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Molecular mapping of resistance to Fusarium head blight in the spring wheat cultivar Frontana.

Fusarium head blight (FHB) is a destructive disease of wheat. The objective of this study was to characterise the FHB resistance of the Brazilian spring wheat cultivar Frontana through molecular mapping. A population of 210 doubled-haploid lines from a cross of Frontana (partially resistant) and Remus (susceptible) was evaluated for FHB resistance during three seasons. Spray and single-spikelet inoculations were applied. The severity, incidence and spread of the disease were assessed by visual scoring. The population was genotyped with 566 DNA markers. The major QTL effect associated with FHB resistance mapped to chromosome 3A near the centromere, explaining 16% of the phenotypic variation for disease severity over 3 years. The most likely position is in the Xgwm720-Xdupw227 interval. The genomic region on 3A was significantly associated with FHB severity and incidence in all years evaluated, but not with FHB spread, indicating the prominent contribution of this QTL to resistance against initial infection. The map interval Xgwm129-Xbarc197 on chromosome 5A also showed consistent association with FHB severity and accounted for 9% of the phenotypic variation. In addition, smaller effects for FHB severity were identified on chromosomes 1B, 2A, 2B, 4B, 5A and 6B in single years. Individual QTLs for resistance to FHB spread accounted for less than 10% of the variation in trait expression. The present study indicates that FHB resistance of Frontana primarily inhibits fungal penetration (type I resistance), but has a minor effect on fungal spread after infection (type II resistance).

Analysis of Variance↗

[Methodology to determine risk zones for sleeping sickness in Côte d'Ivoire by the spatial approach].

Earth observation technology is a rapidly expanding field in which new outlets for sensor data are being found daily. However medical applications are still limited. The main obstacle is the lack of methods to link spatial data to an epidemiological data base within a given disease context. This obstacle was recently overcome in the Sinfra region of Cote d'Ivoire where a number of researchers have been working on human African trypanosomiasis (HAT) for over ten years. A geographical information system was developed to allow testing of various spatial relationships especially between the population density and disease prevalence using various methods of geostatistical analysis. Spot satellite data was then used to draw a map showing population density. The data base was used to validate processing by explaining the presence of errors due mainly to locality. Finally as a first experimental application for this methodology, a map showing the risk of HAT transmission over the entire Sinfra region was drawn based on satellite data.

Cote d'Ivoire↗

Integration of the genetic and physical maps of the chicken macrochromosomes.

A large amount of genetic mapping information has been obtained in the chicken from the East Lansing, Compton and Wageningen reference populations. Physical mapping information has however, been more limited. We have mapped 14 new clones, both genetically and physically, and all 14 have been assigned to macrochromosomes. The orientation of linkage groups E01C01C11W01 (Chr 1), E06C02W02 (Chr 2), E02C03W03 (Chr 3), E05C04W04 (Chr 4), E07E34C05W05 (Chr 5), E11C10W06 (Chr 6), E45C07W07 (Chr 7) and E43C12W11 (Chr 8) has been established. Here we present integrated maps of the eight macrochromosomes and the Z chromosome of the chicken and correlate genetic with physical distances for chromosomes 1-3 and the Z sex chromosome.

Animals↗

Ocular dominance in human V1 demonstrated by functional magnetic resonance imaging.

Very high resolution functional magnetic resonance imaging (fMRI) at a 4 Tesla (T) magnetic field was used to map ocular dominance regions in the human visual cortical layers using the blood oxygen level dependent (BOLD) contrast mechanism. The fMRI response from primary visual cortex (V1) exhibited a distribution of ocular dominance reminiscent of the single-cell recordings of Hubel and Wiesel. Pixels could be grouped into seven categories varying from left-only response to binocular-only response to right-only responses. Nonspecific responses were found in the MRI-visible draining veins as well as in the parenchyma. Although large vessel BOLD signals are easily detectable, regardless of field strength, they demonstrate a fMRI response to photic input that could not be used to distinguish ocular dominance. The difference in BOLD response between a region activated by one eye and that activated by the other is only 2.9% on average. This necessitates the use of a difference paradigm to visualize the regions of ocular dominance accurately. The data show that BOLD-based fMRI is sensitive to neuronal activity in cortical columns when using differential techniques, opening up the possibility of mapping specialized populations of neurons in humans that are not accessible to electrophysiological or other methods of invasive mapping.

