ANNALS OF HUMAN GENETICS, Issue 6 2003
Qihua Tan
Summary In this paper, we apply logistic regression models to measure genetic association with human survival for highly polymorphic and pleiotropic genes. By modelling genotype frequency as a function of age, we introduce a logistic regression model with polytomous responses to handle the polymorphic situation. Genotype and allele-based parameterization can be used to investigate the modes of gene action and to reduce the number of parameters, so that the power is increased while the amount of multiple testing minimized. A binomial logistic regression model with fractional polynomials is used to capture the age-dependent or antagonistic pleiotropic effects. The models are applied to HFE genotype data to assess the effects on human longevity by different alleles and to detect if an age-dependent effect exists. Application has shown that these methods can serve as useful tools in searching for important gene variations that contribute to human aging and longevity. [source]

Interleukin-1 receptor antagonist and tumour necrosis factor-alpha gene polymorphisms in Turkish patients with allergic contact dermatitis

CONTACT DERMATITIS, Issue 2 2009
Ilgen Ertam
Background: It has been shown that the family of interleukin-1 receptor antagonist (IL-1 RA) and tumour necrosis factor-alpha (TNF,) genes are polymorphic and related to some inflammatory diseases. Allergic contact dermatitis is the classic presentation of delayed-type hypersensitivity responses to exogenous agents. A number of genes playing role in inflammatory response may be associated with allergic contact dermatitis. Objectives: To investigate whether there is an association between IL-1RA and TNF, gene polymorphisms and allergic contact dermatitis in Turkish patients with allergic contact dermatitis. Methods: This study was performed by the collaboration of Departments of Dermatology and Medical Genetics, Ege University, Faculty of Medicine. A total of 50 patients (31 females and 19 males) with allergic contact dermatitis, and 100 age- and sex-matched controls (58 females and 42 males) were included in the study. IL-1RA Variable Number of Tandem Repeats (VNTR) polymorphism in intron 2 and TNF,-308G-A polymorphism were genotyped by using polymerase chain reaction and agarose gel electrophoresis. Results: The frequency of IL-1RA 1/2 (48%) genotype was significantly higher (P = 0.002) in patient group than that is found in control group (22%). The frequency of TNF, (TNF G-308A) G/G genotype was significantly higher in patient group (68%) than that is found in control group (31%) (P = 0.008). Conclusions: Our findings suggest that TNF, (G/G) gene polymorphism may play role in susceptibility to allergic contact dermatitis in Turkish patients. [source]

Phenotypic plasticity, polymorphism and phylogeny within placoderms

ACTA ZOOLOGICA, Issue 2009
K. Trinajstic
Abstract Intraspecies variation, polymorphism and asymmetric traits are observed within two families of Arthrodira, the Incisoscutidae and Camuropiscidae, from the Gogo Formation in northern Western Australia. Individual plates of the head and trunk shield show considerable variation between individuals. Plates that show the greatest degree polymorphic traits are the rostral (R), marginal (M), submarginal (SM), preorbital (PrO), anterior dorsolateral, anterior median ventral (AMV) and posterior ventrolateral (PVL) plates. The paths of the sensory line canals are the most variable feature and the dermal plates of the cheek show the greatest asymmetry. It is apparent that if anatomical data in arthrodires are to be interpreted with greater precision, detailed knowledge of intraspecies variation, polymorphic and asymmetric traits is essential. How these variables are treated in cladistic analysis is also critical. Here multistate characters were coded differently in five discrete analyses, each analysis yielding a different number of trees and relationships. It was concluded that including and coding for multistate characters gave the most robust tree. In addition, further morphological characters from a new specimen of Gogosteus sarahae Long (1994) indicates many of the characters used to separate this genus from Incisoscutum are inconsistent and so it is here considered that the genus Gogosteus is a junior synonym of Incisoscutum. [source]

Prediction of polymorphic N -acetylation of new drug candidates by correlation with human NAT1 and NAT2

DRUG DEVELOPMENT RESEARCH, Issue 1 2002
Katalin Jemnitz
Abstract Due to interindividual variation in N -acetyltransferase 2 (NAT2) activity, pharmaceutical companies face the problem of polymorphic metabolism in drugs that are metabolized mainly or exclusively by this enzyme. An in vitro method has been developed to predict in vivo polymorphic N -acetylation at an early stage of drug development. Two new type 5H-2,3-benzodiazepine derivatives, Nerisopam (NER) with anxiolytic activity and GYKI47261 with antiepileptic activity, are metabolized mainly by N -acetylation in the rat and human. The selectivity of human N -acetyltransferases (NAT1,2) to form the acetylated metabolites has been investigated by correlation analysis. Twelve human liver samples were characterized for NAT1 and NAT2 phenotype based on their enzyme activity toward two selective NAT1 (p -aminobenzoic acid, PABA; p -aminosalicylic acid, PAS) and two selective NAT2 (sulfamethazine, SMZ; procainamide, PROC) substrates. Significant correlation was found between enzyme activities NAT1PABA/NAT1PAS and NAT2SMZ/NAT2PROC, respectively, and no correlation was observed comparing enzyme activities toward NAT1PABA/NAT2PROC. Enzyme activities using NER and GYKI 47261 as substrates were compared to activities obtained with NAT1 and NAT2 selective substrates, and the correlation coefficients were calculated. Good correlation was established between the rates of acetylation of the two drugs and that of the NAT2 selective substrate (NER/NAT2SMZ, r2=0.91, GYKI 47261/NAT2SMZ, r2=0.91). In contrast, no correlation was found between the rate of conjugation of the drugs and that of NAT1 selective substrate (NER/NAT1PABA, r2=0.022, GYKI 47261/NAT1PABA, r2=0.0004), suggesting polymorphic in vivo metabolism, since both drugs are acetylated preferably by NAT2. According to our results, correlation analysis based on in vitro acetylation activity may be used to predict in vivo polymorphic metabolism. Drug Dev. Res. 56:17,22, 2002. © 2002 Wiley-Liss, Inc. [source]

