Population genetics study of differential fertility in humans (based on an example of habitual abortion). III. Distribution of individual heterozygosity and genotype combinations for 9 polymorphic loci

Distribution of individual heterozygosity (the number of heterozygous loci per individual), wife/husband genetical differences and frequencies of genotypes formed by paired combination of eight polymorphic loci were studied in a group of couples and single women with repeated spontaneous abortions, and in a group of couples with normal fertility. No statistically significant differences were found for the first two parameters. Marked increase of genetical variability was shown for the women with repeated spontaneous abortions, as consequence of elevation of frequency of rare genotypic paired combinations. Therefore, differential fertility, as a component of stabilizing selection, alters the distribution of complex genotypes in human populations.     

Population genetic study of differential human fertility (exemplified by habitual abortion). VI. Nonspecific risk factors for habitual abortion

The associations between variation of morphophysiological traits, biochemical and immunological loci and incidence of repeated spontaneous abortions were examined in Moscow population. Early age of menarche, great difference in wife/husband body length and the presence of rare genotypic paired combinations for 8 biochemical and 5 immunological loci have been shown to be the main nonspecific risk factors for this type of pathology. Direct estimations of relative risk are presented.     

Population genetic study of differential fertility in man (illustrated by habitual abortion). V. Distribution of individual heterozygosity and parameters of genotypic variability for a set of immunological genetic markers

Distribution of individual heterozygosity (the number of heterozygous loci per individual), frequencies of genotypes formed by paired combinations of 5 loci and values of linkage disequilibrium between 6 blood group loci were studied both in a group of couples and single women with recurrent abortions in anamnesis, and in a group of couples and single women with normal fertility. Statistically significant deficit of highly heterozygous individuals was found in the experimental group. Marked increase of genetical variability was shown for the women with repeated abortions, as a consequence of elevation of rare genotypic paired combination frequency. Therefore, differential fertility as a component of stabilizing selection alters the distribution of complex genotypes in human populations. Differences in values of linkage disequilibrium between women with repeated abortions and those of normal fertility were not found.     

Population-genetical study of differential fertility in humans (based on an example of habitual abortion). I. Approach to the problem and analysis of morpho-physiological and demographic traits

It was shown that women from the studied group of married couples, suffering from repeated spontaneous abortions (the main group), have earlier menarche and their husbands are taller, as compared with the control group of couples with normal reproductive performance. The degree of similarity between mates in age and stature appeared to be lower in the main group than in the control group. The variation of the characters under study is supposed to provide an auxiliary criterion in selecting couples at high risk of repeated spontaneous abortions.     

Population genetic study of differential fertility in man (illustrated by habitual abortion). IV. Distribution of blood groups and frequency of incompatible marriages

Hereditary variation of 5 immunological systems coded by 8 loci was compared in 148 couples and 100 women with repeated spontaneous abortions in anamnesis (experimental group) and 141 couples and 100 women with normal fertility (control group). Marked differences in distributions of genotypes and frequencies of 3 systems (MNSs, Rhesus, Duffy) and frequency of AB0-incompatible couples were found between control and experimental groups. An average value of observed heterozygosity in experimental group was lower, as compared to the expected value. Possible influence of immunological factors on recurrent fetal wastage is discussed.     

Peptidases II. Localization of dipeptidylpeptidase IV (DPP IV). Histochemical and biochemical study]

