Fine-scale Mapping Research Articles

Breeding system variation, genetics and evolution in the Turneraceae

We review the genetics and evolution of breeding systems in the Turneraceae. Distyly occurs in seven of 10 genera and 81% of species. The remaining species are homostylous. Polyploid evolution has been significant in Turnera. Approximately 60% of species are polyploid ranging from diploid through decaploid. No relationship between breeding system and polyploidy is evident. The genetics of distyly involves a one-locus two-allele system (S and s). Evidence from crosses with homostylous species and mutants is consistent with the possibility that a "Primula-type" supergene underlies distyly but does not prove this to be the case. A polygalacturonase, and an alpha-dioxygenase specific to the transmitting tissue of short-styled plants both exhibit morph-limited expression in concert with predictions from an evolutionary model. The function of the proteins in distyly, if any, is unknown. We have begun constructing a fine-scale genetic map of Turnera. Two genetic markers lie within 0.2 cm of the distyly locus. This should provide a starting point for positional cloning of the distyly locus and reveal the genetic architecture and molecular basis of distyly.

AtALMT1, which encodes a malate transporter, is identified as one of several genes critical for aluminum tolerance in Arabidopsis.

Aluminum (Al) tolerance in Arabidopsis is a genetically complex trait, yet it is mediated by a single physiological mechanism based on Al-activated root malate efflux. We investigated a possible molecular determinant for Al tolerance involving a homolog of the wheat Al-activated malate transporter, ALMT1. This gene, named AtALMT1 (At1g08430), was the best candidate from the 14-member AtALMT family to be involved with Al tolerance based on expression patterns and genomic location. Physiological analysis of a transferred DNA knockout mutant for AtALMT1 as well as electrophysiological examination of the protein expressed in Xenopus oocytes showed that AtALMT1 is critical for Arabidopsis Al tolerance and encodes the Al-activated root malate efflux transporter associated with tolerance. However, gene expression and sequence analysis of AtALMT1 alleles from tolerant Columbia (Col), sensitive Landsberg erecta (Ler), and other ecotypes that varied in Al tolerance suggested that variation observed at AtALMT1 is not correlated with the differences observed in Al tolerance among these ecotypes. Genetic complementation experiments indicated that the Ler allele of AtALMT1 is equally effective as the Col allele in conferring Al tolerance and Al-activated malate release. Finally, fine-scale mapping of a quantitative trait locus (QTL) for Al tolerance on chromosome 1 indicated that AtALMT1 is located proximal to this QTL. These results indicate that AtALMT1 is an essential factor for Al tolerance in Arabidopsis but does not represent the major Al tolerance QTL also found on chromosome 1.

The Orbit and Occultations of KH 15D

The unusual flux variations of the pre-main-sequence binary star KH 15D have been attributed to occultations by a circumbinary disk. We test whether or not this theory is compatible with newly available data, including recent radial velocity measurements, CCD photometry over the past decade, and photographic photometry over the past 50 years. We find the model to be successful, after two refinements: a more realistic motion of the occulting feature, and a halo around each star that probably represents scattering by the disk. The occulting feature is exceptionally sharp-edged, raising the possibility that the dust in the disk has settled into a thin layer, and providing a tool for fine-scale mapping of the immediate environment of a T Tauri star. However, the window of opportunity is closing, as the currently visible star may be hidden at all orbital phases by as early as 2008.

High resolution topsoil mapping using hyperspectral image and field data in multivariate regression modeling procedures

The spatial variability of within field topsoil texture and organic matter was studied using airborne hyperspectral imagery so as to develop improved fine-scale soil mapping procedures. Two important topsoil variables for precision farming applications, soil organic matter and soil texture, were found to be correlated with spectral properties of the airborne HyMap scanner. The percentage sand, clay, organic carbon and total nitrogen content could be predicted quantitatively and simultaneously by a multivariate calibration approach using either partial least-square regression (PLSR) or multiple linear regression (MLR). The different topsoil parameters are determined simultaneously from the spectral signature contained in the single hyperspectral image, since the various variables were represented by varying combinations of wavebands across the spectra. The methodology proposed provides a means of simultaneously estimating topsoil organic matter and texture in a rapid and non-destructive manner, whilst avoiding the spatial accuracy problems associated with spatial interpolation. The use of high spatial resolution and hyperspectral remotely sensed data in the manner proposed in this paper can also be used to monitor and better understand the influence of management and land use practices on soil organic matter composition and content.

