Biomedical subjects

Stephen Kresovich

Publications and source records attributed to Stephen Kresovich.

13 recordsLinked to original sources

PubMed2006

Challenges of detecting directional selection after a bottleneck: lessons from Sorghum bicolor.

Multilocus surveys of sequence variation can be used to identify targets of directional selection, which are expected to have reduced levels of variation. Following a population bottleneck, the signal of directional selection may be hard to detect because many loci may have low variation by chance and the frequency spectrum of variation may be perturbed in ways that resemble the effects of selection. Cultivated Sorghum bicolor contains a subset of the genetic diversity found in its wild ancestor(s) due to the combined effects of a domestication bottleneck and human selection on traits associated with agriculture. As a framework for distinguishing between the effects of demography and selection, we sequenced 204 loci in a diverse panel of 17 cultivated S. bicolor accessions. Genomewide patterns of diversity depart strongly from equilibrium expectations with regard to the variance of the number of segregating sites, the site frequency spectrum, and haplotype configuration. Furthermore, gene genealogies of most loci with an excess of low frequency variants and/or an excess of segregating sites do not show the characteristic signatures of directional and diversifying selection, respectively. A simple bottleneck model provides an improved but inadequate fit to the data, suggesting the action of other population-level factors, such as population structure and migration. Despite a known history of recent selection, we find little evidence for directional selection, likely due to low statistical power and lack of an appropriate null model.

Agriculture↗

PubMed2006

Panzea: a database and resource for molecular and functional diversity in the maize genome.

Serving as a community resource, Panzea (http://www.panzea.org) is the bioinformatics arm of the Molecular and Functional Diversity in the Maize Genome project. Maize, a classical model for genetic studies, is an important crop species and also the most diverse crop species known. On average, two randomly chosen maize lines have one single-nucleotide polymorphism every approximately 100 bp; this divergence is roughly equivalent to the differences between humans and chimpanzees. This exceptional genotypic diversity underlies the phenotypic diversity maize needs to be cultivated in a wide range of environments. The Molecular and Functional Diversity in the Maize Genome project aims to understand how selection has shaped molecular diversity in maize and then relate molecular diversity to functional phenotypic variation. The project will screen 4000 loci for the signature of selection and create a wide range of maize and maize-teosinte mapping populations. These populations will be genotyped and phenotyped, permitting high-power and high-resolution dissection of the traits and relating the molecular diversity to functional variation. Panzea provides access to the genotype, phenotype and polymorphism data produced by the project through user-friendly web-based database searches and data retrieval/visualization tools, as well as a wide variety of information and services related to maize diversity.

Chromosome Mapping↗

PubMed2005

A unified mixed-model method for association mapping that accounts for multiple levels of relatedness.

As population structure can result in spurious associations, it has constrained the use of association studies in human and plant genetics. Association mapping, however, holds great promise if true signals of functional association can be separated from the vast number of false signals generated by population structure. We have developed a unified mixed-model approach to account for multiple levels of relatedness simultaneously as detected by random genetic markers. We applied this new approach to two samples: a family-based sample of 14 human families, for quantitative gene expression dissection, and a sample of 277 diverse maize inbred lines with complex familial relationships and population structure, for quantitative trait dissection. Our method demonstrates improved control of both type I and type II error rates over other methods. As this new method crosses the boundary between family-based and structured association samples, it provides a powerful complement to currently available methods for association mapping.

Gene Expression↗

PubMed2005

Equilibrium processes cannot explain high levels of short- and medium-range linkage disequilibrium in the domesticated grass Sorghum bicolor.

Patterns of linkage disequilibrium (LD) are of interest because they provide evidence of both equilibrium (e.g., mating system or long-term population structure) and nonequilibrium (e.g., demographic or selective) processes, as well as because of their importance in strategies for identifying the genetic basis of complex phenotypes. We report patterns of short and medium range (up to 100 kb) LD in six unlinked genomic regions in the partially selfing domesticated grass, Sorghum bicolor. The extent of allelic associations in S. bicolor, as assessed by pairwise measures of LD, is higher than in maize but lower than in Arabidopsis, in qualitative agreement with expectations based on mating system. Quantitative analyses of the population recombination parameter, rho, however, based on empirical estimates of rates of recombination, mutation, and self-pollination, show that LD is more extensive than expected under a neutral equilibrium model. The disparity between rho and the population mutation parameter, , is similar to that observed in other species whose population history appears to be complex. From a practical standpoint, these results suggest that S. bicolor is well suited for association studies using reasonable numbers of markers, since LD typically extends at least several kilobases but has largely decayed by 15 kb.

Chromosomes, Artificial, Bacterial↗

PubMed2005

Identification and characterization of regions of the rice genome associated with broad-spectrum, quantitative disease resistance.