Adult↗

Numerically exploring habitat fragmentation effects on populations using cell-based coupled map lattices.

We examine habitat size, shape, and arrangement effects on populations using a discrete reaction-diffusion model. Diffusion is modeled passively and applied to a cellular grid of territories forming a coupled map lattice. Dispersal mortality is proportional to the amount of nonhabitat and fully occupied habitat surrounding a given cell, with distance decay. After verifying that our model produces the results expected for single patches of uniform habitat, we investigate heterogeneous and fragmented model landscapes. In heterogeneous single-patch systems near critical patch size, populations approach Gaussian spatial distributions with total population constrained by the capacity of the most limiting cell. In fragmented habitat landscapes, threshold effects are more complex and parametrically sensitive. The results from our experiments suggest the following: the ability to achieve persistence in hyperdispersed patchy habitats by adding similarly fragmented patches requires meeting threshold reproduction rates; persistent metapopulations in which no local population is individually persistent appear when dispersal distances and reproduction rates are both high, but only within narrow parameter ranges that are close to extinction thresholds; successful use of stepping-stone patches to support metapopulation systems appears unlikely for passively diffusing species; elongated patches offer early colonization advantages, but blocky patches offer greater population resilience near extinction thresholds. A common theme running through our findings is that population viability estimates may depend on our ability to determine when population and habitat systems are approaching extinction threshold conditions.

Animals↗

Statistical analysis of direct identity-by-descent mapping.

Genetic mismatch scanning has been suggested as a method for using affected pairs of ostensibly unrelated but putatively distantly related affecteds in isolated populations to map disease genes. We model the regions of identity-by-descent of these affected pairs as a continuous time two state process with unknown parameters that depend on the (unknown) relationships, and we estimate the unknown parameters from the observed data. Simulated data involving pairs of first to fourth cousins show that the procedure thus obtained has properties similar, albeit slightly inferior, to the case where the relationships of the affected pairs, hence the parameters governing the processes, are known.

Chromosome Mapping↗

Mapping of trimethoprim resistance genes from epidemiologically related plasmids.

Trimethoprim resistance dihydrofolate reductase genes from plasmids known to be exchanging between human and animal populations were mapped. The dihydrofolate reductase gene has been highly conserved in all plasmids, but differences in the flanking regions provide evidence that the most recent exchange of plasmids between the two ecosystems has been from animals to humans.

Animals↗

Shaking the tree: mapping complex disease genes with linkage disequilibrium.

Much effort and expense are being spent internationally to detect genetic polymorphisms contributing to susceptibility to complex human disease. Concomitantly, the technology for detecting and genotyping single nucleotide polymorphisms (SNPs) has undergone rapid development, yielding extensive catalogues of these polymorphisms across the genome. Population-based maps of the correlations amongst SNPs (linkage disequilibrium) are now being developed to accelerate the discovery of genes for complex human diseases. These genomic advances coincide with an increasing recognition of the importance of very large sample sizes for studying genetic effects. Together, these new genetic and epidemiological data hold renewed promise for the identification of susceptibility genes for complex traits. We review the state of knowledge about the structure of the human genome as related to SNPs and linkage disequilibrium, discuss the potential applications of this knowledge to mapping complex disease genes, and consider the issues facing whole genome association scanning using SNPs.

Chromosome Mapping↗

Linkage disequilibrium mapping using single nucleotide polymorphisms--which population?

