Fine-scale Mapping Research Articles

Nasonia

What is Nasonia? A small (2–3mm) parasitoid wasp that oviposits in the pupae of flies (but not those of Drosophila!). This hymenopteran occurs naturally in bird nests and at carcasses. Three species are known: the cosmopolitan N. vitripennis and two endemic North American species, N. giraulti and N. longicornis. Nasonia is extremely easy to culture on commercially available host pupae, it has a short generation time (15 days at 25°C) and can be maintained in diapause for over one year. What is so special about Nasonia?Nasonia has haplodiploid reproduction; haploid males develop from unfertilized eggs and diploid females from fertilized eggs. Thus, all recessive traits are expressed directly in the male: this is the case for X chromosome genes in Drosophila, but with Nasonia it is true of the entire genome. An extensive forward genetic screen for developmental mutants has already been accomplished and the identification of candidate genes is under way. Unlike the honey bee and many other hymenopterans, Nasonia has no single locus complementary sex determination, which allows fully homozygous strains to be kept without inbreeding problems. Another major advantage of Nasonia is that the three species, which exhibit considerable morphological and behavioral differences, can produce viable and fertile hybrids in the laboratory. The genetic basis for these differences can thus be easily identified through QTL analysis. Nasonia is also very favorable for cell biology, with its very clear yolk and slow early development which allow easy imaging. A useful species for studying the evolution of development then? Yes. General patterns in development and evolution can only come from comparison of multiple organisms. Nasonia has a long germband mode of development, which facilitates comparison of expression patterns with Drosophila; in contrast the beetle Tribolium, also much used for studies of the evolution of development, exhibits short germband development. Transgenic and RNAi tools are also being developed for Nasonia. With respect to sex determination, it will be exciting to figure out how ploidy differences lead to determination of the two sexes. What aspects of evolutionary genetics might Nasonia illuminate?Nasonia is extensively used to study the evolution of sex ratios and speciation. Females vary the sex of their offspring by controlling whether eggs are fertilized. A number of non-Mendelian elements, including the ‘selfish’ paternal sex-ratio chromosome and cytoplasmic sex-ratio distorters illustrate genetic conflict over sex determination. Nasonia is one of the primary organisms used to investigate the evolution and mechanisms of action of Wolbachia, an intracellular bacterium which infects many arthropods. Finally, exciting work is being done, using the three cross-fertile species, on the genetic basis of hybrid incompatibilities and interspecies differences in morphology and behaviour (wingsize and courtship, for example). This takes advantage of exchange of genes or genomic regions between species and the construction of introgression lines in which a gene for a particular trait from one species is bred into another species' genetic background. Are there genomic tools available for Nasonia? Efforts are already underway to develop genetic and genomic tools for Nasonia. Visible genetic markers are known from all five chromosomes. Dense linkage maps containing RAPD, AFLP and microsatellite markers are available with a resolution of approximately 1cM, making possible whole genome screens for mutations and fine-scale mapping of genes. The total genome size is ∼335 Mb and 1cM corresponds to ∼100 Kb of genomic DNA. An embryonic cDNA library and a BAC library funded by NSF have been constructed, and the first attempts at positional cloning are underway, focusing on a major gene for wingsize. Where can I find out more?

An integrated analysis of the effects of past land use on forest herb colonization at the landscape scale

Summary 1 A framework that summarizes the direct and indirect effects of past land use on forest herb recolonization is proposed, and used to analyse the colonization patterns of forest understorey herbaceous species in a 360-ha mixed forest, grassland and arable landscape in the Dijle river valley (central Belgium). 2 Fine-scale distribution maps were constructed for 14 species. The species were mapped in 15 946 forest plots and outside forests (along parcel margins) in 5188 plots. Forest stands varied in age between 1 and more than 224 years. Detailed land-use history data were combined with the species distribution maps to identify species-specific colonization sources and to calculate colonization distances. 3 The six most frequent species were selected for more detailed statistical analysis. 4 Logistic regression models indicated that species frequency in forest parcels was a function of secondary forest age, distance from the nearest colonization source and their interaction. Similar age and distance effects were found within hedgerows. 5 In 199 forest stands, data about soils, canopy structure and the cover of competitive species were collected. The relative importance of habitat quality and spatio-temporal isolation for the colonization of the forest herb species was quantified using structural equation modelling (SEM), within the framework proposed for the effects of past land use. 6 The results of the SEM indicate that, except for the better colonizing species, the measured habitat quality variables are of minor importance in explaining colonization patterns, compared with the combination of secondary forest age and distance from colonization sources. 7 Our results suggest the existence of a two-stage colonization process in which diaspore availability determines the initial pattern, which is affected by environmental sorting at later stages.

