Genetic nets and dissipative structures: An algebraic approach

Genetic nets represent an attempt to model genome structure. Depending on the interaction dynamics assumed, they can constitute highly non-linear chemical systems having multiple steady states; hence their relevance to the theory of dissipative structures. Their typical size and possible complexity makes it difficult to study them by means of customary analytical techniques based on differential equations. We have therefore considered an algebraic approach derived from regarding the nets as finite-state automata. This view has revealed a surprisingly rich algebraic structure which can be used to investigate problems concerned with the relation between biological structure and function. This algebraic structure is described with particular reference to the genetic nets of Tsanev and Sendov. Proceedings article from the Dissipative Structures Section of the Tenth Symposium on Biomathematics and Computer Science in the Life Sciences, University of Texas, Houston. March 29–31, 1973. Symposium Chairman: Stuart O. Zimmerman. Session Chairman and Proceedings Editors: Charles Walter and Hugo M. Martinez.     

Blood group frequencies in Romania: microregional and ethnic differences

This study is based on the results of the blood group typing (AB0, MN, RH: D/d) of two samples from Romania and on literature data. The 40 population samples used are scattered on the today's territory of Romania. Some data refer to more or less endogamous villages or groups of villages which belong to the same marriage area, some data refer to towns with admixed populations. Samples of nine ethnic minorities have been included in the study. The results have been discussed on the basis of the historical and geographical background.     

Genetic and linguistic coevolution in Northern Island Melanesia

Recent studies have detailed a remarkable degree of genetic and linguistic diversity in Northern Island Melanesia. Here we utilize that diversity to examine two models of genetic and linguistic coevolution. The first model predicts that genetic and linguistic correspondences formed following population splits and isolation at the time of early range expansions into the region. The second is analogous to the genetic model of isolation by distance, and it predicts that genetic and linguistic correspondences formed through continuing genetic and linguistic exchange between neighboring populations. We tested the predictions of the two models by comparing observed and simulated patterns of genetic variation, genetic and linguistic trees, and matrices of genetic, linguistic, and geographic distances. The data consist of 751 autosomal microsatellites and 108 structural linguistic features collected from 33 Northern Island Melanesian populations. The results of the tests indicate that linguistic and genetic exchange have erased any evidence of a splitting and isolation process that might have occurred early in the settlement history of the region. The correlation patterns are also inconsistent with the predictions of the isolation by distance coevolutionary process in the larger Northern Island Melanesian region, but there is strong evidence for the process in the rugged interior of the largest island in the region (New Britain). There we found some of the strongest recorded correlations between genetic, linguistic, and geographic distances. We also found that, throughout the region, linguistic features have generally been less likely to diffuse across population boundaries than genes. The results from our study, based on exceptionally fine-grained data, show that local genetic and linguistic exchange are likely to obscure evidence of the early history of a region, and that language barriers do not particularly hinder genetic exchange. In contrast, global patterns may emphasize more ancient demographic events, including population splits associated with the early colonization of major world regions.     

One-sided sequential stopping boundaries for clinical trials: a decision-theoretic approach

We address one-sided stopping rules for clinical trials, or more generally, drug development programs, from a decision-theoretic point of view. If efficacy results are sufficiently negative then the trial will be stopped. But regardless of how positive the efficacy results are, the trial will continue in order to demonstrate safety. We show how sequential decisions should be made by a pharmaceutical company attempting to maximize its expected profits.     

Genetic changes across language boundaries in Europe

By means of three different methods we investigated whether 59 allele frequencies and ten cranial variables show increased change at 29 language-family boundaries in Europe. The quadrat-variance method compares variances of map quadrats crossed by language-family boundaries to variances of quadrats that are not crossed. The rate-of-change method examines the directional derivative of surfaces of the variables perpendicular to a language-family boundary and compares these derivatives to the same quantities obtained by randomly placing the language boundaries on the map of Europe. The difference method tests whether these variables differ more across language-family boundaries than across randomly placed boundaries. These special data-analytic techniques had to be developed to avoid the problem of spatial autocorrelation of both language and biological data. All three methods indicate increased genetic change at language-family boundaries. Clearer and more pronounced results are obtained by the first two methods than by the difference method. Thirteen language-family boundaries show significant gene frequency change by at least one of the methods. Changes are more marked in gene frequencies than in cranial variables. Different allele frequencies mark the increased change at different language boundaries. A model, based on the known history of each language-family boundary, was constructed to predict whether given boundaries should exhibit increased genetic change. The model is in good agreement with the observed results.     