Atlantic salmon Salmo salar L., brown trout Salmo trutta L. and Arctic charr Salvelinus alpinus (L.): a review of aspects of their life histories

ECOLOGY OF FRESHWATER FISH, Issue 1 2003
A. Klemetsen
Abstract ,,,Among the species in the family Salmonidae, those represented by the genera Salmo, Salvelinus, and Oncorhynchus (subfamily Salmoninae) are the most studied. Here, various aspects of phenotypic and life-history variation of Atlantic salmon Salmo salar L., brown trout Salmo trutta L., and Arctic charr Salvelinus alpinus (L.) are reviewed. While many strategies and tactics are commonly used by these species, there are also differences in their ecology and population dynamics that result in a variety of interesting and diverse topics that are challenging for future research. Atlantic salmon display considerable phenotypic plasticity and variability in life-history characters ranging from fully freshwater resident forms, where females can mature at approximately 10 cm in length, to anadromous populations characterised by 3,5 sea-winter (5SW) salmon. Even within simple 1SW populations, 20 or more spawning life-history types can be identified. Juveniles in freshwater can use both fluvial and lacustrine habitats for rearing, and while most smolts migrate to sea during the spring, fall migrations occur in some populations. At sea, some salmon undertake extensive oceanic migrations while other populations stay within the geographical confines of areas such as the Baltic Sea. At the other extreme are those that reside in estuaries and return to freshwater to spawn after spending only a few months at sea. The review of information on the diversity of life-history forms is related to conservation aspects associated with Atlantic salmon populations and current trends in abundance and survival. Brown trout is indigenous to Europe, North Africa and western Asia, but was introduced into at least 24 countries outside Europe and now has a world-wide distribution. It exploits both fresh and salt waters for feeding and spawning (brackish), and populations are often partially migratory. One part of the population leaves and feeds elsewhere, while another part stays as residents. In large, complex systems, the species is polymorphic with different size morphs in the various parts of the habitat. Brown trout feed close to the surface and near shore, but large individuals may move far offshore. The species exhibits ontogenetic niche shifts partly related to size and partly to developmental rate. They switch when the amount of surplus energy available for growth becomes small with fast growers being younger and smaller fish than slow growers. Brown trout is an opportunistic carnivore, but individuals specialise at least temporarily on particular food items; insect larvae are important for the young in streams, while littoral epibenthos in lakes and fish are most important for large trout. The sexes differ in resource use and size. Females are more inclined than males to become migratory and feed in pelagic waters. Males exploit running water, near-shore and surface waters more than females. Therefore, females feed more on zooplankton and exhibit a more uniform phenotype than males. The Arctic charr is the northernmost freshwater fish on earth, with a circumpolar distribution in the Holarctic that matches the last glaciation. Recent mtDNA studies indicate that there are five phylogeographic lineages (Atlantic, Arctic, Bering, Siberian and Acadian) that may be of Pleistocene origin. Phenotypic expression and ecology are more variable in charr than in most fish. Weights at maturation range from 3 g to 12 kg. Population differences in morphology and coloration are large and can have some genetic basis. Charr live in streams, at sea and in all habitats of oligotrophic lakes, including very deep areas. Ontogenetic habitat shifts between lacustrine habitats are common. The charr feed on all major prey types of streams, lakes and near-shore marine habitats, but has high niche flexibility in competition. Cannibalism is expressed in several cases, and can be important for developing and maintaining bimodal size distributions. Anadromy is found in the northern part of its range and involves about 40, but sometimes more days in the sea. All charr overwinter in freshwater. Partial migration is common, but the degree of anadromy varies greatly among populations. The food at sea includes zooplankton and pelagic fish, but also epibenthos. Polymorphism and sympatric morphs are much studied. As a prominent fish of glaciated lakes, charr is an important species for studying ecological speciation by the combination of field studies and experiments, particularly in the fields of morphometric heterochrony and comparative behaviour. [source]

Variation in gene content among geographically diverse Sulfolobus isolates

ENVIRONMENTAL MICROBIOLOGY, Issue 1 2008
Dennis W. Grogan
Summary The ability of competitive (i.e., comparative) genomic hybridization (CGH) to assess similarity across entire microbial genomes suggests that it should reveal diversification within and between natural populations of free-living prokaryotes. We used CGH to measure relatedness of genomes drawn from Sulfolobus populations that had been shown in a previous study to be diversified along geographical lines. Eight isolates representing a wide range of spatial separation were compared with respect to gene-specific tags based on a closely related reference strain (Sulfolobus solfataricus P2). For the purpose of assessing genetic divergence, 232 loci identified as polymorphic were assigned one of two alleles based on the corresponding fluorescence intensities from the arrays. Clustering of these binary genotypes was stable with respect to changes in the threshold and similarity criteria, and most of the groupings were consistent with an isolation-by-distance model of diversification. These results indicate that increasing spatial separation of geothermal sites correlates not only with minor sequence polymorphisms in conserved genes of Sulfolobus (demonstrated in the previous study), but also with the regions of difference (RDs) that occur between genomes of conspecifics. In view of the abundance of RDs in prokaryotic genomes and the relevance that some RDs may have for ecological adaptation, the results further suggest that CGH on microarrays may have advantages for investigating patterns of diversification in other free-living archaea and bacteria. [source]

