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Heterozygous Individuals (heterozygous + individual)
Selected AbstractsPopulation Size, Genetic Variation, and Reproductive Success in a Rapidly Declining, Self-Incompatible Perennial (Arnica montana) in The NetherlandsCONSERVATION BIOLOGY, Issue 6 2000Sheila H. Luijten In 26 populations in The Netherlands we investigated the relationship between population size and genetic variation using allozyme markers. Genetic variation was low in A. montana ( He = 0.088). There were positive correlations between population size and the proportion of polymorphic loci, the number of effective alleles, and expected heterozygosity, but not with observed heterozygosity. There was a significantly positive correlation between population size and the inbreeding coefficient. Generally, small populations showed heterozygote excess, which decreased with increasing population size. Possibly, the heterozygous individuals in small populations are survivors from the formerly larger populations with relatively high fitness. The F statistics showed a moderately high level of differentiation among populations ( FST = 0.140 ± 0.02), implying a low level of gene flow. For three out of four allozyme loci, we found significant inbreeding ( FIS = 0.104 ± 0.03). Only 14 of 26 populations were in Hardy-Weinberg equilibrium at all four polymorphic loci. In a subset of 14 populations of various size, we investigated natural seed production and offspring fitness. Population size was positively correlated with seed set, seedling size, number of flowering stems and flowerheads, adult survival, and total relative fitness, but not with the number of florets per flowerhead, germination rate, or the proportion of germination. Offspring performance in the greenhouse was not associated with genetic diversity measured on their mothers in the field. We conclude that the fitness of small populations is significantly reduced, but that there is as yet no evidence that this was caused by inbreeding. Possibly, the self-incompatibility system of A. montana has been effective in reducing selfing rates and inbreeding depression. Resumen:Arnica montana es una especie de planta rara, en declinación rápida y autoincompatible. En 26 poblaciones de los Países Bajos investigamos la relación entre el tamaño poblacional y la variación genética mediante el uso de alozimas marcadoras. La variación genética fue baja en A. montana ( He = 0.088). Existió una correlación positiva entre el tamaño poblacional y la proporción de emplazamientos polimórficos, el número de alelos efectivos y la heterocigocidad esperada, pero no con la heterocigocidad observada. Existió una correlación positiva significativa entre el tamaño poblacional y el coeficiente de endogamia. Generalmente, las poblaciones pequeñas mostraron una heterocigocidad excesiva con disminuciones en el tamaño poblacional. Posiblemente, los individuos heterocigóticos de poblaciones pequeñas son sobrevivientes de poblaciones anteriormente grandes con una adaptabilidad relativamente alta. Las pruebas de F mostraron un nivel de diferenciación moderadamente alto entre poblaciones ( FST = 0.140 ± 0.02) lo que implica un nivel bajo de flujo de genes. Para tres de cuatro de los emplazamientos de alozimas encontramos una endogamia significativa ( FIS = 0.104 ± 0.03). Solamente 14 de las 26 poblaciones estuvieron en equilibrio Hardy-Weinberg para los cuatro emplazamientos polimórficos. En un subconjunto de 14 poblaciones de varios tamaños, investigamos la producción natural de semillas y la adaptabilidad de la descendencia. El tamaño poblacional estuvo positivamente correlacionado con el juego de semillas, el tamaño del almácigo, el número de tallos en flor y de inflorescencias, la supervivencia de adultos y la adaptabilidad total relativa, pero no con el número de flores por inflorescencia, la tasa de germinación ni la proporción de la germinación. El rendimiento de la descendencia en invernaderos no estuvo asociado con la diversidad genética medida en sus madres en el campo. Concluimos que la adaptabilidad de poblaciones pequeñas está significativamente reducida, pero no existe aún evidencia de que esto sea ocasionado por endogamia. Es posible que el sistema de autoincompatibilidad de A. montana haya sido efectivo en la reducción de tasas de autofecundación y depresión de la endogamia. [source] A variable number of tandem repeats polymorphism influences the transcriptional activity of the neonatal Fc receptor ,-chain promoterIMMUNOLOGY, Issue 1 2006Ulrich J. H. Sachs Summary The neonatal Fc receptor, FcRn, plays a central role in immunoglobulin G (IgG) transport across placental barriers. Genetic variations of FcRn-dependent transport across the placenta may influence antibody-mediated pathologies of the fetus and the newborn. Sequencing analysis of 20 unrelated individuals demonstrated no missense mutation within the five exons of the FcRn gene. However, a variable number of tandem repeats (VNTR) region within the FcRn promoter was observed, consisting of five different alleles (VNTR1,VNTR5). Alleles with two (VNTR2) and three (VNTR3) repeats were found to be most common in Caucasians (7·5 and 92·0%, respectively). Real-time polymerase chain reaction revealed that monocytes from VNTR3 homozygous individuals express 1·66-fold more FcRn transcript than do monocytes from VNTR2/VNTR3 heterozygous individuals (P = 0·002). In reporter plasmid assays, the VNTR3 allele supported the transcription of a reporter gene twice as effectively as did the VNTR2 allele (P = 0·003). Finally, under acidic conditions, monocytes from VNTR3 homozygous individuals showed an increased binding to polyvalent human IgG