The utility of site‐based datasets and regional ecosystem mapping for biodiversity conservation in the Southeast Queensland Bioregion: Past, present, future

The utility of site-based datasets and regional ecosystem mapping for biodiversity conservation in the Southeast Queensland Bioregion: Past, present, future. Ben E. Lawson. School of Natural and Rural Systems Management (NRSM) & School of Geography, Planning and Architecture (GPA), The University of Queensland, Brisbane 4072, Australia. Email: b.lawson@uq.edu.au. Key words: conservation, ecosystem mapping, regional ecosystems, site-based data. Ecosystem mapping and site-based datasets are core components of conservation planning and management schemes. In Queensland, regional ecosystem mapping is used for landscape-level planning, underpinned by site-based data. This doctoral research assesses their utility as surrogates for biodiversity patterns with a view to future needs. The research is supervised by Dr Grant Wardell-Johnson, Associate Professor Bob Beeton (NRSM) and Dr David Pullar (GPA) from the University of Queensland. The ecologically diverse Southeast Queensland (SEQ) Bioregion is the focus of this research. Issues and limitations in the two datasets, which underpin this research, were the first component examined. Regional ecosystem mapping showed a decrease in the number of heterogeneous polygons (i.e. a polygon with multiple ecosystems assigned) across successive versions. Polygon heterogeneity levels were positively correlated with endangered ecosystems and lower polygon accuracy, and strongly related to particular regional ecosystem and geomorphology types (see Lawson 2006). Retrospective analysis of the Queensland Herbarium's site-based floristic dataset, ‘CORVEG’, showed improved data quality and completeness in the past decade as a consequence of more explicit sampling protocols, although missing information continues to limit data utility (see Lawson in press). Case studies were used to explore the application of regional ecosystem mapping in varied circumstances. The first case study examined SEQ sand islands where high levels of map unit homogeneity relative to adjacent mainland areas were observed. Analysis showed that mapping effectively portrayed ecological patterns and that homogeneity existed across various map scales and map authors across the islands, suggesting that high polygon homogeneity were ecological, not cartographic, phenomena (see Lawson & Wardell-Johnson in press). The second case study came from Toohey Forest in southern SEQ, an area mapped as a single regional ecosystem type at 1:100 000 scale despite its recognized biotic and abiotic diversity. Fine-scale mapping approaches were explored to assess the representation of floristic patterns, indicating that ongoing reduction in regional ecosystem mapping scale and incorporation of fine-scale geomorphic mapping were vital to improve the representation of floristic diversity. Core components of the research which are yet to be completed will elucidate species richness and dissimilarity patterns within and between map units and reveal the ecosystem types that are (and aren't) well portrayed by the mapped patterns, the reasons for this, and measures to improve representation. Queensland's regional ecosystem mapping program shows continued improvement in the representation of biodiversity patterns, with some areas more effectively portrayed than others. The use of heterogeneous polygons to identify ecosystems otherwise unrecognizable at particular map scales is simultaneously a major advantage and disadvantage to representing biodiversity patterns. Opportunities are available to focus limited resources on particular geomorphological and regional ecosystem types, and for alternate methods of representing geographically restricted ecosystems. Greater consideration of current and future uses of site-based floristic data is necessary. For example, hierarchical datasets serving multiple biodiversity objectives should be considered. These issues are directly relevant to the mapping of biodiversity condition.