SPATIAL AND TEMPORAL DYNAMICS IN A SEXUAL SELECTION MOSAIC

EVOLUTION, Issue 4 2008
Thomas P. Gosden
Selective regimes and phenotypic optima could either change smoothly and in a clinal fashion or be spatially organized in a more unpredictable mosaic pattern over the geographic landscape. When natural or sexual selection is driven by intra- or interspecific biotic interactions, fine-grained spatial variation in selective regimes could result in selection mosaics rather than clinal variation in selection. We investigated temporal variation and spatial organization in sexual selection on male body size along an ecological coastal-inland gradient of a polymorphic damselfly Ischnura elegans. Body size increased in a clinal fashion along this gradient: animals were smaller in size at the coast, but became larger in the inland areas. In contrast, the sexual selection regimes on male body size showed evidence of more fine-grained spatial organization with no evidence for a clinal pattern and low spatial autocorrelations between populations. These spatially fine-grained sexual selection regimes varied in sign and magnitude and were driven by a combination of the densities of heritable female color morphs and local female body sizes. We suggest that the spatial organization of the selective regimes can be interpreted as a sexual selection mosaic that is influenced by highly localized density- and frequency-dependent social interactions. [source]

NATURAL SELECTION ON A POLYMORPHIC DISEASE-RESISTANCE LOCUS IN IPOMOEA PURPUREA

EVOLUTION, Issue 2 2007
Joel M. Kniskern
Although disease-resistance polymorphisms are common in natural plant populations, the mechanisms responsible for this variation are not well understood. Theoretical models predict that balancing selection can maintain polymorphism within a population if the fitness effects of a resistance allele vary from a net cost to a net benefit, depending upon the extent of pathogen damage. However, there have been a few attempts to determine how commonly this mechanism operates in natural plant,pathogen interactions. Ipomoea purpurea populations are often polymorphic for resistance and susceptibility alleles at a locus that influences resistance to the fungal pathogen, Coleosporium ipomoeae. We measured the fitness effects of resistance over three consecutive years at natural and manipulated levels of damage to characterize the type of selection acting on this locus. Costs of resistance varied in magnitude from undetectable to 15.5%, whereas benefits of resistance sometimes equaled, but never exceeded, these costs. In the absence of net benefits of resistance at natural or elevated levels of disease, we conclude that selection within individual populations of I. purpurea probably does not account completely for maintenance of this polymorphism. Rather, the persistence of this polymorphism is probably best explained by a combination of variable selection and meta-population processes. [source]

NATURAL VARIATION FOR A HYBRID INCOMPATIBILITY BETWEEN TWO SPECIES OF MIMULUS

EVOLUTION, Issue 1 2007
Andrea L. Sweigart
Understanding the process by which hybrid incompatibility alleles become established in natural populations remains a major challenge to evolutionary biology. Previously, we discovered a two-locus Dobzhansky,Muller incompatibility that causes severe hybrid male sterility between two inbred lines of the incompletely isolated wildflower species, Mimulus guttatus and M. nasutus. An interspecific cross between these two inbred lines revealed that the M. guttatus (IM62) allele at hybrid male sterility 1 (hms1) acts dominantly in combination with recessive M. nasutus (SF5) alleles at hybrid male sterility 2 (hms2) to cause nearly complete hybrid male sterility. In this report, we extend these genetic analyses to investigate intraspecific variation for the hms1,hms2 incompatibility in natural populations of M. nasutus and M. guttatus, performing a series of interspecific crosses between individuals collected from a variety of geographic locales. Our results suggest that hms2 incompatibility alleles are common and geographically widespread within M. nasutus, but absent or rare in M. guttatus. In contrast, the hms1 locus is polymorphic within M. guttatus and the incompatibility allele appears to be extremely geographically restricted. We found evidence for the presence of the hms1 incompatibility allele in only two M. guttatus populations that exist within a few kilometers of each other. The restricted distribution of the hms1 incompatibility allele might currently limit the potential for the hms1,hms2 incompatibility to act as a species barrier between sympatric populations of M. guttatus and M. nasutus. Extensive sampling within a single M. guttatus population revealed that the hms1 locus is polymorphic and that the incompatibility allele appears to segregate at intermediate frequency, a pattern that is consistent with either genetic drift or natural selection. [source]

MULTILOCUS GENETICS AND THE COEVOLUTION OF QUANTITATIVE TRAITS

EVOLUTION, Issue 7 2006
Michael Kopp
Abstract We develop and analyze an explicit multilocus genetic model of coevolution. We assume that interactions between two species (mutualists, competitors, or victim and exploiter) are mediated by a pair of additive quantitative traits that are also subject to direct stabilizing selection toward intermediate optima. Using a weak-selection approximation, we derive analytical results for a symmetric case with equal locus effects and no mutation, and we complement these results by numerical simulations of more general cases. We show that mutualistic and competitive interactions always result in coevolution toward a stable equilibrium with no more than one polymorphic locus per species. Victimexploiter interactions can lead to different dynamic regimes including evolution toward stable equilibria, cycles, and chaos. At equilibrium, the victim is often characterized by a very large genetic variance, whereas the exploiter is polymorphic in no more than one locus. Compared to related one-locus or quantitative genetic models, the multilocus model exhibits two major new properties. First, the equilibrium structure is considerably more complex. We derive detailed conditions for the existence and stability of various classes of equilibria and demonstrate the possibility of multiple simultaneously stable states. Second, the genetic variances change dynamically, which in turn significantly affects the dynamics of the mean trait values. In particular, the dynamics tend to be destabilized by an increase in the number of loci. [source]