There is considerable interest in the potential of single nucleotide polymorphisms (SNPs) for mapping complex traits which are determined by genes of small individual effect (oligogenes). It is thought likely that many oligogenes are themselves common polymorphisms, perhaps biallelic, for which there is effectively neutral selection reflected in late age of onset. The extent of detectable linkage disequilibrium between SNP x SNP pairs and SNP x oligogene pairs is of considerable interest, particularly in the context of identifying 'favourable' populations. Unfortunately data are sparse and few populations have been extensively sampled. Polymorphisms with the appropriate characteristics that have been studied are blood groups in the Rhesus and MNS systems for which there are extensive data on four pairs of biallelics. These might be regarded as surrogates for SNP-SNP or SNP-oligogene pairs. By developing and applying an approach, previously used for major genes, to evaluate association (rho) in SNP haplotypes, it is evident that, with some exceptions, there is little difference between isolates and large populations. Furthermore it is apparent that there is useful linkage disequilibrium even for the MN-Ss locus pair (0.195 cM apart), in both large populations and isolates. This is somewhat more favourable to linkage disequilibrium mapping than a recent simulation suggests.

Alleles↗

[Estimation of the population density and its significance in gene geography].

A factor of the association between gene geographical data and populations of the mapped region was analyzed. This allowed for correction of the equations for the major statistical parameters of gene geographical maps (mean, variance, etc.) and gene geographical methods of estimating the spatial nonstationarity of data within a mapped region. The proposed approach is based on the use of the population density in a mapped region as a factor reflecting the anisotropy of the geographical space. The population density of the North Eurasian indigenous populations was mapped, and the application of the resulting map was illustrated with an example.

Anisotropy↗

Design and analysis of admixture mapping studies.

Admixture between populations originating on different continents can be exploited to detect disease susceptibility loci at which risk alleles are distributed differentially between these populations. We first examine the statistical power and mapping resolution of this approach in the limiting situation in which gamete admixture and locus ancestry are measured without uncertainty. We show that, for a rare disease, the most efficient design is to study affected individuals only. In a typical African American population (two-way admixture proportions 0.8/0.2, ancestry crossover rate 2 per 100 cM), a study of 800 affected individuals has 90% power to detect at P values <10(-5) a locus that generates a risk ratio of 2 between populations, with an expected mapping resolution (size of 95% confidence region for the position of the locus) of 4 cM. In practice, to infer locus ancestry from marker data requires Bayesian computationally intensive methods, as implemented in the program ADMIXMAP. Affected-only study designs require strong prior information on the frequencies of each allele given locus ancestry. We show how data from unadmixed and admixed populations can be combined to estimate these ancestry-specific allele frequencies within the admixed population under study, allowing for variation between allele frequencies in unadmixed and admixed populations. Using simulated data based on the genetic structure of the African American population, we show that 60% of information can be extracted in a test for linkage using markers with an ancestry information content of 36% at 3-cM spacing. As in classic linkage studies, the most efficient strategy is to use markers at a moderate density for an initial genome search and then to saturate regions of putative linkage with additional markers, to extract nearly all information about locus ancestry.

Black People↗

A more detailed map of the cystic fibrosis mutation DF508 frequencies in Europe.

When analyzed by origin, the frequency of the DF508 mutation (the main cystic fibrosis mutation) varies between population groups. We show here that the frequency of the DF508 mutation varies among different populations, being higher in northwest Europeans than in southeast European populations. The map we have constructed covers 25 countries; isofrequency curves were calculated using an original method.

Cystic Fibrosis↗

Perspective: the search for genes for type 2 diabetes in the post-genome era.