Rapid inventory of wild medicinal plant populations in Sri Lanka

Sustainable use of wild populations of medicinal plants (as with other non-timber forest products) requires robust assessment of the distribution and abundance of target species. Long-term population dynamics datasets are typically unavailable in many developing countries, and then perhaps only for one to few high profile taxa. Given the scale and urgency of sustainability issues, one-off inventories provide the only realistic means for assessing the population status and harvest potential of assemblages of target resource species. Quantitative examples of such assessments are very rare, and limited in scale. As part of a national programme focusing on developing sustainable usage of medicinal plants in five biogeographically representative Medicinal Plant Conservation Areas (MPCAs) in Sri Lanka, we describe the rapid appraisal methodology developed for, and substantive results derived from, a resource inventory undertaken at respective MPCAs to provide: (a) baseline assessment of the distributions, associated population structures and densities, and ecological requirements of medicinal plant species; and (b) an informed basis for ongoing in situ conservation, management, and harvest sustainability of defined priority medicinal plant species. The applied methodology comprised: (a) quantitative assessment of medicinal plant populations and habitat features at 898 inventory plots, located using a strict hierarchical stratification; (b) standard numerical classificatory procedures to define major habitat types; and (c) areal estimates of habitats based on available fine-scale topographic mapping, augmented with refined mapping derived from Landsat TM imagery. Over 1400 medicinal plant species (ca. 40% of the national flora) were sampled during the inventory, occurring in habitat conditions ranging from dense-canopied, relatively undisturbed tropical forest, to savanna. Most vegetation was of a secondary nature reflecting ancient and varied histories of chena (slash and burn) cultivation, grassland/savanna burning for pastoral purposes, and recent logging. Medicinal plant species density was significantly correlated overall with higher rainfall, higher elevation, deeper and more acid soils. Derived population estimates and structures, and the potential for sustainable harvest from the wild, are assessed for 34 priority medicinal plant species. Results demonstrate the very low resource base of most priority species, and the varied habitat and disturbance requirements of medicinal plants in Sri Lankan reserves. It follows that (a) greater attention needs to be given to ex situ propagation and farming of medicinal plant resources—although for many long-lived perennial taxa this is likely to be impractical; (b) there can be no one management prescription which caters for all component species; and (c) for effective conservation local communities need to be actively involved in managing natural vegetation habitats (albeit under regulated conditions), including imposition of various forms of small-scale disturbances such as harvesting and, where appropriate, fire management.

GeneRecon—a coalescent based tool for fine-scale association mapping

GeneRecon is a tool for fine-scale association mapping using a coalescence model. GeneRecon takes as input case-control data from phased or unphased SNP and microsatellite genotypes. The posterior distribution of disease locus position is obtained by Metropolis-Hastings sampling in the state space of genealogies. Input format, search strategy and the sampled statistics can be configured through the Guile Scheme programming language embedded in GeneRecon, making GeneRecon highly configurable. The source code for GeneRecon, written in C++ and Scheme, is available under the GNU General Public License (GPL) at http://www.birc.au.dk/~mailund/GeneRecon mailund@birc.au.dk.

Gene evolution at the ends of wheat chromosomes

Wheat ESTs mapped to deletion bins in the distal 42% of the long arm of chromosome 4B (4BL) were ordered in silico based on blastn homology against rice pseudochromosome 3. The ESTs spanned 29 cM on the short arm of rice chromosome 3, which is known to be syntenic to long arms of group-4 chromosomes of wheat. Fine-scale deletion-bin and genetic mapping revealed that 83% of ESTs were syntenic between wheat and rice, a far higher level of synteny than previously reported, and 6% were nonsyntenic (not located on rice chromosome 3). One inversion spanning a 5-cM region in rice and three deletion bins in wheat was identified. The remaining 11% of wheat ESTs showed no sequence homology in rice and mapped to the terminal 5% of the wheat chromosome 4BL. In this region, 27% of ESTs were duplicated, and it accounted for 70% of the recombination in the 4BL arm. Globally in wheat, no sequence homology ESTs mapped to the terminal bins, and ESTs rarely mapped to interstitial chromosomal regions known to be recombination hot spots. The wheat-rice comparative genomics analysis indicated that gene evolution occurs preferentially at the ends of chromosomes, driven by duplication and divergence associated with high rates of recombination.

Measuring long-term ecological changes in densely populated landscapes using current and historical high resolution imagery

Long-term ecological changes within densely populated landscapes account for a growing share of global environmental change. Measuring the causes and consequences of these changes remains a challenge because of their fine spatial scale and complexity. Here, we measure long-term ecological changes, circa 1950 to 2002, within six 1 km 2 sites in densely populated rural China and in urban and suburban Baltimore, Maryland, USA using a standardized procedure for fine-scale feature-based ecological mapping from high spatial resolution (≤ 1 m) imagery. The median size of ecologically distinct landscape features (ecotopes) mapped by this procedure was just 520 m 2, though size, count and perimeter of features varied considerably both within and between sites. Land management and vegetation cover changed substantially, over 28% to 87% of site areas, but most of this change occurred in small patches with area < 4000 m 2. Landscape complexity also increased over time by the fragmentation of landscapes into a larger number of smaller features with an increasing diversity of ecotope classes. Detailed analysis of fine-scale landscape transformations helped identify the causes and consequences of ecologically significant changes within and across sites, including unexpected increases in perennial vegetation cover and the linkage of impervious surface area with population density. These and other results demonstrate the general utility of anthropogenic ecotope mapping as a tool for cross-site comparison and sampled regional estimates of long-term ecological changes within densely populated landscapes.