DIFFERENTIAL PERFORMANCE AMONG LDH-B GENOTYPES IN RANA LESSONAE TADPOLES

EVOLUTION, Issue 5 2000
Hansjürg Hotz
Abstract The European pool frog, Rana lessonae, is widely polymorphic for two common alleles (b, e) at the lactate dehydrogenase-B (LDH-B) locus. We compared fitness-related larval life-history traits among LDH-B genotypes, which originated from segregation in heterozygous parents, in an artificial pond experiment where tadpoles of R. lessonae from a Swiss population were raised together with tadpoles of the hemiclonal hybrid R. esculenta at two densities. In R. lessonae, LDH-B e/e homozygotes at each density had a higher proportion of metamorphs among survivors, reached metamorphosis earlier, and were heavier at metamorphosis than b/b homozygotes; b/e heterozygotes had intermediate values. That e/e individuals were superior to b/b in both time to and mass at metamorphosis is surprising because these two life-history traits are thought to reflect a performance trade-off; e/e genotypes apparently compensated for shorter time to metamorphosis by a higher growth rate. The two alleles showed the same performance ranking when combined in hybrids with a R. ridibunda allele: When R. esculenta from Swiss populations reared in the same ponds had received the e allele rather than the b allele from their R. lessonae parent, they reached metamorphosis earlier, but did not differ in mass at metamorphosis. The degree of linkage disequilibrium in the source population of the eight R. lessonae used as parents of the R. lessonae tadpoles is unknown, so we cannot exclude the possibility that the performance differences are caused by some anonymous tightly linked gene, rather than the LDH-B locus, that constitutes the genomically localized target of natural selection. A causal involvement of LDH-B is plausible, nevertheless, because this enzyme takes part in the central energy-metabolizing processes and has been reported to underlie fitness differences in other animals; also, differential performance of LDH-B genotypes has been observed in R. lessonae larvae from another population. The present results suggest strong directional selection for allele e; the sum of available data, including an independent laboratory experiment, suggests that partial environment-dependent overdominance combined with balancing selection favoring e/e homozygotes under some and b/b homozygotes under other conditions may be partially responsible for the broad maintenance of the LDH-B polymorphism in R. lessonae. [source]

Microevolutionary analysis of the nematode genus Pristionchus suggests a recent evolution of redundant developmental mechanisms during vulva formation

EVOLUTION AND DEVELOPMENT, Issue 4 2001
Jagan Srinivasan
SUMMARY To identify the mechanisms by which molecular variation is introduced into developmental systems, microevolutionary approaches to evolutionary developmental biology have to be taken. Here, we describe the molecular and developmental characterization of laboratory strains of the nematode genus Pristionchus, which lays a foundation for a microevolutionary analysis of vulva development. We describe 13 laboratory strains of the Pristionchus genus that are derived from natural isolates from around the world. Mating experiments and ITS sequence analysis indicated that these 13 strains represent four different species: the gonochoristic species P. lheritieri and three hermaphroditic species, P. pacificus, P. maupasi, and an as yet undescribed species Pristionchus sp., respectively. P. pacificus is represented by five different strains isolated from California, Washington, Hawaii, Ontario, and Poland. Developmental differences during vulva formation are observed between strains from different species but also between strains of P. pacificus, like the strains from California and Poland. In particular, redundant developmental mechanisms present during vulva formation in P. pacificus var. California are absent in other strains. Amplified restriction fragment length polymorphism (AFLP) analyses of the P. pacificus strains revealed that the American strains are highly polymorphic. In contrast, the developmentally distinct strain from Poland is identical to the Californian strain, suggesting that the developmental differences rely on a small number of changes in developmental control genes rather than the accumulation of changes at multiple loci. [source]

Minisatellites in Saccharomyces cerevisiae genes encoding cell wall proteins: a new way towards wine strain characterisation

FEMS YEAST RESEARCH, Issue 4-5 2004
Paola Marinangeli
Abstract With the aim of developing new tools for the characterisation of wine yeasts, by means of databases available on-line we scanned the genome of Saccharomyces cerevisiae in search of potentially polymorphic targets. As we have previously observed for SED1, we found that other genes coding for cell wall proteins contain minisatellite-like sequences. A polymerase chain reaction (PCR) survey of SED1 and three of these others, namely AGA1, DAN4 and HSP150, in a population of wild S. cerevisiae demonstrated that these genes are highly polymorphic in length and represent a sink of unexplored genetic variability. The primer pairs designed on the gene open reading frames yield stable and repeatable amplification profiles that show a level of resolution that allows the clear discriminate between different strains. These can therefore be utilised for PCR-based typing of S. cerevisiae. [source]

Population genetic studies of hilsa shad, Tenualosa ilisha (Hamilton), in Bangladesh waters: evidence for the existence of separate gene pools

FISHERIES MANAGEMENT & ECOLOGY, Issue 5 2000
M. Rahman
Hilsa shad, Tenualosa ilisha (Hamilton), in Bangladesh is found in inland rivers, estuaries and the marine environment, throughout the year, but the peak catch period is during upstream migration. Tissue (white muscle, liver, brain) samples (total 640 specimens) were collected from three different localities, representing marine, brackish and fresh water, during the monsoon in the summer of the years 1993,1996 to identify genetic markers and study the population structure of this species. The samples were analysed by starch gel electrophoresis and isoelectric focusing, and stained for 15 enzymes and general muscle proteins. Only phosphoglucomutase, aspartate amino transferase, esterase and unidentified muscle proteins were found to be polymorphic. The allele frequencies for the samples collected in the marine environment deviated from corresponding samples from freshwater and estuarine localities, indicating that hilsa shad in Bangladesh waters comprise more than one gene pool. [source]

Genetic diversity and migration patterns of the aquatic macrophyte Potamogeton malaianus in a potamo-lacustrine system