when compared with monocytes from VNTR2/VNTR3 heterozygous individuals (P = 0·021). These data indicate that a VNTR promoter polymorphism influences the expression of the FcRn receptor, leading to different IgG-binding capacities. [source] Iron-overload and genotypic expression of HFE mutations H63D/C282Y and transferrin receptor Hin6I and BanI polymorphism in German patients with hereditary haemochromatosisINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 3 2000R. Gottschalk Gene variations of HFE, a HLA-class I like molecule, are highly associated with hereditary haemochromatosis (HH). Functional as well as molecular studies of the HFE protein have indicated that the molecule is involved in iron metabolism and that the HFE gene variations observed among HH patients affect its interaction with the transferrin receptor (TfR). In the present study, we have therefore analysed the relationship between the HFE gene variants, C282Y and H63D, and body iron status among 85 German HH patients. In addition, two TfR gene polymorphism, TfR-Hin6I and TfR-BanI, were typed that have been reported to define ethnically distinct haplotypes. As controls we used 251/159 healthy German blood donors. Seventy-eight (92%) patients were C292Y homozygous, the H63D mutation was present in five (6%) patients with none of the patients being H63D homozygous. Serum transferrin, transferrin saturation and liver iron content were determined prior to therapeutic intervention. Among C282Y homozygous patients serum ferritin levels (2294 ± 3174 vs. 463 ± 224 µg L,1, P < 0.0001) and transferrin saturation (86 ± 18% vs. 62 ± 25%, P = 0.048) were elevated significantly compared with C282Y and/or H63D heterozygous patients. In addition, the liver iron content (291 ± 165 vs. 138 ± 95 µmol g,1, P = 0.028) and liver iron index (6.4 ± 2.8 vs. 3.2 ± 2.3, P = 0.019) were increased among C282Y homozygotes compared with C282Y heterozygotes. In contrast, no difference was observed between patients and controls regarding the distribution of TfR- Hin6I and TfR- BanI alleles. These data indicate that the iron intake is higher among C282Y homozygous patients compared with C282Y heterozygous or C282Y/H63D compound heterozygous individuals and supports the functional role of the HFE protein in iron metabolism whereas the TfR gene variants seem to have no influence on iron uptake. [source] Risk of ectoparasitism and genetic diversity in a wild lesser kestrel populationMOLECULAR ECOLOGY, Issue 17 2007JOAQUÍN ORTEGO Abstract Parasites and infectious diseases are major determinants of population dynamics and adaptive processes, imposing fitness costs to their hosts and promoting genetic variation in natural populations. In the present study, we evaluate the role of individual genetic diversity on risk of parasitism by feather lice Degeeriella rufa in a wild lesser kestrel population (Falco naumanni). Genetic diversity at 11 microsatellite loci was associated with risk of parasitism by feather lice, with more heterozygous individuals being less likely to be parasitized, and this effect was statistically independent of other nongenetic parameters (colony size, sex, location, and year) which were also associated with lice prevalence. This relationship was nonlinear, with low and consistent prevalences among individuals showing high levels of genetic diversity that increased markedly at low levels of individual heterozygosity. This result appeared to reflect a genome-wide effect, with no single locus contributing disproportionably to the observed effect. Thus, overall genetic variation, rather than linkage of markers to genes experiencing single-locus heterosis, seems to be the underlying mechanism determining the association between risk of parasitism and individual genetic diversity in the study host,parasite system. However, feather lice burden was not affected by individual heterozygosity; what suggest that differences in susceptibility, rather than variation in defences once the parasite has been established, may shape the observed pattern. Overall, our results highlight the role of individual genetic diversity on risk of parasitism in wild populations, what has both important evolutionary implications and major consequences for conservation research on the light of emerging infectious diseases that may endanger genetically depauperated populations. [source] Enhanced transthyretin tetramer stability following expression of an amyloid disease transsuppressor variant in mammalian cellsTHE JOURNAL OF GENE MEDICINE, Issue 2 2009Masakazu Kamata Abstract Background The transthyretin (TTR) amyloidosis is an incurable fatal inherited disease that is characterized by progressive peripheral and autonomic neuropathy. It is caused by missense amyloidogenic mutations in the TTR gene that destabilize the native tetrameric state and lead to the cytotoxic misfolded monomeric state. One interesting variant (T119M) stabilizes heterotetramers with amyloidogenic TTR and, in the reported heterozygous individuals, protects the carriers from disease. In the present study, we characterize in vitro and in vivo the ectopic expression of the human T119M mutant, termed a transsuppressor for TTR amyloid disease. Methods Lentiviral vectors encoding wild or mutant forms of human TTR were constructed and transduced to the human hepatocellular carcinoma cell line, HepG2, or mice. Heterooligomerization between T119M TTR and amyloidogenic variants was analysed by immunoprecipitation following western blotting. Results T119M TTR was stably expressed in transduced HepG2 cells and was secreted as an oligomer that can interact with its native partner, retinol-binding protein. Importantly, the T119M TTR formed