Fine-mapping using the weighted average method for a case-control study

We present a new method for fine-mapping a disease susceptibility locus using a case-control design. The new method, termed the weighted average (WA) statistic, averages the Cochran-Armitage (CA) trend test statistic and the difference between the Hardy-Weinberg disequilibrium test statistic for cases and controls (the HWD trend). The main characteristics of the WA statistic are that it improves on the weaknesses, and maintains the strengths, of both the CA trend test and the HWD trend test. Data from three different populations in the Genetic Analysis Workshop 14 (GAW14) simulated dataset (Aipotu, Karangar, and Danacaa) were first subjected to model-free linkage analysis to find regions exhibiting linkage. Then, for fine-scale mapping, 140 SNPs within the significant linkage regions were analyzed with the WA test statistic on replicates of the three populations, both separately and combined. The regions that were significant in the multipoint linkage analysis were also significant in this fine-scale mapping. The most significant regions that were obtained using the WA statistic were regions in chromosome 3 (B03T3056–B03T3058, p-value < 1 × 10-10 ) and chromosome 9 (B09T8332–B09T8334, p-value 1 × 10-6 ). Based on the results of the simulated GAW14 data, the WA test statistic showed good performance and could narrow down the region containing the susceptibility locus. However, the strength of the signal depends on both the strength of the linkage disequilibrium and the heterozygosity of the linked marker.

Fine-scale mapping in case-control samples using locus scoring and haplotype-sharing methods

Both haplotype-based and locus-based methods have been proposed as the most powerful methods to employ when fine mapping by association. Although haplotype-based methods utilize more information, they may lose power as a result of overparameterization, given the large number of haplotypes possible over even a few loci. Recently methods have been developed that cluster haplotypes with similar structure in the hope that this reflects shared genealogical ancestry. The aim is to reduce the number of parameters while retaining the genotype information relating to disease susceptibility. We have compared several haplotype-based methods with locus-based methods. We utilized 2 regions (D2 and D4) simulated to be in linkage disequilibrium and to be associated with disease susceptibility, combining 5 replicates at a time to produce 4 datasets that were analyzed. We found little difference in the performance of the haplotype-based methods and the locus-based methods in this dataset.

Spatiotemporal problems with detecting and mapping mosaic fire regimes with coarse-resolution satellite data in savanna environments

Fire is a prominent disturbance factor and a major force of environmental change especially in the African savannas. The development of an accurate system to map and monitor fires on the African continent is a priority of numerous international research centers and programs. This effort has produced a flurry of research projects in recent years to detect and map areas affected by fires at the continental scale using coarse-resolution satellite imagery. The end product of these projects consists of weekly or monthly maps of burned area, several of which are available to the user community on the internet. It is argued here that the algorithms used to generate these products are designed to capture relatively large and contiguously burned areas and that the heterogeneous patterns of burn scars created by mosaic burning regimes pose a problem for current detection methodologies. Fine-scale burned area maps are generated using a series of Landsat ETM+imagery covering the 2002–2003 fire season for the study area in the savanna of southern Mali. These maps document a seasonal-mosaic pattern of burning in which burning begins early in the dry season and continues for several months ultimately affecting over 50% of the landscape. The majority of these fires burn relatively small areas producing a highly fragmented landscape pattern. A comparison of the fine scale maps with those from two widely available coarse-resolution products finds that the latter fail to detect approximately 90% of the burned area. A general argument is developed which suggests that the documented bias in the coarse resolution products is a function of low-resolution bias which derives from the fine-scale spatiotemporal pattern of burning not uncommon to savanna and other frequently burned environments. The study demonstrates how low-resolution bias can result in a significant underestimation of burned areas and/or a shift in the seasonal burned area profile in areas where mosaic burning occurs. The findings have implications for the development of broad-scale burned area detection algorithms as well as their applications to natural resource management and global environmental change research.