FRESHWATER BIOLOGY, Issue 6 2009
YUANYUAN CHEN
Summary 1.,Previously, the Yangtze River connected thousands of shallow lakes which together formed a potamo-lacustrine system capable of sustaining a rich variety of submerged macrophytes. 2.,Potamogeton malaianus is one of the dominant submerged macrophytes in many lakes of this area. Genetic variation and population structure of P. malaianus populations from ten lakes in the potamo-lacustrine system were assessed using inter-simple sequence repeat markers. 3.,Twelve primer combinations produced a total of 166 unambiguous bands of which 117 (70.5%) were polymorphic. Potamogeton malaianus exhibited a moderate level of population genetic diversity (PP = 70.5%, HE = 0.163 and I = 0.255), as compared with that of plants in the same habitat and range. The main factors responsible for this moderate value were the plant's mixed breeding system (both sexual and asexual) and the hydrological connectivity among habitats. 4.,F statistics, calculated using different approaches, consistently revealed a moderate genetic differentiation among populations, contributing about 20% of total genetic diversity. An estimate of gene flow (using FST) suggested that gene flow played a more important role than genetic drift in the current population genetic structure of P. malaianus (Nm = 1.131). 5.,The genetic diversity of P. malaianus did not increase downstream. A high level of linkage,disequilibrium at the whole population level suggested that metapopulation processes may affect genetic structure. The migration pattern of P. malaianus was best explained by a two-dimensional stepping stone model, indicating that bird-mediated dispersal could greatly influence gene movements among lakes. [source]

Association between mitochondrial DNA 10398A>G polymorphism and the volume of amygdala

GENES, BRAIN AND BEHAVIOR, Issue 6 2008
H. Yamasue
Mitochondrial calcium regulation plays a number of important roles in neurons. Mitochondrial DNA (mtDNA) is highly polymorphic, and its interindividual variation is associated with various neuropsychiatric diseases and mental functions. An mtDNA polymorphism, 10398A>G, was reported to affect mitochondrial calcium regulation. Volume of hippocampus and amygdala is reportedly associated with various mental disorders and mental functions and is regarded as an endophenotype of mental disorders. The present study investigated the relationship between the mtDNA 10398A>G polymorphism and the volume of hippocampus and amygdala in 118 right-handed healthy subjects. The brain morphometry using magnetic resonance images employed both manual tracing volumetry in the native space and voxel-based morphometry (VBM) in the spatially normalized space. Amygdala volume was found to be significantly larger in healthy subjects with 10398A than in those with 10398G by manual tracing, which was confirmed by the VBM. Brain volumes in the other gray matter regions and all white matter regions showed no significant differences associated with the polymorphism. These provocative findings might provide a clue to the complex relationship between mtDNA, brain structure and mental disorders. [source]

Homozygous deletions within the 11q13 cervical cancer tumor-suppressor locus in radiation-induced, neoplastically transformed human hybrid cells

GENES, CHROMOSOMES AND CANCER, Issue 4 2004
Marc S. Mendonca
Studies on nontumorigenic and tumorigenic human cell hybrids derived from the fusion of HeLa (a cervical cancer cell line) with GM00077 (a normal skin fibroblast cell line) have demonstrated "functional" tumor-suppressor activity on chromosome 11. It has been shown that several of the neoplastically transformed radiation-induced hybrid cells called GIMs (gamma ray induced mutants), isolated from the nontumorigenic CGL1 cells, have lost one copy of the fibroblast chromosome 11. We hypothesized, therefore, that the remaining copy of the gene might be mutated in the cytogenetically intact copy of fibroblast chromosome 11. Because a cervical cancer tumor suppressor locus has been localized to chromosome band 11q13, we performed deletion-mapping analysis of eight different GIMs using a total of 32 different polymorphic and microsatellite markers on the long arm (q arm) of chromosome 11. Four irradiated, nontumorigenic hybrid cell lines, called CONs, were also analyzed. Allelic deletion was ascertained by the loss of a fibroblast allele in the hybrid cell lines. The analysis confirmed the loss of a fibroblast chromosome 11 in five of the GIMs. Further, homozygous deletion (complete loss) of chromosome band 11q13 band sequences, including that of D11S913, was observed in two of the GIMs. Detailed mapping with genomic sequences localized the homozygous deletion to a 5.7-kb interval between EST AW167735 and EST F05086. Southern blot hybridization using genomic DNA probes from the D11S913 locus confirmed the existence of homozygous deletion in the two GIM cell lines. Additionally, PCR analysis showed a reduction in signal intensity for a marker mapped 31 kb centromeric of D11S913 in four other GIMs. Finally, Northern blot hybridization with the genomic probes revealed the presence of a novel >15-kb transcript in six of the GIMs. These transcripts were not observed in the nontumorigenic hybrid cell lines. Because the chromosome 11q13 band deletions in the tumorigenic hybrid cell lines overlapped with the minimal deletion in cervical cancer, the data suggest that the same gene may be involved in the development of cervical cancer and in radiation-induced carcinogenesis. We propose that a gene localized in proximity to the homozygous deletion is the candidate tumor-suppressor gene. © 2004 Wiley-Liss, Inc. [source]

Cross-species amplification of Lolium microsatellites in Poa ssp

GRASSLAND SCIENCE, Issue 3 2006
Bryan Kindiger
Abstract Cross-species amplification of 47 Lolium ssp. microsatellite primers were evaluated across eight Poa species or subspecies. Of the 47 evaluated Lolium simple sequence repeat (SSR) primer pairs examined, 18 generated one or more amplification products. Of these, only two resulted in the identification of Poa ssp. microsatellite motifs, of which only one was complementary to the microsatellite motif identified in Lolium. Though few Poa ssp. microsatellite regions were identified, several of the amplification products were polymorphic within and across the Poa ssp. and could be utilized as markers in Poa ssp. intergeneric hybrid studies. Results of the research suggest the use of Lolium microsatellite derived primers to identify complementary SSR regions in Poa is not an effective approach for the development of microsatellite markers in Poa. [source]

Short rare MUC6 minisatellites-5 alleles influence susceptibility to gastric carcinoma by regulating gene,