Genome-wide association study for regions of systemic sclerosis susceptibility in a Choctaw Indian population with high disease prevalence.

Systemic sclerosis (SSc) is a complex, multisystem connective tissue disease in which genetic factors contribute to disease susceptibility. The aim of this study was to localize chromosome regions associated with susceptibility to SSc in a relatively isolated and homogeneous population of Choctaw Indians with a high prevalence of SSc. A genome-wide microsatellite screen at 10 cM resolution (400 markers) was performed in 20 Choctaw patients with SSc and 76 ethically matched controls. Based on the results of the initial screen, fine-scale microsatellite mapping at < or =1 cM resolution was performed in 10 selected chromosome regions. Allele and marker haplotype frequencies were compared between SSc patients and controls. From the genome-wide screen, 12 markers showed evidence of highly significant associations with SSc in this population (P < 0.01), while 5 other markers showed significant associations (0.01 < P < 0.05). Among these markers, loci D5S410, D6S422, D15S978, and D20S107 are near the SPARC, MHC, FBN1, and TOPOI genes, respectively, confirming the results of our previous studies, which used different markers. D1S2800 and D14S63 have been reported to show linkage to systemic lupus erythematosus (SLE) in family-based studies, and D1S206, D6S422, and D6S264 are loci on 1p21.2, 6p22.3, and 6q23-27, respectively, which are in regions reported as showing linkage to SLE and other autoimmune diseases. Other markers showing unique associations with SSc were D7S510 (7p12-11), D7S661 (7q35), D8S514 (8q24.12), D19S221 (19p13.2), D19S220 (19q13.2), D22S423 (22q13.1), DXS1068 (Xp11.4), and DXS8055 (Xq21-23). Further analysis with fine-scale microsatellite mapping revealed at least 14 potential haplotypes associated with SSc. Our findings indicate that a number of genetic loci may contribute to the high prevalence of SSc in the Choctaw and are consistent with the paradigm that some autoimmune rheumatic diseases are likely to share genetic determinants.

Linkage Disequilibrium and Inference of Ancestral Recombination in 538 Single-Nucleotide Polymorphism Clusters across the Human Genome

The prospect of using linkage disequilibrium (LD) for fine-scale mapping in humans has attracted considerable attention, and, during the validation of a set of single-nucleotide polymorphisms (SNPs) for linkage analysis, a set of data for 4,833 SNPs in 538 clusters was produced that provides a rich picture of local attributes of LD across the genome. LD estimates may be biased depending on the means by which SNPs are first identified, and a particular problem of ascertainment bias arises when SNPs identified in small heterogeneous panels are subsequently typed in larger population samples. Understanding and correcting ascertainment bias is essential for a useful quantitative assessment of the landscape of LD across the human genome. Heterogeneity in the population recombination rate, rho=4Nr, along the genome reflects how variable the density of markers will have to be for optimal coverage. We find that ascertainment-corrected rho varies along the genome by more than two orders of magnitude, implying great differences in the recombinational history of different portions of our genome. The distribution of rho is unimodal, and we show that this is compatible with a wide range of mixtures of hotspots in a background of variable recombination rate. Although rho is significantly correlated across the three population samples, some regions of the genome exhibit population-specific spikes or troughs in rho that are too large to be explained by sampling. This result is consistent with differences in the genealogical depth of local genomic regions, a finding that has direct bearing on the design and utility of LD mapping and on the National Institutes of Health HapMap project.

Fine linkage mapping enables dissection of closely linked quantitative trait loci for seed dormancy and heading in rice.

Two quantitative trait loci (QTLs) for seed dormancy (tentatively designated Sdr1) and heading date ( Hd8) have been mapped to approximately the same region on chromosome 3 by interval mapping of backcross inbred lines derived from crosses between the rice cultivars Nipponbare (japonica) and Kasalath (indica). To clarify whether Sdr1 and Hd8 could be dissected genetically, we carried out fine-scale mapping with an advanced backcross progeny. We selected a BC(4)F(1) plant, in which a small chromosomal region including Sdr1 and Hd8, on the short arm of chromosome 3, remained heterozygous, whereas all the other chromosomal regions were homozygous for Nipponbare. Days-to-heading and seed germination rate in the BC(4)F(2) plants showed continuous variation. Ten BC(4)F(2) plants with recombination in the vicinity of Sdr1 and Hd8 were selected on the basis of the genotypes of the restriction fragment length polymorphism (RFLP) markers flanking both QTLs. Genotypes of those plants for Sdr1 and Hd8 were determined by advanced progeny testing of BC(4)F(4) families. Sdr1 was mapped between the RFLP markers R10942 and C2045, and co-segregated with C1488. Hd8 was also mapped between C12534S and R10942. Six recombination events were detected between Sdr1 and Hd8. These results clearly demonstrate that Sdr1 and Hd8 were tightly linked. Nearly isogenic lines for Sdr1 and Hd8 were selected by marker-assisted selection.

