Genic Polymorphism Research Articles

Allelic diversity of flowering-time regulatory gene Hd3a in rice

ABSTRACTFlowering time (FT) of rice (Oryza sativa L.) marks its transition from vegetative to reproductive stage. The FT is controlled by many internal and external factors, where Hd3a is the main florigen regulating FT under short-day conditions. This study was designed to identify the different types of Hd3a promoter and genic haplotypes using 2,638 rice accessions and to detect genetic polymorphisms that are diagnostic to FT. Haplotype analysis was conducted for the promoter and genic region of Hd3a. The FT data were analyzed to reveal associations with genic and promoter polymorphisms. The analysis revealed 12 novel promoter haplotypes and four previously identified genic haplotypes based on 36 polymorphic sites. A high haplotype diversity was reported in both promoter (0.78) and genic (0.67) regions. The 12-bp InDel in the promoter, which was previously defined as diagnostic for FT, could not be generalized to predict FT in the current rice panel. The cis-regulatory elements (CRE) belonging to 32 transcription factor families (TFF) were identified in the promoter, of which four TFF families were related to regulation of reproduction, and two of these families had changed in some accessions because of single nucleotide polymorphisms (SNPs). Of the 36 polymorphic sites used to identify haplotypes, none could be generalized as diagnostic to serve as potential site(s) for marker development. Two SNPs on the Hd3a promoter that caused changes in TFFs could possibly be target sites to study Hd3a expression.

Genetic determinants of acute renal damage risk and prognosis: A systematic review

IntroductionAcute renal damage (ARD) is a frequent syndrome in hospitalized patients. It is well accepted that ARD susceptibility and outcome are related to environmental risk factors and to the patient premorbid status. Recently, host factors have also been recognized as important in ARD predisposition and evolution. ObjectiveTo analyze genetic influences related to the risk and severity of ARD. Data source: MEDLINE search. Selection of studies: articles published in English or Spanish between 1/1/1995 and 31/5/2011, analyzing the association between genic polymorphisms and (a) ARD susceptibility in patients versus healthy controls or within groups of patients; or (b) ARD severity. Exclusion criteria: studies published only in abstract form, case reports or including patients less than 16 years of age, on chronic dialysis or having received a renal transplant. Data extraction: at least one investigator analyzed each manuscript and collected the information using a predefined form. ResultsWe identified 12 relevant studies that included 4835 patients. Eleven genes showed polymorphisms related to ARD susceptibility or severity. They were related to cardiovascular regulation (ACE I/D, eNOS, FNMT and COMT), inflammatory response (TNFα, IL10, IL6, HIP-1α, EPO), oxidative stress (NAPH oxidase) and lipid metabolism (APO E). Only APO E, ACE and AT1 receptor have been analyzed in more than one study. ConclusionARD susceptibility and severity are influenced by genetic factors, which are multiple and involve different physiopathological mechanisms.

Influence of Methylenetetrahydrofolate Reductase C677T, A1298C, and G80A Polymorphisms on the Survival of Pediatric Patients with Acute Lymphoblastic Leukemia

The influence of genic polymorphisms involved in metabolism of chemotherapeutic agents as the methotrexate (MTX) has been studied mainly in acute lymphoblastic leukemia (ALL) of childhood. Advances in treatment may be attributed to identification of prognostic factors added to chemotherapy protocol. The aim of this study was to analyze the association of the C677T, A1298C, and G80A polymorphisms on MTHFR gene and on the overall survival of pediatric patients (n = 126) with lymphoblastic leukemia treated with MTX according to the Brazilian protocol in 187 months. The C677T and G80A polymorphisms were genotyped by PCR-RFLP and A1298C polymorphism by allele-specific PCR. We observed that ALL patients presented rate (dead/alive) of 0.36 for the 677CC genotype, corresponding also to lower overall survival (P = 0.0013); on the other hand, the 677TT genotype showed a better survival (98%). Thus, we believe that patients with 80AA genotype presented a small reduction in MTX plasma level, suggesting that ALL children, carrying the 80AA genotype, showed a high toxicity to MTX (P < 0.0001).