HUMAN MUTATION, Issue 8 2010
Jeong-Ah Kwon
Abstract The human MUC6 gene, which is reported to be expressed in the stomach and gall bladder, is clustered on chromosome 11p15.5 with other secreted mucins. In this study, the genomic structure of MUC6 has been analyzed and five VNTR (minisatellites; MS1,MS5) were identified. These minisatellites were analyzed in genomic DNA extracted from 1,103 controls, 470 gastric cancer patients, and multigenerational families. Five novel minisatellites were found to be polymorphic and transmitted through meiosis by Mendelian inheritance in families. We evaluated allelic variation in these minisatellites to determine if such variation affected the susceptibility to gastric cancer. A significant association (odds ratio [OR]=7.08) between short rare MUC6,MS5 alleles and relative risks were observed for gastric cancer (95% confidence interval [CI], 1.43,35.19; P=0.005). To investigate the function of minisatellite alleles of MUC6,MS5, we examined the effects on gene expression from luciferase reporters when inserted with minisatellites. Interestingly, when the shortest allele (7TR) was inserted in the promoter, the expression level decreased over 20-fold (P<0.001) in normal and cancer cell lines. Furthermore, the cancer-specific rare allele (TR8) also showed decreased expression levels in cancer cells. Therefore, we suggest that the short rare MUC6,MS5 alleles may be related to cancer development by the regulation of MUC6 expression. Hum Mutat 31:1,8, 2010. © 2010 Wiley-Liss, Inc. [source]

Species-specific evolution of MHC class I genes in the higher primates

IMMUNOLOGICAL REVIEWS, Issue 1 2001
Erin J. Adams
Summary: Humans express three highly polymorphic ,classical' (HLA-A,B and C) and three conserved ,non-classical' (HLA-E, F and G) MHC class I genes. Their comparison with the MHC class I genes of apes and monkeys reveals the differential extent to which MHC class I genes have been preserved during primate evolution. African apes have orthologues of all six human genes, and although allelic lineages of the A and C loci are shared, these species share none of the human alleles. In Asian apes, several MHC class I genes show significant differences from the human genes, a trend which continues with the Old World monkeys, and even more so in the New World monkeys, where E and F are the only human gene orthologues. The C locus is confined to humans and apes. Multiple A -related and B -related loci have been identified in apes and Old World monkeys showing that duplication of these loci has been a common event during primate evolution. Certain of the daughter loci exhibit low polymorphism, suggesting they have adopted a non-classical function. The differing rates at which MHC class I genes have evolved during primate evolution likely reflects their differing functions in the immune response. [source]

The genomic context of natural killer receptor extended gene families

IMMUNOLOGICAL REVIEWS, Issue 1 2001
John Trowsdale
Summary: The two sets of inhibitory and activating natural killer (NK) receptor genes belong either to the Ig or to the C-type lectin superfamilies. Both are extensive and diverse, comprising genes of varying degrees of relatedness, indicative of a process of iterative duplication. We have constructed gene maps to help understand how and when NK receptor genes developed and the nature of their polymorphism. A cluster of over 15 C-type lectin genes, the natural killer complex is located on human chromosome 12p13.1, syntenic with a region in mouse that borders multiple Ly49 loci. The equivalent locus in man is occupied by a single pseudogene, LY49L. The immunoglobulin superfamily of loci, the leukocyte receptor complex (LRC), on chromosome 19q13.4, contains many polymorphic killer cell immunoglobulin-like receptor (KIR) genes as well as multiple related sequences. These include immunoglobulin-like transcript (ILT) (or leukocyte immunoglobulin-like receptor genes), leukocyte-associated inhibitory receptor genes (LAIR), NKp46, Fc,R and the platelet glycoprotein receptor VI locus, which encodes a collagen-binding molecule. KIRs are expressed mostly on NK cells and some T cells. The other LRC loci are more widely expressed. Further centromeric of the LRC are sets of additional loci with weak sequence similarity to the KIRs, including the extensive CD66(CEA) and Siglec families. The LRC-syntenic region in mice contains no orthologues of KIRs. Some of the KIR genes are highly polymorphic in terms of sequence as well as for presence/absence of genes on different haplotypes. Some anchor loci, such as KIR2DL4, are present on most haplotypes. A few ILT loci, such as ILT5 and ILT8, are polymorphic, but only ILT6 exhibits presence/absence variation. This knowledge of the genomic organisation of the extensive NK superfamilies underpins efforts to understand the functions of the encoded NK receptor molecules. It leads to the conclusion that the functional homology of human KIR and mouse Ly49 genes arose by convergent evolution. NK receptor immunogenetics has interesting parallels with the major histocompatibility complex (MHC) in which some of the polymorphic genes are ligands for NK molecules. There are hints of an ancient genetic relationship between NK receptor genes and MHC-paralogous regions on chromosomes 1, 9 and 19. The picture that emerges from both complexes is of eternal evolutionary restlessness, presumably in response to resistance to disease. This work was funded by the Wellcome Trust and the MRC [source]

Genomic organization and functional characterization of the alcohol dehydrogenase locus of Ceratitis capitata (Medfly)

INSECT MOLECULAR BIOLOGY, Issue 3 2006
Saverio Brogna
Abstract Approximately 30 kb of genomic DNA enclosing the Adh locus from the medfly, Ceratitis capitata have been cloned and about 15 kb has been structurally and functionally characterized. The locus consists of two genes, Adh-1 and Adh-2, separated by an intergenic region, which is polymorphic in size ranging from , 6.4 kb to 8.1 kb. Both genes consist of three exons and two introns. The introns are below 200 bp in size, except the 1st intron of Adh-1, which is unexpectedly long, variable in size and contains a deleted mariner -like element (postdoc). The two genes are transcribed in different orientations. The Adh-2 gene shows the typical pattern of transcription seen in the homologous genes of Drosophilidae presenting high levels of expression in the fat body, gut and ovaries. The Adh-1 gene is only expressed in the body muscle tissues of embryos, larvae and adult flies, raising the question of what its biological function may be. A DNA fragment containing bases ,102 to ,1666 relative to the first base of the initiating ATG of Adh-1 is sufficient to drive the expression of a reporter gene in body muscles of Drosophila melanogaster embryos, larvae and adult flies. The study provides further insights into the evolution of the Adh genes of higher diptera. [source]