Concomitant reiterative BAC walking and fine genetic mapping enable physical map development for the broad-spectrum late blight resistance region, RB.

The wild potato species Solanum bulbocastanum is a source of genes for potent late blight resistance. We previously mapped resistance to a single region of the S. bulbocastanum chromosome 8 and named the region RB (for "Resistance from S. Bulbocastanum"). We now report physical mapping and contig construction for the RB region via a novel reiterative method of BAC walking and concomitant fine genetic mapping. BAC walking was initiated using RFLP markers previously shown to be associated with late blight resistance. Subcontig extension was accomplished using new probes developed from BAC ends. Significantly, BAC end and partial BAC sequences were also used to develop PCR-based markers to enhance map resolution in the RB region. As they were developed from BAC clones of known position relative to RB, our PCR-based markers are known a priori to be physically closer to the resistance region. These markers allowed the efficient screening of large numbers of segregating progeny at the cotyledon stage, and permitted us to assign the resistance phenotype to a region of approximately 55 kb. Our markers also directed BAC walking efforts away from regions distantly related to RB in favor of the 55-kb region. Because the S. bulbocastanum genotype used in BAC library construction is heterozygous for RB (RB/rb), codominant PCR-based markers, originally developed for fine-scale mapping, were also used to determine homolog origins for individual BAC clones. Ultimately, BAC contigs were constructed for the RB region from both resistant (RB) and susceptible (rb) homologs.

Fine scale mapping of a genetic locus for conditioned fear.

Fear conditioning is one of a number of models for investigating the genetic basis of individual variation in emotion and learning. Genetic mapping using crosses between strains of laboratory mice has identified a locus on chromosome one that appears to influence not only variation in conditioned fear, but also in other validated tests of fear-related behaviour, (including the open-field and the elevated-plus maze), suggesting that the rodent locus may act in ways consistent with how a locus influencing susceptibility to anxiety in humans is believed to operate. Here we use high-resolution mapping in genetically heterogeneous mice to show that a quantitative trait locus influencing conditioned fear can be separated from loci influencing open-field activity. Mapping in two different heterogeneous stocks, the Boulder and Northport HS, gave similar map locations for open-field activity at two positions on the current mouse physical map, one at 162 Mb on chromosome one (negative log P-value 5.4) the other at 173 Mb (negative log P-value 4.8), while mapping of contextual conditioned fear in the Boulder HS identified a locus at 170 Mb (negative log P-value 5.4). Estimates of the 95% confidence intervals show that the locations do not overlap. The region containing a gene or genes that influence variation in conditioned fear is approximately 1 megabase in size and contains only one gene of known function, a pre-B cell leukaemia factor.

A note on the optimal measure of allelic association.

Association of pairs of loci due to departure of gamete frequencies from expected frequencies is called allelic association. This measure is useful for fine-scale mapping. There are several measures of allelic association in the literature. With the availability of a SNP map, the use of linkage disequilibrium to map genes is one of the central issues in the human genome project. The size of linkage disequilibrium blocks is of considerable interest. In this note, we investigate the statistical properties of a measure which is known to have the strongest theoretical population basis and be least sensitive to the marker allele frequencies. In particular, we have shown that this measure has intuitive appeal and the estimator for this measure has several statistically optimal properties such as consistency, asymptotic unbiasedness and asymptotic efficiency.

Hierarchical Modeling of Linkage Disequilibrum: Genetic Structure and Spatial Relations

Linkage disequilibrium (LD) mapping offers much promise for the positional cloning of disease-causing genes. However, conventional estimates of LD may fluctuate substantially across contiguous genomic regions, because of population-specific phenomena such as mutation, genetic drift, population structure, and variations in allele frequencies. This fluctuation makes it difficult to interpret patterns of LD and distinguish where a causal gene is located. To address this issue, we propose hierarchical modeling of LD (HLD) for fine-scale mapping. This approach incorporates information on haplotype block structure and chromosomal spatial relations to refine the pattern of LD, increasing the ability to localize disease genes. Here, we present a framework for HLD, a simulation study assessing the performance of HLD under various scenarios, and an application of HLD to existing data. This work demonstrates that hierarchical modeling of linkage disequilibrium is a valuable and flexible approach for fine-scale mapping.