Determinantes genéticos del riesgo y pronóstico del daño renal agudo: una revisión sistemática

Acute renal damage (ARD) is a frequent syndrome in hospitalized patients. It is well accepted that ARD susceptibility and outcome are related to environmental risk factors and to the patient premorbid status. Recently, host factors have also been recognized as important in ARD predisposition and evolution.To analyze genetic influences related to the risk and severity of ARD.MEDLINE search.articles published in English or Spanish between 1/1/1995 and 31/5/2011, analyzing the association between genic polymorphisms and (a) ARD susceptibility in patients versus healthy controls or within groups of patients; or (b) ARD severity.studies published only in abstract form, case reports or including patients less than 16 years of age, on chronic dialysis or having received a renal transplant.at least one investigator analyzed each manuscript and collected the information using a predefined form.We identified 12 relevant studies that included 4835 patients. Eleven genes showed polymorphisms related to ARD susceptibility or severity. They were related to cardiovascular regulation (ACE I/D, eNOS, FNMT and COMT), inflammatory response (TNFα, IL10, IL6, HIP-1α, EPO), oxidative stress (NAPH oxidase) and lipid metabolism (APO E). Only APO E, ACE and AT1 receptor have been analyzed in more than one study.ARD susceptibility and severity is influenced by genetic factors, which are multiple and involve different physiopathological mechanisms.

Tumeurs des voies excrétrices urinaires supérieures sporadiques : identification de l’interaction entre l’exposition aux carcinogènes environnementaux et la susceptibilité génétique des individus

Upper urinary tract urothelial cell carcinomas (UUT UCC) are rare sporadic tumors. Recent epidemiologic and molecular data have shown a singular susceptibility of UUT UCCs for specific risk factors. The main exogenic factors involved in UUT UCCs carcinogenesis remain tobacco and occupational exposure (aromatic amines, polycyclic hydrocarbures and chlored solvents). Enzymatic variants of detoxification system may be responsible of carcinogenesis with these toxics. Tumors induced by phenacetine consumption are decreasing since it was banned in the 1970s. Also, acid aristolochic exposure (Balkan nephropathy, Chinese Herb nephropathy) has been demonstrated to specifically induce UUT UCCs. Familial genic polymorphism of detoxification system would explain geographic distribution in endemic areas. In Taiwan, chronic arsenic exposition would constitute the main risk factor of UUT UCC. However, theses mechanisms of carcinogenesis remain unclear. The knowledge of UUT UCC development mechanisms implying toxic detoxification systems is still incomplete. To date, there is a growing body of evidence supporting that the interaction between individual genetic susceptibilities and environmental toxic exposure is a key to explain carcinogenesis in the majority of sporadic UUT UCC occurrence.

Genic variation in central and marginal populations of Drosophila subobscura.

The genic variability at twenty loci in marginal, submarginal and central populations of Drosophila subobscura has been studied by starch gel electrophoresis. The samples from marginal populations orginate from Finland, the submarginal ones from Sweden and Denmark, whereas flies collected from France and northeastern Italy are taken to represent central populations. The average degrees of genic polymorphism are undifferentiated over the distribution area of D. subobscura. Most loci have fairly uniform allele frequencies in all populations. Local differences have been found at six loci. These fluctuations represent adaptations to local environmental differences.

Absence of genic polymorphism in a northern population of the house sparrow, Passer domesticus

(Received April 7, 1983) The house sparrow is a classical object in studies of adaptive morphological variation. E.g., close linkage of character variation with environmental variation, rapid evolution of size and other var- iables in relatively few generations, and accentuated effect of winter mortality on sexual size dimorphism have been documented in this bird

Polymorphism of Old Kladruber horses, a surviving but endangered baroque breed.

Analysis of MHC class I and class II polymorphism, as well as data from other polymorphic systems (non-MHC lymphocyte alloantigen, blood groups systems, biochemical polymorphisms and microsatellite loci), was used to characterize the extent and distribution of the genic polymorphism of Kladruber horses. A breed-characteristic distribution of the MHC polymorphism was found. The repertoire of defined MHC class I specificities was restricted, especially in the grey subpopulation and in stallions, but a high frequency of blanks suggests the possible existence of undetected specificities. Despite the small population size and a relatively high degree of inbreeding, high heterozygosity in MHC haplotypes has been conserved. The extent of polymorphism and the degree of heterozygosity in other loci were also relatively high. A comparison of the two existing subpopulations, grey and black, at all the loci tested, including RAPD markers, characterized them as genetically distinct, although clearly related. The genetic distances between them were of the same order of magnitude as between distinct breeds. The results may be useful in defining short-term and long-term breeding policy within the breed and for further studies of associations with disease and other traits.