Evidence that thalidomide modifies the immune response of patients suffering from actinic prurigo

INTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 12 2004
Iris Estrada-G PhD
Background, Actinic prurigo (AP) is a photodermatosis with a restricted ethnic distribution, mainly affecting Mestizo women (mixed Indian and European). The lesions are polymorphic and include macules, papules, crusts, hyperpigmentation and lichenification. Thalidomide, an effective immunomodulatory drug, was first used successfully to treat AP in 1973. In this work we describe the effect that thalidomide had on TNF-, sera levels and on IL-4- and IFN gamma (IFN,)-producing lymphocytes of actinic prurigo (AP) patients. Methods, Actinic prurigo patients were analyzed before and after thalidomide treatment. The percentage of IL-4+ or IFN,+ CD3+ lymphocytes was analyzed in eight of them by flow cytometry. TNF, in sera was measured by ELISA in 11 patients. Results, A direct correlation was observed between resolution of AP lesions and an increase in IFN,+ CD3+ peripheral blood mononuclear cells (P , 0.001) and a decrease in TNF, serum levels (no statistical difference). No IL-4+ CD3+ cells were detected. Conclusions, Our findings confirm that AP is a disease that has an immunological component and that thalidomide clinical efficacy is exerted not only through inhibition of TNF, synthesis, but also through modulation of INF,-producing CD3+ cells. These cells could be used as clinical markers for recovery. [source]

Association between genetic polymorphisms in the human interleukin-7 receptor ,-chain and inhalation allergy

INTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 3 2007
Z. Shamim
Summary Thymic stromal-derived lymphopoietin (TSLP) and interleukin-7 share a common receptor chain, IL-7R,. IL-7 is involved in T-cell homeostasis, and TSLP induces production of pro-allergic cytokines. The gene encoding the IL-7R, chain is polymorphic, and investigation of inhalation allergic patients compared with controls showed significant association with two alleles at position +1237 and +2087. [source]

Polymorphism of LMP2, TAP1, LMP7 and TAP2 in Brazilian Amerindians and Caucasoids: implications for the evolution of allelic and haplotypic diversity

INTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 1 2000
F. Rueda Faucz
In the class II region of the major histocompatibility complex (MHC), four genes implicated in processing of MHC class I-presented antigens have been described. Two of these (TAP1 and TAP2) code for endoplasmic reticulum membrane transporter proteins and the other two (LMP2 and LMP7) for proteasome subunits. These genes are polymorphic, although much less so than classical MHC class I and II genes. There is controversy concerning the possible functional implications of this variation. Population genetics is one of the means of investigating the evolutionary and functional significance of genetic polymorphisms; however, few populations have been analysed with respect to TAP and LMP diversity. We present here the polymorphism of TAP1, TAP2, LMP2 and LMP7 genes in the Kaingang and Guarani Amerindian tribes, and in the Caucasoid population of the Brazilian State of Paraná. Allele frequencies found in the Caucasoids were close to those described for similar populations. Amerindians had a somewhat more restricted polymorphism, and allele and haplotype frequencies differed greatly between the two tribes. Overall linkage disequilibrium (LD) between the four genes was low in the Caucasoids, but high in the Amerindians, for which significant LD was seen for all informative pairs of loci. Comparing results of this and previous studies we observed that, whenever significant LD occurs in non-Amerindians, it tends to be similar in the different ethnic groups. While this might be interpreted as evidence of co-evolution of genes in the TAP-LMP region, the high haplotypic diversity in all populations and low LD in non-Amerindians indicate absence of co-evolution of the different genes. Distributions of allele and genotype frequencies are consistent with the hypothesis of selective neutrality. We conclude that genetic polymorphism of the human TAP and LMP genes and haplotypes is of little, if any, functional significance. [source]

FISH detection of chimerism in pediatric hematopoietic stem cell transplantation

INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 3 2007
F. AYDIN
Summary Allogeneic hematopoietic stem cell transplantation (HSCT) is a well-established curative therapy for various malignant and non-malignant diseases. Successful outcome after allogeneic HSCT has been associated with donor chimerism (DC). However, the detection of residual host cells or mixed hemopoietic chimerism (MC) has indicated that donor chimerism is not obligatory following HSCT. More recently, fluorescence in situ hybridization (FISH) analysis has been applied to engraftment studies for the identification of polymorphic or sex chromosomes. In this study, chimerism status was evaluated in 48 sex-mismatched HSCT pediatric patients (17 women/31 men, mean age: 9.02 ± 3.95 years, range: 2,19) by FISH and the effect of DC or MC on outcome and long-term disease-free survival was documented. The stem cell source was bone marrow in all cases. All of the donors were human leucocyte antigen-identical siblings. FISH was performed on 156 specimens between days +13 and +1878. Donor chimerism was found in 47.9% (23/48) and MC was found in 52.1% (25/48) of the patients. Fifteen of 48 (31.25%) patients died, of whom 12 (80%) were MC and three patients (20%) were DC. The difference in chimerism status (MC or DC) was statistically significant between those patients who died and those still alive (,2 = 6.813; P = 0.009). [source]

Reproductive modes and genetic polymorphism in the tardigrade Richtersius coronifer (Eutardigrada, Macrobiotidae)

INVERTEBRATE BIOLOGY, Issue 1 2003
Lorena Rebecchi
Abstract. Allozymes were assessed by starch gel electrophoresis in 3 populations of a eutardigrade, Richtersius coronifer, with different reproductive modes. One population from Italy (with 2 sub-populations) was amphimictic and 2 populations (1 from Italy and 1 from Sweden) were parthenogenetic. All populations, irrespective of their reproductive mode, were diploid with the same chromosome number (2n=12) and had bivalents in the oocytes. Of the 14 loci analyzed, only 3 were polymorphic. The amphimictic population had a higher degree of genetic variability (mean heterozygosity >0.25) than the parthenogenetic populations (mean heterozygosity of the 2 populations <0.01). In all female populations, allele frequencies at all 3 loci deviated from Hardy-Weinberg equilibria due to heterozygote deficiency. These results support a hypothesis of automictic parthenogenesis in R. coronifer. [source]