Benthic Mapping Using Sonar, Video Transects, and an Innovative Approach to Accuracy Assessment: A Characterization of Bottom Features in the Georgia Bight

Benthic maps provide the spatial framework for many science and management activities in coastal areas such as identification and protection of fish distributions and associated habitat as well as for monitoring changes in benthos and fish communities. To meet this need at Gray's Reef National Marine Sanctuary off the Georgia, U.S.A., coast, we created fine-scale benthic maps by visual interpretation of sonar imagery within a geographic information system. The major bottom types in the sanctuary—flat sand, rippled sand, hard bottom that is sparsely colonized with sessile invertebrates, and densely colonized hard bottom—were delineated through combined analysis of backscatter from side-scan sonar, bathymetry from multibeam sonar, scuba surveys, and video transects. Maps showed that unconsolidated sediments cover 75% of the bottom of this region; 8% occurs as flat sand plains with obvious burrowing and reworking of surface material by mobile benthic invertebrates, whereas 67% occurs as rippled sand without such fauna. The rest of the sanctuary consists of limestone bottom in two types of formations; either flat, sparsely colonized regions (25% of the sanctuary's total area) or as vertical ledges that are densely colonized with a diverse fauna of sessile invertebrates (<1%). Despite their limited area, these 0.5–2-m-tall ledge features harbor the majority of the sanctuary's biodiversity and biomass of both sessile invertebrates as well as ichthyofauna. A modified accuracy assessment procedure was used to account for spatial autocorrelation in the validation data and to separate thematic from positional accuracy. Overall thematic accuracy of maps is 95% for those areas of the map in which thematic accuracy and positional accuracy could be separated (87% of the mapped area). This fine-scale characterization provides a benthic inventory for a marine sanctuary and novel methods for mapping using sonar and accuracy assessment using transects.

The Impact of Using Related Individuals for Haplotype Reconstruction in Population Studies

Recent studies have highlighted the dangers of using haplotypes reconstructed directly from population data for a fine-scale mapping analysis. Family data may help resolve ambiguity, yet can be costly to obtain. This study is concerned with the following question: How much family data (if any) should be used to facilitate haplotype reconstruction in a population study? We conduct a simulation study to evaluate how changes in family information can affect the accuracy of haplotype frequency estimates and phase reconstruction. To reconstruct haplotypes, we introduce an EM-based algorithm that can efficiently accommodate unrelated individuals, parent-child trios, and arbitrarily large half-sib pedigrees. Simulations are conducted for a diverse set of haplotype frequency distributions, all of which have been previously published in empirical studies. A wide variety of important results regarding the effectiveness of using pedigree data in a population study are presented in a coherent, unified framework. Insight into the different properties of the haplotype frequency distribution that can influence experimental design is provided. We show that a preliminary estimate of the haplotype frequency distribution can be valuable in large population studies with fixed resources.

Characterization and mapping of Rpi1, a gene that confers dominant resistance to stalk rot in maize

The maize inbred lines 1145 (resistant) and Y331 (susceptible), and the F(1), F(2) and BC(1)F(1) populations derived from them were inoculated with the pathogen Pythium inflatum Matthews, which causes stalk rot in Zea mays. Field data revealed that the ratio of resistant to susceptible plants was 3:1 in the F(2) population, and 1:1 in the BC(1)F(1)population, indicating that the resistance to P. inflatum Matthews was controlled by a single dominant gene in the 1145xY331 cross. The gene that confers resistance to P. inflatum Matthews was designated Rpi1 for resistance to P. inflatum) according to the standard nomenclature for plant disease resistance genes. Fifty SSR markers from 10 chromosomes were first screened in the F(2) population to find markers linked to the Rpi1 gene. The results indicated that umc1702 and mmc0371 were both linked to Rpi1, placing the resistance gene on chromosome 4. RAPD (randomly amplified polymorphic DNA) markers were then tested in the F(2)population using bulked segregant analysis (BSA). Four RAPD products were found to show linkage to the Rpi1 gene. Then 27 SSR markers and 8 RFLP markers in the region encompassing Rpi1 were used for fine-scale mapping of the resistance gene. Two SSR markers and four RFLP markers were linked to the Rpi1 gene. Finally, the Rpi1 gene was mapped between the SSR markers bnlg1937 and agrr286 on chromosome 4, 1.6 cM away from the former and 4.1 cM distant from the latter. This is the first time that a dominant gene for resistance to maize stalk rot caused by P. inflatum Matthews has been mapped with molecular marker techniques.