Fresh frozen, unfixed, chloroforme-acetone treated or freeze-dried cryostat sections or sections from aldehyde-fixed blocks of tissue were tried for the histochemical investigation of dipeptidylpeptidase IV (DPP IV) with L-glycyl-L-prolyl(gly-pro)-naphthylamides as substrates and stable or unstable diazonium salts for simultaneous coupling and various buffers, pH 5--7.5 in rats, mice, guinea-pigs, cats, rabbits, hamsters and human enterobiopsies. The best results are obtained with 1.7--3.4 mM gly-pro-4-methoxy-2-naphthylamide and 1 mg Fast Blue B/ml or (with some limitations) 0.025 ml hexazotized new fuchsine/ml in 0.1 M cacodylate or phosphate buffer, pH 7.5 and unfixed sections for the demonstration of the total activity of DPP IV and freeze-dried celloidin-mounted cryostat sections for the precise localization of the enzyme or the detection of lysosomes, Golgi apparatus and secretion granules sections from aldehyde fixed tissue blocks are only suitable to study the lysosomal hydrolysis of gly-pro-naphthylamides between pH 5 and 7 when hexazotized p-rosaniline or new fuchsine are employed. DPP IV is firmly bound to strutures and shows species- and organ-dependent differences. In general, the enzyme occurs in the capillary endothelium, sinusoidal cells, perineurium, epithelial cells of intercalated and striated ducts, microvillous zone of intestinal crypts and villi, uterus, Fallopian tubes, ductus epididymis and proximal renal tubules, hepatocyte and lymphocyte membrane, plasmalemma of pseudostratified and transient epithelia and in the capsules and interstitium of many organs. These sites of activity can be completely inhibited by diisopropyl fluorophosphate and partially by Pb2+; Mg2+, Mn2+, Co2+ EDTA are without any influence. Phenantrolin may activate DPP IV. The biochemical assay works with 10 mM gly-pro-2-naphthylamide in 0.1 M cacodylate buffer, pH 7; the enzyme activity is determined fluorometrically in guinea-pig and rat organs; the data confirm and enlarge the species- and organ-dependent differences revealed by histochemistry. Compared with other dipeptide as well as tripeptide and amino acid naphthylamides the results obtained for DPP IV suggest a peptidylpeptidase which seems to be involved in other metabolic processes beside the degradation of collagen.     

Natural variation in the Pto disease resistance gene within species of wild tomato (Lycopersicon). II. Population genetics of Pto

Disease resistance to the bacterial pathogen Pseudomonas syringae pv. tomato (Pst) in the host species Lycopersicon esculentum, the cultivated tomato, and the closely related L. pimpinellifolium is triggered by the physical interaction between the protein products of the host resistance (R) gene Pto and the pathogen avirulence genes AvrPto and AvrPtoB. Sequence variation at the Pto locus was surveyed in natural populations of seven species of Lycopersicon to test hypotheses of host-parasite coevolution and functional adaptation of the Pto gene. Pto shows significantly higher nonsynonymous polymorphism than 14 other non-R-gene loci in the same samples of Lycopersicon species, while showing no difference in synonymous polymorphism, suggesting that the maintenance of amino acid polymorphism at this locus is mediated by pathogen selection. Also, a larger proportion of ancestral variation is maintained at Pto as compared to these non-R-gene loci. The frequency spectrum of amino acid polymorphisms known to negatively affect Pto function is skewed toward low frequency compared to amino acid polymorphisms that do not affect function or silent polymorphisms. Therefore, the evolution of Pto appears to be influenced by a mixture of both purifying and balancing selection.     

An anthropobiological study in Basse Kotto (Central Africa). I. Erythrocyte and sero-genetic markers: an analysis of the genetic differentiation

Phenotype and allele frequencies for hemoglobin types (Hb beta), acid phosphatase (AcP), phosphoglucomutase (PGM1 and PGM2), esterase D (EsD), 6-phosphogluconate dehydrogenase (6-PGD), glyoxalase I (GLO), superoxide dismutase (SOD A), and adenylate kinase (AK) as well as for haptoglobins (Hp), group-specific component (Gc), transferrin (Tf), Gm, and Inv groups and albumin, are reported in the Mbugu, Sango, Yakpa, and Baya Mandja ethnic groups in the Basse Kotto district of the Central African Republic. The total sample size amounts to 133 males and 128 females aged from 16 to 60, unrelated and healthy. A new albumin variant (albumin Mbugu) is described and discussed. The average heterozygosity is high in each group because of a high degree of exogamy. the FST average standardized value among the four groups indicates that the genetic differentiation in Basse Kotto is at level of about 2%. This indicates that the four examined groups might be considered genetically homogeneous, in spite of their different ethnic origins. The genetic distances among the four groups show that only the Baya Mandja are less closely related to the other three groups because of their foreign origin.     