Blood group antigens and immune responses,detailed knowledge is necessary to prevent immunization and to follow up immunized individuals

ISBT SCIENCE SERIES: THE INTERNATIONAL JOURNAL OF INTRACELLULAR TRANSPORT, Issue n1 2010
A. Husebekk
Background The immune system is educated to detect and react with foreign antigens and to tolerate self-antigen. Transfusion of blood cells and plasma and pregnancies challenge the immune system by the introduction of foreign antigens. The antigens may cause an immune response, but in many instances this is not the case and the individual is not immunised after exposure of blood group antigens. Aims The aim of the presentation is to dissect some immune responses to blood group antigens in order to understand the mechanism of immunisation. Methods The results of immune responses to blood group antigens can be detected by the presence of antibodies to the antigens. If the antibodies are of IgG class, the activated B cells have received help from antigen specific T cells. Both antibodies, B cells and T cells can be isolated from immunised individuals and studied in the laboratory. Also B-cell receptors and T-cell receptors as well as MHC molecules on antigen presenting cells can be studied and models of the immune synapses can be created in vitro. Results The most classic immune responses in transfusion medicine and in incompatible pregnancies are immune responses to the RhD antigen on red cells, HLA class I molecules on white cells and platelets and human platelet antigens. The nature of these antigens are different; RhD antigens are part of a large complex, present on red cells from RhD positive individuals and completely lacking on red cells from RhD negative individuals. It is likely that many peptides derived from this antigen complex may stimulate T cells and B cells. HLA antigens are highly polymorphic and the antigens are known to induce strong alloimmune responses. The HPA antigens are created by one amino acid difference in allotypes based on a single nucleotide polymorphism at the genetic level. HPA 1a induce immune responses in 10% of HPA 1b homozygote pregnant women. The result of these immune responses is destruction of blood cells with clinical consequences connected to the effect of transfusions or the outcome of pregnancies. Summary/Conclusions Even though there is emerging knowledge about the immune responses to some of the blood group antigens, more information must be gained in order to understand the complete picture. The action of the innate immune response initiating the adaptive immune response to blood group antigens is not well understood. A detailed understanding of both the innate ad the adaptive part of the immune response is necessary to identify individuals at risk for immunisation and to prevent immunisation to blood group antigens. [source]

Microsatellite polymorphism and genetic distances between the dog, red fox and arctic fox

JOURNAL OF ANIMAL BREEDING AND GENETICS, Issue 2 2003
J. Klukowska
Summary This study compared polymorphism of nine canine-derived microsatellites (MS) (CPH1, CPH3, CPH6, CPH11, 2004, 2010, 2140, 2168 and 2319) in three species of the family Canidae. The DNA samples of 151 dogs, 53 arctic foxes and 91 red foxes were examined. The canine-derived primers did not amplify two MS (CPH1 and CPH11) in genome samples of the arctic fox. The most polymorphic MS in the studied species was the one named 2319. For majority of the loci mean allele size was higher in the dog than in two fox species. The genetic distances between the species were estimated using three formulas: DS, Da and (,,)2. The estimated distances between both fox species were the smallest, while those between the dog and the arctic fox were the largest. Zusammenfassung Genetische Distanz zwischen Hund, Rotfuchs und arktischen Fuchs auf der Basis von Mikrosatelliten Diese Arbeit vergleicht genetische Polymorphismen an neun vom Hund abgeleiteten Mikrosatelliten (CPH1, CPH3, CPH6, CPH11, 2004, 2010, 2140, 2168 und 2319) in drei Arten der Familie der Canidae. Es wurden DNA-Proben von 151 Hunden, 53 arktischer Füchse und 91 Rotfüchse untersucht. Zwei der vom Hund übertragenen Primer (CPH1 und CPH11) führten zu keiner Amplifikation beim arktischen Fuchs. Die meisten Allele innerhalb der untersuchten Arten zeigte der Mikrosatellit 2319. An den meisten Genorten wurde beim Hund eine größere mittlere Allelgröße beobachtet als bei den beiden Fuchsarten. Die genetische Distanz zwischen den Arten wurde mit den drei Maßen Ds, Da und (,µ)2 geschätzt. Zwischen arktischem Fuchs und Rotfuchs wurde die geringste, zwischen Hund und arktischen Fuchs die größte genetische Distanz, geschätzt. [source]

Primers from the orders Osteoglossiform and Siluriform detect polymorphic microsatellite loci in sun-catfish, Horabagrus brachysoma (Teleostei: Bagridae)

JOURNAL OF APPLIED ICHTHYOLOGY, Issue 5 2006
A. Gopalakrishnan
Summary Horabagrus brachysoma (sun-catfish, Bagridae, Siluriformes) is a valuable ornamental and food fish. The stock structure of H. brachysoma, necessary to conserve its declining natural populations, is not known. Twenty-five primers developed for four fish species belonging to the orders Siluriform (3) and Osteoglossiform (1) were tested and eight primers amplified microsatellite loci in H. brachysoma. The results demonstrate that cross-priming between fish species belonging to different families and even to different orders can yield microsatellite loci. Five of eight primers each amplified two loci. However, the loci that had repeat motifs after sequencing were considered only for genotyping. Finally, eight loci were polymorphic with hree to seven alleles. Individual fish genotype data (n = 42; 21 each in two rivers) at each locus was analysed. Significant genetic heterogeneity was detected at six loci. The identified loci exhibited potential for use in population genetics application in H. brachysoma. [source]