Genetic structures in the population of Veneto.

The genetic structures of the population residing in the provinces of Venice and Rovigo in the Veneto region at the north of the Po delta in Italy was studied in 1,210 individuals residing in 18 sampling areas, using the phenotype and gene frequencies of 7 red cell enzymes: acid phosphatase (ACP1), esterase D (ESD), glyoxalase I (GLOI), glutamic-pyruvic transaminase (GPT), 6-phosphogluconate dehydrogenase (6-PGD), phosphoglucomutase 1 (PGM1), and phosphoglycollate phosphatase (PGP). For the analysis of the distributions of phenotype and gene frequencies, standardized variance and kinship profiles were used. It was found that the genetic differentiation within each province is low, and that only two systems, GPT and PGP, are significantly different between the two provinces. The samples studied seem to belong to a mainly homogeneous population.     

Genetic and linguistic affinities between human populations in Eurasia and West Africa

This study examines the relationship between genetic distance and linguistic affiliation for five regional sets of populations from Eurasia and West Africa. Human genetic and linguistic diversity have been proposed to be generally correlated, either through a direct link, whereby linguistic and genetic affiliations reflect the same past population processes, or an indirect one, where the evolution of the two types of diversity is independent but conditioned by the same geographical factors. By controlling for proximity, indirect correlations due to common geography are eliminated, and any residual relationships found are likely to reflect common linguistic-genetic processes. Clear relationships between genetic distances and linguistic relatedness are detectable in Europe and East and Central Asia, but not in the Middle East, Southeast Asia, or West Africa. We suggest that linguistic and genetic affiliations will only be correlated under specific conditions, such as where there have been large-scale demic diffusions in the last few thousand years, and relative sedentism in the subsequent period.     

Biochemical and genetic properties of oligomeric structures: a general approach

The oligomers constituted by association of different subunits can exist under multiple forms. In the case of the genetically variable proteins, such a multiplicity leads to numerous questions (i) on the enumerations: what is the number of active forms when a given subunit can make the oligomer inactive, or when the subunits are encoded by s alleles; (ii) on the subunit effects on biochemical properties: how to estimate these effects, are they equal, are there interactions between subunits, etc. Theoretical methods for the study of such oligomeric structures are developed, which mainly rely on linear model techniques. Peculiar properties examined are Vmax and Km, but also the quantities of the various oligomers, which depend on their association law. This approach is extended to the oligomers composed of different sets of subunits, as are for example some enzymes. These aspects are discussed from numerous bibliographic examples, with special reference to molecular interactions (protein complementation or molecular heterosis). Otherwise the genetic application of this theoretical approach is presented: it is possible to consider a genotype as an oligomer of alleles, and thus to study their effects and their interactions, in the one-locus case as well as in the several-loci case. The relevance of this generalization is discussed in connection with two other concepts, the "sequence space" used in molecular evolution and the regression of the genotypic values on the number of alleles used in quantitative genetics.     

Genetic disorders of the skeleton: a developmental approach

Although disorders of the skeleton are individually rare, they are of clinical relevance because of their overall frequency. Many attempts have been made in the past to identify disease groups in order to facilitate diagnosis and to draw conclusions about possible underlying pathomechanisms. Traditionally, skeletal disorders have been subdivided into dysostoses, defined as malformations of individual bones or groups of bones, and osteochondrodysplasias, defined as developmental disorders of chondro-osseous tissue. In light of the recent advances in molecular genetics, however, many phenotypically similar skeletal diseases comprising the classical categories turned out not to be based on defects in common genes or physiological pathways. In this article, we present a classification based on a combination of molecular pathology and embryology, taking into account the importance of development for the understanding of bone diseases.     