Strong habitat selection and the development of population structure in a mosquito

Remarkably simple and regular patterns of genic variation for two electrophoretically assayed loci are presented against a background of strong habitat selection, population isolation, and population structuring in the pitcher-plant mosquitoWyeomyia smithii. The genic variation assessed thus far comes from 29 local populations, all but one of which lie within the glaciated region of North America. Although the conclusions drawn from these patterns are still quite tentative, it appears that the fact that the same higher frequency electromorphs occurred everywhere for both loci may be due more to selection than drift. Drift or selection, acting alone or in concert may be responsible for the almost complete absence of electromorphs of intermediate frequency. A weak association was found between the two-locus genic variation and the well-studied diapause-development time variation in this species. It is suggested that a Wrightian interaction system and fluctuating-stabilizing selection might account for maintenance of the genic level polymorphism. The observations reported are circumstantially in accord with Wright's shifting balance process of evolution. Future studies in the older parts of the species range will put these hypotheses to a strong test.

Reproductive Cycles in the Mesquite Lizard Sceloporus grammicus

The reproductive cycle of a population of Sceloporus grammicus in the Michilia Biosphere Reserve, Durango, Mexico, was determined through the autopsy of 117 M6 and 125 QQ. Vitellogenesis starts in mid August and ends in early November. Ovulation occurs in December and parturition during mid May. Males are reproductively active from early November to early December, exhibiting a marked decline in gonadal activity from January to May. Maximum testic- ular and ovarian activities occur at the same time. Reproductive characteristics of this population are compared with another poulation of the same species from a similar elevation but from a southern locality previously studied by other authors. We have found profound differences for both sexes between the two populations. Studies of repro- ductive patterns for intermediate populations are needed. Sceloporus grammicus Wiegmann is a small viviparous lizard (53-72 mm SVL) distributed throughout most of Mexico from north of the Tehuantepec Isthmus to Southern Texas. Along this range it is found in several habitats, from sea level to high mountain conditions (>4000 m). This species exhibits an amazing array of differences in color pattern as well as extensive variation in morphometric and meristic character- istics. Its genic polymorphism and het- erozygosity values are among the high- est known for lizards (Hall and Selander, 1973; Sites, 1980). Although Sceloporus grammicus is ex- tremely common in many sites, some- times being a dominant vertebrate in numbers, there is very little informa- tion regarding its natural history (Ax- tell and Axtell, 1970; Guillette and Cas-

Genic Variability, Dispersal, and Differentiation in Two Species of Ophiuroids from Southern California

Genic Variability, Dispersal, and Differentiation in Two Species of Ophiuroids from Southern California

MDH-polymorphism in Drosophila subobscura: I. Selection and hitch-hiking in laboratory populations

The interrelation of genic polymorphism at the Malate dehydrogenase (Mdh)-locus and chromosomal polymorphism for superimposed gene arrangements was studied in 5 experimental populations of Drosophila subobscura. It could be shown that chromosomal polymorphism is maintained by balancing selection in favour of the heterozygotes. In contrast, selection at the Mdh-locus itself seems to be of minor importance. The changes of frequency observed for the Mdh-alleles are most probably due to hitch-hiking on the gene blocks enclosed by the chromosomal structures or to selection for tightly linked genes rather than to fitness differences between Mdh-genotypes. The results may be considered as a model for the situation found in natural populations of D. subobscura.