Abnormal tissue-dependent polytenization of a block of chromosome 3 pericentric heterochromatin in Drosophila melanogaster.

Heterochromatic DNA sequences in the polytene chromosomes of Drosophila melanogaster salivary glands are under-replicated in wild-type strains. In salivary glands of SuUR and in the nurse cells of otu mutants, under-replication is partly suppressed and a banded structure appears within the centric heterochromatin of chromosome 3. This novel banded structure in salivary gland chromosomes was called Plato Atlantis. In order to characterize the heterochromatic component of Plato Atlantis, we constructed a fine-scale cytogenetic map of deletions with break points within centric heterochromatin (Df(3L)1-16, Df(3L)2-66, Df(3R)10-65, Df(3R)4-75 and Df(3L)6B-29 + Df(3R)6B-29). Salivary gland chromosomes show that Df(3L)1-16 removes the complete Plato Atlantis, while Df(3L)2-66 deletes the most proximal 3L regions. These deletions therefore show a substantial cytological overlap. However, in the chromosomes of nurse cells, the same deficiencies remove distinct heterochromatic blocks, with the region of overlap being almost invisible. Satellite (AATAACATAG, AAGAG) and dodecasatellite DNAs mapped in a narrow interval in salivary glands but were found in three clearly distinguishable blocks in nurse cells. The 1.688 satellite was found at a single site in salivary glands but at two sites in nurse cells. We show that newly polytenized heterochromatic structures include blocks h47-h50d of mitotic heterochromatin in salivary glands, but the additional blocks h50p, h53 and h57 are also included in nurse cell chromosomes. Tissue specificity of the patterns of abnormal heterochromatic polytenization implies differential control of DNA replication in somatic and germline cells.

Construction of a BAC library of Rosa rugosaThunb. and assembly of a contig spanning Rdr1, a gene that confers resistance to blackspot.

A BAC library to serve as a general tool for the physical mapping and positional cloning of rose genes has been constructed from Rosa rugosa DNA. With 27,264 clones the library contains 5.2 genome equivalents. The library was used to assemble a contig of BAC clones spanning Rdr1, a locus that confers resistance to blackspot. For this purpose fine-scale mapping of the target locus was achieved by bulked segregant analysis using 816 AFLP primer combinations. The target region around Rdr1 comprises about 400 kb and is covered by a minimum of six BAC clones. Furthermore, the detection of at least five resistance gene analogs of the TIR-NBS-LRR family on the contig indicates the presence of a cluster of resistance genes around Rdr1. These results will not only allow the isolation and identification of Rdr1 in the near future, but also provide the tools for the physical mapping and positional cloning of other horticulturally interesting genes in roses.

Grey seal (Halichoerus grypus) pup mortality not explained by local breeding density on North Rona, Scotland

AbstractPre‐weaning pup mortality of grey seals Halichoerus grypus in a breeding colony (North Rona, Scotland, U.K.) was examined in relation to the density of local adult females over two breeding seasons. Accurate, fine‐scale maps of daily seal locations within a GIS database permitted the extraction of measures of female density determined at a range of spatial scales from 5 to 50 m around each pup on the date of death. Adult densities around live pups provided the null distribution of adult densities, which were tested against the distribution of densities where deaths occurred. Pre‐weaning pup mortality at this colony was not related to any of our density measures. The proportion of pups dying each day showed no seasonal trends. Analysis of topographic features from a sub‐meter digital terrain model for locations where deaths occurred suggested that there were fewer mortalities in prime pupping habitats. This could have been a direct effect of habitat or the relative quality of mothers in these habitats. The distance separating mothers and pups tended to be greater on the periphery of the colony compared to more central areas. Pups in the peripheral areas may be more exposed to predation by gulls.