Twin and family studies have demonstrated a strong genetic component to type 2 diabetes mellitus (T2DM), but mapping the susceptibility genes that account for this risk has proved difficult. At least seven single gene defects are known to cause T2DM, often with early onset and insulin deficiency, but these causes account for 5% or less of all T2DM. A large number of candidate genes have been evaluated for typical T2DM, but few have been confirmed in multiple studies, and among these, the effect on individual risk is modest. A large number of genome-wide scans have been published in the last few years, and at least four regions show evidence in multiple studies. However, only NIDDM1 has been mapped to a single gene, and that gene (calpain 10) appears to have a major role only in selected populations. Work is ongoing in many laboratories and multiple populations to map additional regions, but T2DM and other complex diseases have proved recalcitrant to current methodology. In addition to the ongoing progress in completing the genome sequence and in developing a comprehensive map of single nucleotide polymorphisms, new statistical models will be needed to incorporate the multiple loci with modest effect and the known environmental interactions that characterize the susceptibility to T2DM.

Animals↗

Mapping with a few plants: using selective mapping for microsatellite saturation of the Prunus reference map.

The concept of selective (or bin) mapping is used here for the first time, using as an example the Prunus reference map constructed with an almond x peach F2 population. On the basis of this map, a set of six plants that jointly defined 65 possible different genotypes for the codominant markers mapped on it was selected. Sixty-three of these joint genotypes corresponded to a single chromosomal region (a bin) of the Prunus genome, and the two remaining corresponded to two bins each. The 67 bins defined by these six plants had a 7.8-cM average length and a maximum individual length of 24.7 cM. Using a unit of analysis composed of these six plants, their F1 hybrid parent, and one of the parents of the hybrid, we mapped 264 microsatellite (or simple-sequence repeat, SSR) markers from 401 different microsatellite primer pairs. Bin mapping proved to be a fast and economic strategy that could be used for further map saturation, the addition of valuable markers (such as those based on microsatellites or ESTs), and giving a wider scope to, and a more efficient use of, reference mapping populations.

Chromosome Mapping↗

A linkage map of sweet cherry based on RAPD analysis of a microspore-derived callus culture population.

A partial linkage map was constructed for the sweet cherry (Prunus avium L.) cultivar Emperor Francis from a population of 56 microspore-derived callus culture individuals. The callus cultures were genotyped for two allozymes and 90 random amplified polymorphic DNA (RAPD) markers using 79 random decanucleotide DNA primers and the polymerase chain reaction (PCR). Eighty-nine markers mapped to 10 linkage groups totaling 503.3 cM. DNA blot and hybridization analysis using five cloned RAPDs as probes demonstrated that one of the decanucleotide primers amplified a region of the Emperor Francis genome containing a unique sequence, whereas the other four decanucleotide primers amplified regions of the Emperor Francis genome containing repeated sequences. The five cloned RAPD probes also recognized putative homologous regions in ground cherry, P.fruticosa Pall., and sour cherry, P. cerasus L., a naturally occurring allopolyploid between P.fruticosa and P.avium.

Base Sequence↗

Canine genomics and genetics: running with the pack.

The domestication of the dog from its wolf ancestors is perhaps the most complex genetic experiment in history, and certainly the most extensive. Beginning with the wolf, man has created dog breeds that are hunters or herders, big or small, lean or squat, and independent or loyal. Most breeds were established in the 1800s by dog fanciers, using a small number of founders that featured traits of particular interest. Popular sire effects, population bottlenecks, and strict breeding programs designed to expand populations with desirable traits led to the development of what are now closed breeding populations, with limited phenotypic and genetic heterogeneity, but which are ideal for genetic dissection of complex traits. In this review, we first discuss the advances in mapping and sequencing that accelerated the field in recent years. We then highlight findings of interest related to disease gene mapping and population structure. Finally, we summarize novel results on the genetics of morphologic variation.

Animals↗

Cell cycle-dependent changes in the dynamics of MAP 2 and MAP 4 in cultured cells.