Genetic Variation and Progressive Evolution

The present theory offers a unified solution to three closely related evolutionary problems. (1) Why does an evolving population explore only a small fraction of the accessible pathways in genotype space? (2) Conventional ideas about genetic variation suggest that major adaptive shifts, which involve large numbers of separate but functionally related genetic changes, have vanishingly small probabilities of occurrence and require long periods of time. Yet the fossil record indicates that such shifts are neither slow nor uncommon. (3) Studies in comparative morphology and comparative embryology indicate that evolution is a process of hierarchic construction. How is the principle of hierarchic construction related to the basic postulates of evolutionary theory? According to the theory elaborated in this paper, the genomes of both unicellular and multicellular organisms contain two functionally distinct systems of genes: an a system, which encodes a program for the organism's development and which includes regulatory genes and other "modifiers" as well as structural genes; and a β system, which encodes a strategy for adaptive variability and whose elements regulate the rates of genetic recombination and of genic and chromosomal mutations. Corresponding to these two systems are two classes of adaptations: a adaptations, which enhance the fitness of their possessors, and β adaptations, which increase the expectation of fitness in the descendants of their possessors. Sexual reproduction is the most familiar example of a β adaptation. It is noteworthy that the most primitive known form of sexuality, that found among bacteria, is characterized by genetic mechanisms serving to regulate genetic recombination in precisely the manner postulated here for β genes. The β system serves to direct evolutionary flows in genotype space into potentially adaptive channels. It also serves to stabilize and buffer highly adapted genetic structures against the potentially disruptive effects of accidental variations. At the genetic level of description, a major adaptive shift corresponds to the ascent of a fitness peak in a multidimensional subspace of genotype space. The β system serves to focus evolutionary flow in this subspace in the direction of steepest ascent, thereby ensuring rapid and coordinated evolution of the genetic systems involved. (A mathematical framework that should make it possible to construct numerical models of the evolutionary process just described is given by Layzer [1978a].) The principle of hierarchic construction emerges as a natural consequence of selection-regulated genetic variation. Hierarchic units are defined by their covariability (or costability). The "otherwise inexplicable tendency of organisms to adopt ever more complicated solutions to the problem of remaining alive" (Medawar 1967, pp. 99-100) results from the action (and progressive elaboration) of a genetic system that promotes just those kinds of genetic variation that result in the growth of functionally hierarchic genetic systems. The present theory also throws light on several specific evolutionary problems, including the interpretation of genic polymorphism, the variability of evolutionary rates inferred from the fossil record, the evolution of "pseudoexogenous" and "trivial" adaptation, and the problem of speciation. Applications to the evolution of social behavior are discussed elsewhere (Layzer 1978b).

Systematic Status of Kangaroo Mice, Genus Microdipodops: Morphometric, Chromosomal, and Protein Analyses

The systematic status of Microdipodops megacephalus and M. pallidus is investigated at the genic, karyotypic, and morphologic levels at a purported hybrid zone. Instances of hybridization are shown to be either nonexistent or present at extremely low levels (≼0.6%), and full specific status of the two taxa is affirmed. Amounts of genic variability and polymorphism are approximately equal for the species (H = 0.064) and fall well within the range observed for other vertebrate species. Estimates of the timing of the speciation event, based upon allozymic data, range from 1.2 to 6 million years before present. Possible means of ecological separation of the two sibling species in sympatry are suggested.

SELECTION DIFFERENTIALS AND SELECTION COEFFICIENTS

Proof is offered that s approximately ig for all forms of selection where fitness is a nondecreasing function of a normally distributed phenotype (called fitness potential); s is selection coefficient, i is standard selection differential, and g is standard differential effect of a locus genotype.Evidence is presented that the cost of selection does not limit genic polymorphism; that truncation selection is not necessary for high cost-efficiency; and that opposing directions of selection in a heterogeneous environment do not reduce cost-efficiency critically.

Conservation and chromosomal localization of DNA satellites in balenopterid whales.

DNA satellites were isolated from three balenopterid species, viz. the minke, sei, and fine whales. In each of them at least two DNA satellites were recognizable with buoyant densities in neutral CsCl of rho = 1.702/1.703 and rho = 1.710/1;711, respectively. cRNAs from each satellite group were used for filter and in situ hybridisations. Homo-and heterologous DNA-cRNA hybrids within each satellite group yielded virtually identical melting curve profiles showing conservation of at least a considerable part of the DNA satellite sequences. There was no evident sequence homology between the rho = 1.702/1.703 and the rho = 1.710/1;711 satellites by filter hybridisation.--The in situ hybridisation showed that in each species the rho = 1.702/1.703 satellite was located in centromeric-paracentromeric C-bands in a few pairs, whereas the rho = 1.710/1.711 satellite was located in terminal C-bands throughout the karyotypes.--The data on the whale DNA satellites indicate that the quantitative evolution of the sateliite DNA sequences preceded species divergence of the balenopterids and that the satellite sequences have remained relatively unaltered since the divergence took place. The function of satellite DNA is considered to imply the introduction of both chromosomal and genic polymorphisms and thus being of great importance in speciation, Based upon these concepts a model is postulated for the function of satellite DNA. According to this model at meiotic pairing euchromatinheterochromatin overlapping between homologous chromosomes is considered to be of a general occurrence. This overlapping is presumed to be accentuated by the size heteromorphism frequently observed between homologous heterochromatic segments (C-bands). In the region of such euchromatinheterochromatin overlapping, cross-over would be excluded. The overlapping is suggested to be rectified progresssively in the chromosome arms, leaving unaffected crossing-over distant to the euchromatin-heterochromatin junctions. The consequence of this will be that genes in the proximity of the junctions are collectively inherited and selected, whereas genes distant to the the heterochromatin will be independently assorted and selected.