Fine‐scale mapping of land‐derived nitrogen in coral reefs by δ15N in macroalgae

We measured the C/N ratio and Δ15N values of two brown macroalgae δl Padina spp. and Dictyota sp., which are distributed over all the subtropical fringing reefs of the Ryukyu Islands, Japan— to evaluate the feasibility of these algae as indicators of the terrestrial nitrogen load to the reef. The correlations between the distance from the shoreline and algal C/N ratio and surrounding NO concentrations were not clear, although their average values among the reefs seemed to indicate differences in nitrogen loadings from the land. The Δ15N values of these algae, on the other hand, linearly or curvilinearly decreased from 18‰ to 12‰ with increasing distance from the shoreline, indicating the difference in nitrogen sources available to macroalgae. The slope of the decline among eight study areas had different characters, which seemed to depend on the residence time of reef seawater and the fluxes of terrestrial nitrogen. Using Δ15N values of brown algae as an indicator, we confirmed that primary producers, such as macroalgae on the reefs, assimilated land‐derived nitrogen and successfully evaluated time‐integrated effects of terrestrial nitrogen on coral reef algae, which had been missed by conventional monitoring of the water column nutrients.

Two broad-spectrum blast resistance genes, Pi9( t) and Pi2( t), are physically linked on rice chromosome 6.

To understand the molecular basis of broad-spectrum resistance to rice blast, fine-scale mapping of the two blast resistance (R) genes, Pi9( t) and Pi2( t), was conducted. These two genes were introgressed from different resistance donors, previously reported to confer resistance to many blast isolates in the Philippines, and were mapped to an approximately 10-cM interval on chromosome 6. To further test their resistance spectrum, 43 blast isolates collected from 13 countries were used to inoculate the Pi2( t) and Pi9( t) plants. Pi9( t)-bearing lines were highly resistant to all isolates tested, and lines carrying Pi2( t) were resistant to 36 isolates, confirming the broad-spectrum resistance of these two genes to diverse blast isolates. Three RAPD markers tightly linked to Pi9( t) were identified using the bulk segregant analysis technique. Twelve positive bacterial artificial chromosome (BAC) clones were identified and a BAC contig covering about 100 kb was constructed when the Pi9( t) BAC library was screened with one of the markers. A high-resolution map of Pi9( t) was constructed using BAC ends. The Pi2( t) gene was tightly linked to all of the Pi9( t) markers in 450 F(2) plants. These data suggest that Pi9( t) and Pi2( t) are either allelic or tightly linked in an approximately 100-kb region. The mapping results for Pi9( t) and Pi2( t) provide essential information for the positional cloning of these two important blast resistance genes in rice.

Fine mapping of a quantitative trait locus for twinning rate using combined linkage and linkage disequilibrium mapping.

A novel and robust method for the fine-scale mapping of genes affecting complex traits, which combines linkage and linkage-disequilibrium information, is proposed. Linkage information refers to recombinations within the marker-genotyped generations and linkage disequilibrium to historical recombinations before genotyping started. The identity-by-descent (IBD) probabilities at the quantitative trait locus (QTL) between first generation haplotypes were obtained from the similarity of the marker alleles surrounding the QTL, whereas IBD probabilities at the QTL between later generation haplotypes were obtained by using the markers to trace the inheritance of the QTL. The variance explained by the QTL is estimated by residual maximum likelihood using the correlation structure defined by the IBD probabilities. Unlinked background genes were accounted for by fitting a polygenic variance component. The method was used to fine map a QTL for twinning rate in cattle, previously mapped on chromosome 5 by linkage analysis. The data consisted of large half-sib families, but the method could also handle more complex pedigrees. The likelihood of the putative QTL was very small along most of the chromosome, except for a sharp likelihood peak in the ninth marker bracket, which positioned the QTL within a region <1 cM in the middle part of bovine chromosome 5. The method was expected to be robust against multiple genes affecting the trait, multiple mutations at the QTL, and relatively low marker density.

Variability and spatial modeling of fine-scale precipitation data for the Sonoran Desert of south-west Arizona

We present a unique new set of high spatial resolution precipitation data from a storage gauge network, for the sparsely observed northern Sonoran desert in south-west Arizona. We examine the nature and causes of the highly complex seasonal and spatial variability in the data, using fine-scale maps developed via spatial modeling and interpolation. These high-resolution maps had explained variances approaching 1·00, and precipitation errors of about 1% in winter and about 10% in summer. Seasonal precipitation ranges from near zero to almost 15 in across the area, and shows high interannual variability. Localized convectional processes lead to summer anomalies that are more spatially complex than in winter when broad-scale synoptic and frontal processes cause precipitation. In general, summer and winter precipitation variability are tied to meridional-zonal shifts and east–west movement of the respective anticyclone or trough pattern over the region. Statistical links between major weather stations in the region and precipitation across the area are spatially inconsistent, especially in the west.