The Finland-United States investigation of non-insulin-dependent diabetes mellitus genetics (FUSION) study. II. An autosomal genome scan for diabetes-related quantitative-trait loci

Type 2 diabetes mellitus is a complex disorder encompassing multiple metabolic defects. We report results from an autosomal genome scan for type 2 diabetes-related quantitative traits in 580 Finnish families ascertained for an affected sibling pair and analyzed by the variance components-based quantitative-trait locus (QTL) linkage approach. We analyzed diabetic and nondiabetic subjects separately, because of the possible impact of disease on the traits of interest. In diabetic individuals, our strongest results were observed on chromosomes 3 (fasting C-peptide/glucose: maximum LOD score [MLS] = 3.13 at 53.0 cM) and 13 (body-mass index: MLS = 3.28 at 5.0 cM). In nondiabetic individuals, the strongest results were observed on chromosomes 10 (acute insulin response: MLS = 3.11 at 21.0 cM), 13 (2-h insulin: MLS = 2.86 at 65.5 cM), and 17 (fasting insulin/glucose ratio: MLS = 3.20 at 9.0 cM). In several cases, there was evidence for overlapping signals between diabetic and nondiabetic individuals; therefore we performed joint analyses. In these joint analyses, we observed strong signals for chromosomes 3 (body-mass index: MLS = 3.43 at 59.5 cM), 17 (empirical insulin-resistance index: MLS = 3.61 at 0.0 cM), and 19 (empirical insulin-resistance index: MLS = 2.80 at 74.5 cM). Integrating genome-scan results from the companion article by Ghosh et al., we identify several regions that may harbor susceptibility genes for type 2 diabetes in the Finnish population.     

Cytoarchitectonic study of the brain of a perciform species, the sea bass (Dicentrarchus labrax). II. The diencephalon

The cytoarchitecture of nuclei in the preoptic area, ventral thalamus, dorsal thalamus, epithalamus, hypothalamus, posterior tuberculum, synencephalon, and pretectum and the accessory optic nuclei was analyzed in a perciform teleost, the sea bass Dicentrarchus labrax, by using serial sections stained with cresyl-violet. In general, the cytoarchitecture of the preoptic area, ventral and dorsal thalamus, epithalamus, and synencephalon resembles the histological pattern of other teleosts. However, the parvocellular preoptic nucleus of sea bass has been subdivided into parvocellular and anteroventral parts for morphological and functional reasons. The hypothalamus of the sea bass seems to differ slightly from that of other teleosts. An elaborated lateral tuberal nucleus, with five subdivisions, and three different nuclei around the lateral recesses were recognized. A medial nucleus of the inferior lobe, which has been reported previously in the perciform Sparus aurata, is also present in the hypothalamus of sea bass but has not been described before in another advanced teleost. The organization of the pretectum and the accessory optic system is essentially similar in sea bass to that described in other perciforms with highly developed vision. The migrated portion of the posterior tuberculum of sea bass appears to differ from this region of the diencephalon in other teleosts. In sea bass, three cell masses that have been described previously only in the perciform Sparus aurata have been assigned to the migrated area of the posterior tuberculum. This study will provide the neuroanatomical basis for future morpho-functional studies to be done in the sea bass brain.     

Population genetics approach to the problem of the nonspecific biological resistance of the human body. I. Statement of the problem and basis for the approach. Distribution parameters of anthropometric markers of normal and ill newborn infants and nurslings

Distributions of two metrical characters-the weight and the body length at birth are considered in several groups of healthy, diseased and dead newborns and infants. Significant differences in statistical parameters of these distributions (mean, standard deviation, skewness and kurtosis) are demonstrated for normal and malformated children. The increased number of children with minimal deviations from the mean values of characters (adaptive norm) is observed among healthy newborns, while in groups of diseased and dead children the frequency of individuals with extreme (especially low) values is increased. The principle of classification of individuals based simultaneously on two characteris is suggested and the problem of "average phenotype" classification by the number of characters is discussed.     

The tardigrades of Emilia (Italy). II. Monte Rondinaio. A multihabitat study on a high altitude valley of the northern Apennines

We investigated a small valley of glacial origin in the northern Apennines (Italy). A multihabitat study was performed on the mosses and lichens on rocks, temporarily submersed mosses, beech litter, grass turf and sediments from pools, ponds and streams. A few species colonized more than one habitat. Several species were typical of high altitudes or latitudes, some were rare, and two, Hypsibius pradellii sp. nov. and Diphascon (Diphascon) secchii sp. nov. , were new to science.     