GENIC HETEROGENEITY AT TWO ALCOHOL DEHYDROGENASE LOCI IN DROSOPHILA PSEUDOOBSCURA AND DROSOPHILA PERSIMILIS

A sequential electrophoretic survey of the second chromosome loci, alcohol dehydrogenase-6 (Adh-6) and octanol dehydrogenase ( Odh), was performed on 147 isochromosomal lines of Drosophila pseudoobscura and 60 lines of its sibling species, D. persimilis. Gels run with a variety of acrylamide concentrations and buffer pH's revealed the presence of 18 alleles of Adh-6 in the two species, where only eight had been previously detected by conventional electrophoretic methods. Only two alleles were added with our techniques to the previous total of nine in both species at the largely monomorphic Odh locus. Both enzymes show a predominance of one allele, with the other variants being fairly rare. There was no evidence of increased genetic divergence between the two species, but we found a striking increase in differentiation of Adh-6 alleles between the main body of D. pseudoobscura populations and the conspecific isolate from Bogotá, Colombia. These results are compared with our previous surveys of xanthine dehydrogenase in these species and discussed in reference to theories of genic polymorphism.

EVOLUTION AT THE α-GPDH LOCUS IN DROSOPHILIDAE.

The study of enzyme polymorphism in natural populations of different species of Drosophila has lately been one of the main subjects of population genetics (Ayala and Powell, 1972; Lakovaara and Saura, 1971; Lewontin and Hubby, 1966; O'Brien and MacIntyre, 1969; Prakash, 1973a, b; Richmond, 1972; Saura, 1974; Saura et al., 1973; Yang et al., 1972; and others). These Drosophila studies constitute by far the most extensive data now available on the genic polymorphism in a single genus. The general result of the studies on the genic polymorphism in natural populations of Drosophila has been the detection of a rather constant degree of heterozygosity and slightly fluctuating allele frequencies from population to population of a given species. Most investigators doing experimental work on natural populations hold that the electrophoretic variants detected by them are subject to natural selection, i.e. the polymorphisms at enzyme loci are maintained by different forms of balancing selection (e.g. the studies cited above). Gillespie and Kojima (1968) and Kojima et al. (1970) first suggested that physiological function of enzymes may be correlated with the degree of polymorphism at the corresponding loci. The argument is important-in fact, it may well become far more important and straightforward in proving or disproving the significance of selection than the often frustrating efforts to prove conclusively anything concerning e.g. the effects of migration and environment on the genetic makeup of populations. The hypothesis of Gillespie and Kojima states that glucose metabolizing enzymes are in general less variable than other enzymes. This seems to hold true for Droso phila, but it need not be universally true. Data from vertebrates and other insects do not always agree (Frydenberg and Simonsen, 1973; Lokki et al., 1975). Pooling of data froni different organisms may easily lead to confusing results. In evolutionary studies of proteins, gel electrophoresis has a single advantage over the more accurate amino acid sequencing. By electrophoresis it is possible to observe with little effort the variability in thousands of individuals. In this study we utilize data collected by screening hundreds of thousands of flies belonging to the family Drosophilidae for electrophoretically detectable variants of a-glycerophosphate dehydrogenase. This enzyme (a-GPDH, L-glycerol-3-phosphate NAD oxidoreductase, E C 1.1.1.8.) is coded by the aglycerophosphate dehydrogenase (aGPDH) locus. The most important function of aGPDH in the metabolism of an adult fly is its function in the flight muscle, where the soluble, NAD-dependent enzyme together with a mitochondrial, particle-bound and flavine-linked oxidase comprises the so-called a-glycerophosphate cycle (e.g. Hansford and Sacktor, 1971). This cycle produces energy for flight through electron transfer in the mitochondria. The two other functions of a-GPDH are maintenance of the balance between oxidized and reduced NAD in the cytoplasm for glycolysis, and supplying glycerophosphate for synthesis of lipids (e.g. O'Brien and MacIntyre, 1972a, b).