Fine-Scale Mapping of Disease Loci via Shattered Coalescent Modeling of Genealogies

We present a Bayesian, Markov-chain Monte Carlo method for fine-scale linkage-disequilibrium gene mapping using high-density marker maps. The method explicitly models the genealogy underlying a sample of case chromosomes in the vicinity of a putative disease locus, in contrast with the assumption of a star-shaped tree made by many existing multipoint methods. Within this modeling framework, we can allow for missing marker information and for uncertainty about the true underlying genealogy and the makeup of ancestral marker haplotypes. A crucial advantage of our method is the incorporation of the shattered coalescent model for genealogies, allowing for multiple founding mutations at the disease locus and for sporadic cases of disease. Output from the method includes approximate posterior distributions of the location of the disease locus and population-marker haplotype proportions. In addition, output from the algorithm is used to construct a cladogram to represent genetic heterogeneity at the disease locus, highlighting clusters of case chromosomes sharing the same mutation. We present detailed simulations to provide evidence of improvements over existing methodology. Furthermore, inferences about the location of the disease locus are shown to remain robust to modeling assumptions.

Modeling fire in semi-desert grassland/oak woodland: the spatial implications

Fire-evolved forests that historically had high fire return intervals (<100 years) in the western United States are currently overstocked with fuels due to a century or more of fire suppression and anthropogenic modification. Additionally, some western rangelands have changed composition from fire maintained grasslands to grazed shrublands. Land managers are beginning to reintroduce fire to these ecosystems as a functional component. Estimating fire behavior through the use of computer simulations is one tool to assist in planning management-ignited fire. We evaluated the sensitivity of the fire model FARSITE to the level of detail in the fuels data, both spatially and quantitatively, to better understand requirements for mapping fuels to produce accurate fire simulations. Simulated fires generated using site specific fuel models mapped at 30 m and degraded to 210 m were compared to fires simulated using standard generic Northern Forest Fire Laboratory (NFFL) fuel types. Eight classes of surface fuels were mapped by classification of satellite imagery with an overall accuracy of 0.78. A percent tree canopy cover map was created from digital orthophotos using a linear regression model with an R adj 2=0.93 of field sampled percent canopy cover data to a tree canopy shadow model. The dominant site specific fuel model (63% cover) was found to agree with the most suitable NFFL fuel model. Site specific fuel models mapped at fine resolution were found to produce statistically smaller fire areas than those produced with generic fuel models mapped at a fine scale and site specific fuels mapped at a coarse scale. In the worst case scenario (low fuel moistures and high wind speeds) the average fire size was about 20% larger with the fuel map using NFFL fuel models than with the fine scale map using site specific fuel models.

The extent of linkage disequilibrium in Arabidopsis thaliana.

Linkage disequilibrium (LD), the nonrandom occurrence of alleles in haplotypes, has long been of interest to population geneticists. Recently, the rapidly increasing availability of genomic polymorphism data has fueled interest in LD as a tool for fine-scale mapping, in particular for human disease loci. The chromosomal extent of LD is crucial in this context, because it determines how dense a map must be for associations to be detected and, conversely, limits how finely loci may be mapped. Arabidopsis thaliana is expected to harbor unusually extensive LD because of its high degree of selfing. Several polymorphism studies have found very strong LD within individual loci, but also evidence of some recombination. Here we investigate the pattern of LD on a genomic scale and show that in global samples, LD decays within approximately 1 cM, or 250 kb. We also show that LD in local populations may be much stronger than that of global populations, presumably as a result of founder events. The combination of a relatively high level of polymorphism and extensive haplotype structure bodes well for developing a genome-wide LD map in A. thaliana.

Fine-scale mapping of CYP gene clusters: An example from human CYP4 family

Publisher Summary This chapter explains the way additional related loci can be searched for near CYP4All, genes and pseudogenes can be identified, and the genomic sequence assembly currently available in the public database can be evaluated. This general method can be adapted to the fine-scale mapping of any P450 gene cluster in any organism for that there is a substantial collection of genomic sequence available through GenBank. It relies throughout on data and software that are freely available to all researchers. Researchers can also continue to monitor a chromosomal region and incorporate improved sequences into their provisional maps. A small region that does not contain any repetitive element sequence can be selected from the end of a clone flanking a gap and used to search the database periodically for new, potentially overlapping sequences. Searches using cDNA sequences from unlocalized genes can also be done periodically. In this case, the true CYP4All locus is still missing.