Genetic variation within two linguistic Amerindian groups: relationship to geography and population size

Nine Carib and eight Tupi groups were studied for a minimum of eight common polymorphic systems and compared in terms of genetic distances using the methods of Nei and Edwards. Two levels of genetic information were distinguished, one with a maximum of 20 loci and another with a maximum of 12 loci considered. The dendrograms produced consistent, reproducible results, independent of the method used, when a minimum of ten polymorphic systems were included in the analysis. Irrespective of the number of systems or the method used, the Tupi showed two to three times higher average interpopulation genetic distances than the Carib groups, which may be due to their lower average population sizes, allowing for the action of genetic drift and/or founder effects, as these two sets of populations do not differ significantly in geographic range, years of contact with non-Indians, or degree of acculturation.     

Genetic improvement for phosphorus efficiency in soybean: a radical approach

Background

Low phosphorus (P) availability is a major constraint to soybean growth and production. Developing P-efficient soybean varieties that can efficiently utilize native P and added P in the soils would be a sustainable and economical approach to soybean production.

Scope

This review summarizes the possible mechanisms for P efficiency and genetic strategies to improve P efficiency in soybean with examples from several case studies. It also highlights potential obstacles and depicts future perspectives in ‘root breeding’.

Conclusions

This review provides new insights into the mechanisms of P efficiency and breeding strategies for this trait in soybean. Root biology is a new frontier of plant biology. Substantial efforts are now focusing on increasing soybean P efficiency through ‘root breeding’. To advance this area, additional collaborations between plant breeders and physiologists, as well as applied and theoretical research are needed to develop more soybean varieties with enhanced P efficiency through root modification, which might contribute to reduced use of P fertilizers, expanding agriculture on low-P soils, and achieving more sustainable agriculture.     

Stochastic modeling of RNA pseudoknotted structures: a grammatical approach

MOTIVATION: Modeling RNA pseudoknotted structures remains challenging. Methods have previously been developed to model RNA stem-loops successfully using stochastic context-free grammars (SCFG) adapted from computational linguistics; however, the additional complexity of pseudoknots has made modeling them more difficult. Formally a context-sensitive grammar is required, which would impose a large increase in complexity. RESULTS: We introduce a new grammar modeling approach for RNA pseudoknotted structures based on parallel communicating grammar systems (PCGS). Our new approach can specify pseudoknotted structures, while avoiding context-sensitive rules, using a single CFG synchronized with a number of regular grammars. Technically, the stochastic version of the grammar model can be as simple as an SCFG. As with SCFG, the new approach permits automatic generation of a single-RNA structure prediction algorithm for each specified pseudoknotted structure model. This approach also makes it possible to develop full probabilistic models of pseudoknotted structures to allow the prediction of consensus structures by comparative analysis and structural homology recognition in database searches.     

Genetic epidemiology of congenital muscular dystrophy in a sample from north-east Italy

Congenital muscular dystrophy (CMD) is a heterogenous disease with autosomic recessive transmission. In an epidemiological study in four provinces of Veneto (region of 2586830 inhabitants in north-east Italy), the recorded incidence rate for the period 1979–1993 was 4.65 x 10^–5; the prevalence rate in the year 1993 was 6.8 × 10^–6. The incidence and the prevalence rates that we have obtained during the course of our investigation represent the first estimates for CMD in Europe and show that this myopathy is among the most frequent neuromuscular diseases with autosomic recessive transmission.     

Genetic survey on a reed-bed in Central Italy showing early die-back symptoms

Phragmites australis die-back is a well known phenomenon in Central Europe and rather recently observed also in some Mediterranean wetlands. In this study we analyze the genetic structure of a reed-bed in a protected wetland in N-W Tuscany (Italy) recently showing some clear symptoms of die-back, in particular the clumped growth-form, searching for any possible relationships with the ecological condition or the health status of common reed stands. After a diachronic analysis of vegetation maps (from 1988 to 2013) and a field survey, we have sampled four temporarily emerged and four permanent submerged reed stands, being the submersion regime a crucial trigger of reed die-back. Aquatic plots showed two clear conditions, with the presence of clumped and non-clumped stands. Emerged stands have been sampled in areas showing temporarily stable, increasing and decreasing reed-bed surface. In order to investigate the genetic structure of the population, the AFLP technique was applied on 69 individuals. The total reedbed surface showed a decrease in the observed time, partly due to the human activities and partly attributable to the RDBS. In several areas of the Lake the reed-bed appeared clumped and fragmented. The genetic analysis put in evidence a rather high level of genetic diversity, compared to the results of previous international studies on other populations of the same species. No significant differences between temporarily and permanently submerged stands were found. The major portion of genetic variation appeared within sampling sites rather than between sampling sites, indicating the absence of isolation between the different reed stands of the lake and a negligible role of genetic diversity in the occurrence of die-back symptoms.     