Electrophoretic variation in Escherichia coli from natural sources.

At each of five loci in 829 Escherichia coli clones from 156 samples from diverse natural sources, electrophoretic analysis reveals a prominent mobility class (frequency over 0.70) and 2 to 11 distinct mobility classes at lower frequencies. The frequency distribution of the classes argues against the importance of neutral mutations in allozymic variation. Heterosis is not the universal cause of genic polymorphism.

Protein Variation and Systematics in Kangaroo Rats (Genus Dipodomys)

Johnson, Walter E. and Robert K. Selander (Department of Zoology, The University of Texas, Austin, Texas 78712) 1971. Protein variation and systematics in kangaroo rats (genus Dipodomys). Syst. Zool. 20:377-405.-Electrophoretically demonstrable genetic variation in 11 enzymes and six non-enzymatic proteins encoded by 18 loci was analyzed in 1208 specimens of 11 species of kangaroo rats (Dipodomys) from the westem United States and in a related heteromyid, the pocket-mouse Perognathus hispidus. Most of the 17 proteins studied exhibit both polymorphic and interspecific variation, but protein-I is invariable; and protein-2, protein-3, and hemoglobin are interspecifically variable although not polymorphic in any species. Except for Hb-1 (hemoglobin) and Trf-1 (transferrin), there is at each locus one allele which tends to predominate in all species of Dipodomys. The maximum number of alleles detected at a single locus in a population was three. Species of Dipodomys are, on the average, less variable genetically than other organisms for which estimates of levels of polymorphism and heterozygosity are available. An average of 7.9% of loci are polymorphic per population, and mean heterozygosity is 2.1%O. Only four species are genetically as variable as rodents of the genera Mus and Peromyscus. Genic variability is uniform within species and is not correlated among species with extent of geographic range or degree of morphological specialization. Possible relationships between degree of genetic variability and ecological amplitude or niche width are discussed. Significant regional heterogeneity in allele frequencies was demonstrated at most polymorphic loci in species that were relatively well sampled. Because geographic variation is limited, useful estimates of frequencies of the major alleles at loci in a species can be obtained from a small number of samples taken anywhere within the range. Coefficients of genetic similarity between conspecific populations invariably exceed 0.90. For interspecific comparisons, coefficients range from 0.31 to 0.89, with a mean of 0.61. On the average, species of Dipodomys are genetically more similar than are non-sibling species of Drosophila or Anolis. The pattem of relationships among species of Dipodomys indicated by genetic analysis differs significantly from those derived by Setzer, Lidicker, and others on morphological grounds but is similar to that provided by Stock's recent analysis of karyotypic variation in the genus. [Protein variation; electrophoresis; Dipodomys.] A fundamental tenet of evolutionary theory is that race formation and speciation occur by the conversion of genetic variation within populations to variation among populations (Lewontin, 1967). For this reason, evolutionists have long sought to determine the extent of genetic variation in local populations, among geographic populations, and among closely related species (Dobzhansky, 1970; Mayr, 1970). With the recent development of electrophoretic techniques for demonstrating allelic variation at genetic loci controlling the structure of enzymes and other proteins, it has become possible to estimate several critical parameters of genetic variation in natural populations, working on the assumption that the structural genes sampled are representative of the genome (Hubby and Lewontin, 1966; Lewontin and Hubby, 1966; Harris, 1970; Selander and Johnson, 1971). The few available estimates of degree of genic polymorphism in populations indicate that there is a considerable range of variation, even among congeneric species (see review in Selander et al., 1970) and among populations of the same species (Prakash et al., 1969; Selander, Hunt, and Yang, 1969; Selander et al., 1971). Studies of geographic variation in allele frequencies and of semi-species and sibling species suggest that the amount of genomic modification