To examine the behavior of microtubule-associated proteins (MAPs) in living cells, MAP 4 and MAP 2 have been derivatized with 6-iodoacetamido-fluorescein, and the distribution of microinjected MAP has been analyzed using a low light level video system and fluorescence redistribution after photobleaching. Within 1 min following microinjection of fluoresceinated MAP 4 or MAP 2, fluorescent microtubule arrays were visible in interphase or mitotic PtK1 cells. After cold treatment of fluorescent MAP 2-containing cells (3 h, 4 degrees C), microtubule fluorescence disappeared, and the only fluorescence above background was located at the centrosomes; microtubule patterns returned upon warming. Loss of microtubule immunofluorescence after nocodozole treatment was similar in MAP-injected and control cells, suggesting that injected fluorescein-labeled MAP 2 did not stabilize microtubules. The dynamics of the MAPs were examined further by FRAP. FRAP analysis of interphase cells demonstrated that MAP 2 redistributed with half-times slightly longer (60 +/- 25 s) than those for MAP 4 (44 +/- 20 s), but both types of MAPs bound to microtubules in vivo exchanged with soluble MAPs at rates exceeding the rate of tubulin turnover. These data imply that microtubules in interphase cells are assembled with constantly exchanging populations of MAP. Metaphase cells at 37 degrees C or 26 degrees C showed similar mean redistribution half-times for both MAP 2 and MAP 4; these were 3-4 fold faster than the interphase rates (MAP 2, t1/2 = 14 +/- 6 s; MAP 4, t1/2 = 17 +/- 5 s). The extent of recovery of spindle fluorescence in MAP-injected cells was to 84-94% at either 26 or 37 degrees C. Although most metaphase tubulin, like the MAPs, turns over rapidly and completely under physiologic conditions, published work shows either reduced rates or extents of turnover at 26 degrees C, suggesting that the fast mitotic MAP exchange is not simply because of fast tubulin turnover. Exchange of MAP 4 bound to telophase midbodies occurred with dynamics comparable to those seen in metaphase spindles (t1/2 = approximately 27 s) whereas midbody tubulin exchange was slow (greater than 300 s). These data demonstrate that the rate of MAP exchange on microtubules is a function of time in the cell cycle.

Animals↗

Microtubule-associated proteins of neurons.

Microtubule-associated proteins (MAP) have been identified in cultures of rat sympathetic neurons. In all of the experiments performed here, the cultures consisted of greater than 97% neurons. 26 proteins were identified in these neuronal cultures that (a) remained associated with cytoskeletons prepared with a Triton X-100-containing microtubule-stabilizing buffer, (b) were released from such cytoskeletons by incubation in microtubule-depolymerizing buffers, (c) were not detected in cytoskeletons prepared from cultures depleted of microtubules by treatment with podophyllotoxin, and (d) co-cycled with rat brain microtubule proteins. We conclude that these 26 proteins are associated with microtubules in sympathetic neurons. Two of these proteins have molecular weights of approximately 30,000 and isoelectric points of approximately 6.2; the rest of the proteins range in molecular weight from 60,000 to 76,000 and isoelectric point from 6.3 to 6.9. This latter group of MAPs was heat labile. Several other proteins in the neuronal cultures had the solubility properties and drug-lability expected of MAP. All of these proteins had apparent molecular weights greater than 200,000; one of these putative MAP co-migrated with rat brain MAP-1. We did not detect any putative MAP in these cultures that co-migrated with rat brain MAP-2. In isoelectric focusing-SDS PAGE, the 24 MAP with molecular weights of 60,000-76,000 appeared to comprise four distinct molecular weight classes. Each molecular weight class was in turn composed of several proteins that varied in isoelectric point. In peptide mapping experiments, the isoelectric variants of each molecular weight class gave rise to very similar peptide maps. These observations suggest that each molecular weight class consists of several closely related proteins. It was also determined that all except the most basic member of the four MAP classes could be phosphorylated in vivo, raising the possibility that differential phosphorylation contributed to the variation in the isoelectric points of the members of each MAP class. We performed pulse-chase experiments to further evaluate the contribution of posttranslational modification to the generation of the complex population of MAP in the molecular weight range of 60,000 to 76,000. In cultures labeled for 20 min, only the more basic members of each MAP class were detectably labeled, while in cultures labeled for 20 min and then chased for 220 min the more acidic members of the MAP classes became labeled.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