secreted heterooligomers with amyloidogenic TTR variants, V30M, L55P and V122I, in HepG2 cells that were more stable than the homooligomers of the same amyloidogenic TTR variants. Human T119M TTR also formed heterooligomers with V30M TTR in transduced mice. Conclusions The results obtained in the present study demonstrate the stabilization of heterotetramers by T119M TTR in human cells and suggest that gene transfer of T119M TTR may have potential as a gene therapy for TTR amyloidosis. Copyright © 2008 John Wiley & Sons, Ltd. [source] Genetic variation in the bovine myostatin gene in UK beef cattle: Allele frequencies and haplotype analysis in the South DevonANIMAL GENETICS, Issue 5 2000J A Smith Work on Belgian Blue cattle revealed that an 11 base pair (bp) deletion within the bovine myostatin gene (GDF8) is associated with the double-muscled phenotype seen in this breed. Investigations focusing on other European breeds known to show double-muscling identified several mutations within the coding region of the gene associated with the double-muscled phenotype in different breeds. The number of mutations found suggest that myostatin is highly variable within beef cattle. Variations that alter the structure of the gene product such that the protein is inactivated are associated with the most pronounced form of double-muscling as seen in the Belgian Blue. However, other mutations may have a less extreme affect on muscle development. While overt double-muscling gives rise to a high incidence of dystocia (calving difficulty), it is possible that some variants may give enhanced muscling, but with limited calving problems. We describe sequence analysis of the myostatin gene in ten beef breeds commonly used in the UK and show that the 11-bp deletion responsible for double-muscling in the Belgian Blue is also present in the South Devon cattle population. Allele frequencies and haplotypes in the South Devon and a polymerase chain reaction (PCR) based test for the deletion are described. PCR amplification across the deleted region provides a quick and effective test with clear identification of heterozygous individuals. We discuss our results with regard to the effect of genotype on phenotype and differences observed between the Belgian Blue and the South Devon. [source] Incorporating Genotype Uncertainty into Mark,Recapture-Type Models For Estimating Abundance Using DNA SamplesBIOMETRICS, Issue 3 2009Janine A. Wright Summary Sampling DNA noninvasively has advantages for identifying animals for uses such as mark,recapture modeling that require unique identification of animals in samples. Although it is possible to generate large amounts of data from noninvasive sources of DNA, a challenge is overcoming genotyping errors that can lead to incorrect identification of individuals. A major source of error is allelic dropout, which is failure of DNA amplification at one or more loci. This has the effect of heterozygous individuals being scored as homozygotes at those loci as only one allele is detected. If errors go undetected and the genotypes are naively used in mark,recapture models, significant overestimates of population size can occur. To avoid this it is common to reject low-quality samples but this may lead to the elimination of large amounts of data. It is preferable to retain these low-quality samples as they still contain usable information in the form of partial genotypes. Rather than trying to minimize error or discarding error-prone samples we model dropout in our analysis. We describe a method based on data augmentation that allows us to model data from samples that include uncertain genotypes. Application is illustrated using data from the European badger (Meles meles). [source] Validation of MCADD newborn screeningCLINICAL GENETICS, Issue 2 2009EM Maier Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) represents a potentially fatal fatty acid ,-oxidation disorder. Newborn screening (NBS) by tandem mass spectrometry (MS/MS) has been implemented worldwide, but is associated with unresolved questions regarding population heterogeneity, burden on healthy carriers, cut-off policies, false-positive and negative rates. In a retrospective case-control study, 333 NBS samples showing borderline acylcarnitine patterns but not reaching recall criteria were genotyped for the two most common mutations (c.985A>G/c.199C>T) and compared with genotypes and acylcarnitines of 333 controls, 68 false-positives, and 34 patients. c.985A>G was more frequently identified in the study group and false-positives compared to controls (1:4.3/1:2.3 vs. 1:42), whereas c.199C>T was found more frequently only within the false-positives (1:23). Biochemical criteria were devised to differentiate homozygous (c.985A>G), compound heterozygous (c.985A>G/c.199C>T), and heterozygous individuals. Four false-negatives were identified because our initial algorithm required an elevation of octanoylcarnitine (C8) and three secondary markers in the initial and follow-up sample. The new approach allowed a reduction of false-positives (by defining high cut-offs: 1.4 ,mol/l for C8; 7 for C8/C12) and false-negatives (by sequencing the ACADM gene of few suspicious samples). Our validation strategy is able to differentiate healthy carriers from patients doubling the positive predictive value (42,88%) and to target NBS to MCADD-subsets with potentially higher risk of adverse outcome. It remains controversial, if NBS programs should aim at identifying all subsets of all diseases included. Because the natural course of milder variants cannot be assessed by observational studies, our strategy could serve as a general model for evaluation of MS/MS-based NBS. [source] | |||||||||||||