Species boundaries and phylogeography of the "Euscorpius carpathicus complex" (Scorpiones: Euscorpiidae) in Italy

Euscorpius tergestinus (C.L. Koch, 1837), Euscorpius concinnus (C.L. Koch, 1837) and Euscorpius sicanus (C.L. Koch, 1837), three presumed closely related species belonging to the "carpathicus group", occur in the Italian peninsula with a largely parapatric distribution and some zones of range overlap. These areas of sympatry represent interesting opportunities to investigate species boundaries in natural populations. Here we report on a study exploring genetic variation in sympatric populations of the three species from central Tuscany. Additional collecting sites, from different localities across Italy, were also included in the analysis in order to explore the phylogeographic structure of the group. Species boundaries and evolutionary relationships were examined by sequence comparison of mitochondrial 16S rRNA and nuclear ITS-1 rRNA gene fragments. DNA sequence data show no evidence of genetic introgression between different evolutionary lineages from the area of range overlap, suggesting the absence of either past or ongoing inter-specific gene flow. It is therefore probable that reproductive barriers exist, preventing gene pools from amalgamating. Furthermore, our results support the recent morphological distinction of E. tergestinus, as traditionally classified, into two different species: E. tergestinus and E. concinnus. Both mitochondrial and nuclear sequence data clearly indicate that the two taxa represent well-supported and deeply divergent lineages. Euscorpius sicanus seems to represent a monophyletic taxon, but the high genetic variability observed within this taxon calls for future investigation. The present distribution patterns across the Italian peninsula were mainly interpreted as the consequence of climatic oscillations.     

Genetic predisposition to left ventricular dysfunction: a multigenic and multi-analytical approach

Background

Left ventricular dysfunction (LVD) is a complex, multifactorial condition, caused by mechanical, neurohormonal, and genetic factors. We have previously observed association of renin–angiotensin–aldosterone system (RAAS), matrix metalloproteinases (MMPs) and inflammatory pathway genes with LVD. Therefore the present study was undertaken to identify the combination of genetic variants and their possible interactions contributing towards genetic susceptibility to LVD in the background of coronary artery disease (CAD).

Methods and results

The study included 230 healthy controls and 510 consecutive patients with angiographically confirmed CAD. Among them, 162 with reduced left ventricle ejection fraction (LVEF ≤ 45%) were categorized as having LVD. We analyzed 11 polymorphisms of RAAS, MMPs and inflammatory pathways. Single locus analysis showed that AT1 A1166C (p value < 0.001; OR = 3.67), MMP9 R668Q (p value = 0.007; OR = 3.48) and NFKB1-94 ATTG ins/del (p value = 0.013; OR = 2.01) polymorphisms were independently associated with LVD when compared with both non-LVD patients and healthy controls. High-order gene–gene interaction analysis, using classification and regression tree (CART) and multifactor dimensionality reduction (MDR) revealed that AT1 A1166C and NFKB1-94 ATTG ins/del polymorphisms jointly increased the risk of LVD to great extent (p-value = 0.001; OR = 8.55) and best four-factor interaction model consisted of AT1 A1166C, MMP7 A-181G, MMP9 R668Q and NFKB1-94 ATTG ins/del polymorphisms with testing accuracy of 0.566 and cross validation consistency (CVC) = 9/10 (permutation p < 0.001) showed increased risk for LVD respectively.

Conclusion

AT1 A1166C independently and in combination with MMP9 R668Q and NFKB1-94 ATTG ins/del polymorphisms plays important role in conferring genetic susceptibility to LVD in CAD patients.