Biochemistry and genetics of esterase-20 (ES-20), a second trimeric carboxylesterase of the house mouse (mus musculus). II. A unique recombination reveals ES-20 as a hybrid enzyme

A unique recombination is described between (Es-1, Es-6) and (Es-9, Es-22) within gene cluster 1 of the esterase gene region on chromosome 8 of the house mouse. This recombination established the gene order Es-1--Es-6--(Es-9, Es-22)--Got-2. A further 73 recombinations, from a total of 911 backcrosses, had taken place between cluster 1 and cluster 2. A distance between the clusters of 8.01 +/- 0.90% was calculated; the genes within the clusters appeared more tightly linked than previously assumed. ES-20 behaved anomalously following the recombination within cluster 1: homozygous descendants of the recombinant expressed a new form of ES-20. In vitro incubation of purified ES-6A3 and ES-9A generated ES-20A, revealing this esterase to be a hybrid of different cluster 1 gene products, Es-9 and possibly Es-6. This result satisfactorily accounted for the genetic finding, as well as a range of biochemical properties of ES-20.     

A light and electron microscopic study of he heart of a crayfish, Procambarus clarkii (Giraud). II. Fine structure

The adventitia of the crayfish heart is composed of cells that are separated from each other by an intercellular space about 280 Å wide. Desmosomes are present on apposing surfaces of adjacent cells. A basal lamina underlies the adventitia and consists of a dense, amorphous substance that contains numerous fine filaments. The myocardial cells are striated and an external lamina 0.1 μ thick is present on the surface of the plasma membrane. The nuclei and most of the cytoplasm, glycogen and mitochondria are located at the cell periphery. The myofibrils are composed of thick and thin filaments and confined to the core of the cell. A T system and a well-developed SR are present. Elements of these organelles form dyads at levels that correspond to the H bands, and triads at levels that correspond to the Z bands of the peripheral myofibrils. The relationship of the T tubules to the myofibrils is discussed. Locus cells exhibit a unique pattern of intracellular myofibrillar branching. They branch from a region which has a structure similar to the Z band material. The myofibrils radiate outwardly in various directions and form numerous cellular branches which form intercalated discs with adjacent myocardial cells. These discs are more complex than those observed in poikilothermic vertebrates but are simpler than those in mammals. An endocardium is lacking in the crayfish heart but interstitial cells are present in close association with the myocardial cells and neural elements. Terminal nerve processes deeply embedded in the myocardial cells are described.     

Population genetics of sporophytic self-incompatibility in Senecio squalidus L. (Asteraceae) II: a spatial autocorrelation approach to determining mating behaviour in the presence of low S allele diversity

We recently estimated that as few as six S alleles represent the extent of S locus diversity in a British population of the self-incompatible (SI) coloniser Senecio squalidus (Oxford Ragwort). Despite the predicted constraints to mating imposed by such a low number of S alleles, S. squalidus maintains a strong sporophytic self-incompatibility (SSI) system and there is no evidence for a breakdown of SSI or any obvious negative reproductive consequences for this highly successful coloniser. The present paper assesses mating behaviour in an Oxford S. squalidus population through observations of its effect on spatial patterns of genetic diversity and thus the extent to which it is responsible for ameliorating the potentially detrimental reproductive consequences of low S allele diversity in British S. squalidus. A spatial autocorrelation (SA) treatment of S locus and allozyme polymorphism data for four loci indicates that mating events regularly occur at all the distance classes examined from 60 to 480 m throughout the entire sample population. Less SA is observed for S locus data than for allozyme data in accordance with the hypothesis that SSI and low diversity at the S locus are driving these large-scale mating events. The limited population structure at small distances of 60 m and less observed for SA analysis of the Me-2 locus and by F-statistics for all the allozyme data, is evidence of some local relatedness due to limited seed and pollen dispersal in S. squalidus. However, the overall impression of mating dynamics in this S. squalidus population is that of ample potential mating opportunities with many individuals at large population scales, indicating that reproductive success is not seriously affected by few S alleles available for mating interactions.     

Serum methylation levels of TAC1. SEPT9 and EYA4 as diagnostic markers for early colorectal cancers: a pilot study

Abstract

Objective: To identify methylated genes in serum with diagnostic potentials for early colorectal cancer (CRC).

Methods: Serum methylation levels of up to 12 genes were measured in two sets of serum samples with the second set from 26 stage I CRC patients and 26 age/gender-matched controls.

Results: Serum methylation levels of TAC1, SEPT9, and EYA4 were significant discriminants between stage I CRC and healthy controls. Combination of TAC1 and SEPT9 rendered 73.1% sensitivity with 92.3% specificity.

Conclusion: Serum methylation levels of TAC1. SEPT9 and EYA4 may be useful biomarkers for early detection of CRC though a validation study is necessary.