing the variation of adiposity traits. (4) Variance decomposition analysis on the obtained genetic factors leaves no doubt regarding the substantial familial and (most probably genetic) effects on variation of each factor in each studied population. The similarity of results in the three different samples indicates that the findings may be deemed valid and reliable descriptions of the genetic variation and covariation pattern of adiposity traits in the human species.

Adipose Tissue↗

Segregation analysis of quantitative traits.

A review of advanced methods of segregation analysis of quantitative traits on human pedigree data is presented. Special attention was paid to formulation of genetic models tested in the analysis, to the possibility of statistical distinguishing between these models, to the power of the used transmission probability tests, and to the possibility of unambiguous interpretation of the analysis results.

Algorithms↗

Genetics of human body size and shape: evidence for an oligogenic control of adiposity.

In a previous study by the authors in each of the pedigree samples from Kirghizstan, Turkmenia and Chuvashia, four principal factors supposedly controlled by four non-overlapping gene subsets were found. About 90% of total variation of adiposity as assessed by 22 measurements of skinfolds, circumferences and indices were covered by these factors. This study provides results of segregation analysis of each of these four factors. By the usual transmission probability tests, major gene (MG) control was accepted in all 12 analyses--four traits in three populations. Some of the most parsimonious MG models included non-MG effects, such as correlation of residuals between spouses, between parent and offspring and between sibs. The Kirghizian samples showed a significant assortative mating effect as measured by the correlation between genotypic values at putative MG in spouses. The proportion of the trait variance attributable to the MG effect varied from 0.296 (factor F4 in the Chuvashia sample) to 0.596 (the same factor in the Kirghizian sample). It is assumed that four independent large-effect genes can be recognized in the genetic control of adiposity determining, respectively, individual predisposition to accumulate subcutaneous fat, its distribution between the body trunk and extremities, predisposition to accumulate inner fat and its distribution between the upper and lower body parts. In each population, unification of the four most parsimonious MG models forms oligogenic models explaining from 0.364 (Chuvashia) to 0.540 (Kirghizstan) of total adiposity.

Adipose Tissue↗

Quantitative genetics of circulating molecules associated with bone metabolism: a review.

This paper reviews recent advances in the studies of various biochemical factors (biomarkers) involved in bone metabolism and remodeling. The collected data in this area suggest the existence of complex and multilevel relationships between calciotropic hormones, various cytokines and growth factors. The paper summarizes the data on the magnitude of the familial and genetic effects on the interindividual variation in circulating levels of many of these biomarkers. The majority of the cited heritability estimates are well above 20%, reaching up to 80% for some cytokines (e.g., TNFalpha and VEGF). These estimates point to potential targets for the identification of novel quantitative trait loci involved in the control of the respective molecules variation. This information is of particular importance, because the available data on the association between specific genes/polymorphisms and the respective circulating molecules variation is still very limited. The paper also provides recent findings on the genetics of co-variation between the circulating levels of various biomarkers. It shows that only in a few instances, such as for example, between IGF-I and IGFBP-3, and IGFBP-1 and leptin, significant and substantial genetic (and environmental) correlations were found. It appears that despite the prominent strong genetic effects on variation of each of the numerous biomarkers, the pleiotropic effects are rather limited. We consider briefly some important new data obtained using the gene expression approach and microarray technique. The data, for instance, indicate that the genetic effects on bone metabolism appear to be an open system, which can be activated or modulated by external factors such as drugs, e.g., PTH. Extensive molecular genetic studies in this area are both timely and imperative to detect the specific genes affecting variation (and co-variation) of the circulating factors associated with bone metabolism.

Animals↗