Resolution and reproducibility of BOLD and perfusion functional MRI at 3.0 Tesla

Visual and somatosensory activation studies were performed on normal subjects to compare the spatial discrimination and reproducibility between functional MRI (fMRI) methods based on blood oxygen level-dependent (BOLD) and perfusion contrast. To allow simultaneous measurement of BOLD and perfusion contrast, a dedicated MRI acquisition technique was developed. Repeated experiments of sensory stimulation of single digits of the right hand showed an average variability of activation amplitude of 25% for BOLD data, and a significantly lower variability of 21% for perfusion data. No significant difference in the variability of the locus of activity was observed between the BOLD and perfusion data. In somatotopy experiments, digits II and V were subjected to passive sensory stimulation. Both the BOLD and perfusion data showed substantial overlap in the activation patterns from the two digits. In a retinotopy study, two stimuli were alternated to excite different patches of V1. Again there was substantial overlap between the activation patterns from both stimuli, although the perfusion performed somewhat better than the BOLD method. Particularly for the visual studies, the overlap in activation patterns was more than expected based on the fine-scale retinotopic mapping of cortical activity, suggesting that both BOLD and perfusion contrast mechanisms contribute substantially to the point-spread function (PSF).

A Continuous Smooth Map of Space in the Primary Visual Cortex of the Common Marmoset

We examined the fine-scale mapping of the visual world within the primary visual cortex of the marmoset monkey (Callithrix jacchus) using differential optical imaging. We stimulated two sets of complementary stripe-like locations in turn, subtracting them to generate the cortical representations of continuous bands of visual space. Rotating this stimulus configuration makes it possible to map different spatial axes within the primary visual cortex. In a similar manner, shifting the stimulated locations between trials makes it possible to map retinotopy at an even finer scale. Using these methods we found no evidence of any local anisotropies or distortions in the cortical representation of visual space. This is despite the fact that orientation preference is mapped in a discontinuous manner across the surface of marmoset V1. Overall, our results indicate that space is mapped in a continuous and smooth manner in the primary visual cortex of the common marmoset.

Capturing spatial variability of soil and litter properties in a forest stand by landform segmentation procedures

Most conventional land surveys, maps, and databases provide relatively coarse-scale spatial information. Landform segmentation, a branch of Digital Terrain Analysis that groups similar topographic attributes into spatial units, may provide an efficient, quantitative approach for modeling spatial variability at smaller scales relevant to land planners, managers, and ecologists. Landform segmentation was used in a deciduous forest stand on the Oak Ridges Moraine in southern Ontario, Canada in order to examine effects of topography on soil and stand properties used in indices of soil quality and stand productivity. Significant differences were recorded between the LEC spatial units in what is conventionally considered to be a homogenous forest stand on one soil unit. The largest spatial differences were those associated with the movement of water and soil particles from divergent shoulder positions to level or convergent landforms. Spatial pattern of litter was largely influenced by the amount of downed woody debris and downed trees at the site, rather than by differences in topography, and acted to impede down slope movement of material. Fine-scale spatial maps of the results were constructed to demonstrate improvements over conventional sources of soil and land information such as coarse-resolution 2-D maps.

Experimental designs for reliable detection of linkage disequilibrium in unstructured random population association studies.

A method is given for design of experiments to detect associations (linkage disequilibrium) in a random population between a marker and a quantitative trait locus (QTL), or gene, with a given strength of evidence, as defined by the Bayes factor. Using a version of the Bayes factor that can be linked to the value of an F-statistic with an existing deterministic power calculation makes it possible to rapidly evaluate a comprehensive range of scenarios, demonstrating the feasibility, or otherwise, of detecting genes of small effect. The Bayes factor is advocated for use in determining optimal strategies for selecting candidate genes for further testing or applications. The prospects for fine-scale mapping of QTL are reevaluated in this framework. We show that large sample sizes are needed to detect small-effect genes with a respectable-sized Bayes factor, and to have good power to detect a QTL allele at low frequency it is necessary to have a marker with similar allele frequency near the gene.

Fine-scale structural variation of the human genome

Inversions, deletions and insertions are important mediators of disease and disease susceptibility. We systematically compared the human genome reference sequence with a second genome (represented by fosmid paired-end sequences) to detect intermediate-sized structural variants >8 kb in length. We identified 297 sites of structural variation: 139 insertions, 102 deletions and 56 inversion breakpoints. Using combined literature, sequence and experimental analyses, we validated 112 of the structural variants, including several that are of biomedical relevance. These data provide a fine-scale structural variation map of the human genome and the requisite sequence precision for subsequent genetic studies of human disease.