Much research has been devoted to understanding the biology of plant-pathogen interactions. The extensive genetic analysis of disease resistance in rice, coupled with the sequenced genome and genomic resources, provides the opportunity to seek convergent evidence implicating specific chromosomal segments and genes in the control of resistance. Published data on quantitative and qualitative disease resistance in rice were synthesized to evaluate the distributions of and associations among resistance loci. Quantitative trait loci (QTL) for resistance to multiple diseases and qualitative resistance loci (R genes) were clustered in the rice genome. R genes and their analogs of the nucleotide binding site-leucine-rich repeat class and genes identified on the basis of differential representation in disease-related EST libraries were significantly associated with QTL. Chromosomal segments associated with broad-spectrum quantitative disease resistance (BS-QDR) were identified. These segments contained numerous positional candidate genes identified on the basis of a range of criteria, and groups of genes belonging to two defense-associated biochemical pathways were found to underlie one BS-QDR region. Genetic dissection of disease QTL confidence intervals is needed to reduce the number of positional candidate genes for further functional analysis. This study provides a framework for future investigations of disease resistance in rice and related crop species.

Blotting, Northern↗

PubMed2005

An analysis of genetic diversity across the maize genome using microsatellites.

How domestication bottlenecks and artificial selection shaped the amount and distribution of genetic variation in the genomes of modern crops is poorly understood. We analyzed diversity at 462 simple sequence repeats (SSRs) or microsatellites spread throughout the maize genome and compared the diversity observed at these SSRs in maize to that observed in its wild progenitor, teosinte. The results reveal a modest genome-wide deficit of diversity in maize relative to teosinte. The relative deficit of diversity is less for SSRs with dinucleotide repeat motifs than for SSRs with repeat motifs of more than two nucleotides, suggesting that the former with their higher mutation rate have partially recovered from the domestication bottleneck. We analyzed the relationship between SSR diversity and proximity to QTL for domestication traits and observed no relationship between these factors. However, we did observe a weak, although significant, spatial correlation for diversity statistics among SSRs within 2 cM of one another, suggesting that SSR diversity is weakly patterned across the genome. Twenty-four of 462 SSRs (5%) show some evidence of positive selection in maize under multiple tests. Overall, the pattern of genetic diversity at maize SSRs can be explained largely by a bottleneck effect with a smaller effect from selection.

DNA, Plant↗

PubMed2005

Maize association population: a high-resolution platform for quantitative trait locus dissection.

Crop improvement and the dissection of complex genetic traits require germplasm diversity. Although this necessary phenotypic variability exists in diverse maize, most research is conducted using a small subset of inbred lines. An association population of 302 lines is now available--a valuable research tool that captures a large proportion of the alleles in cultivated maize. Provided that appropriate statistical models correcting for population structure are included, this tool can be used in association analyses to provide high-resolution evaluation of multiple alleles. This study describes the population structure of the 302 lines, and investigates the relationship between population structure and various measures of phenotypic and breeding value. On average, our estimates of population structure account for 9.3% of phenotypic variation, roughly equivalent to a major quantitative trait locus (QTL), with a high of 35%. Inclusion of population structure in association models is critical to meaningful analyses. This new association population has the potential to identify QTL with small effects, which will aid in dissecting complex traits and in planning future projects to exploit the rich diversity present in maize.

Chromosome Mapping↗

PubMed2004

Genetic diversity of peanut (Arachis hypogaea L.) and its wild relatives based on the analysis of hypervariable regions of the genome.

BACKGROUND: The genus Arachis is native to a region that includes Central Brazil and neighboring countries. Little is known about the genetic variability of the Brazilian cultivated peanut (Arachis hypogaea, genome AABB) germplasm collection at the DNA level. The understanding of the genetic diversity of cultivated and wild species of peanut (Arachis spp.) is essential to develop strategies of collection, conservation and use of the germplasm in variety development. The identity of the ancestor progenitor species of cultivated peanut has also been of great interest. Several species have been suggested as putative AA and BB genome donors to allotetraploid A. hypogaea. Microsatellite or SSR (Simple Sequence Repeat) markers are co-dominant, multiallelic, and highly polymorphic genetic markers, appropriate for genetic diversity studies. Microsatellite markers may also, to some extent, support phylogenetic inferences. Here we report the use of a set of microsatellite markers, including newly developed ones, for phylogenetic inferences and the analysis of genetic variation of accessions of A. hypogea and its wild relatives. RESULTS: A total of 67 new microsatellite markers (mainly TTG motif) were developed for Arachis. Only three of these markers, however, were polymorphic in cultivated peanut. These three new markers plus five other markers characterized previously were evaluated for number of alleles per locus and gene diversity using 60 accessions of A. hypogaea. Genetic relationships among these 60 accessions and a sample of 36 wild accessions representative of section Arachis were estimated using allelic variation observed in a selected set of 12 SSR markers. Results showed that the Brazilian peanut germplasm collection has considerable levels of genetic diversity detected by SSR markers. Similarity groups for A. hypogaea accessions were established, which is a useful criteria for selecting parental plants for crop improvement. Microsatellite marker transferability was up to 76% for species of the section Arachis, but only 45% for species from the other eight Arachis sections tested. A new marker (Ah-041) presented a 100% transferability and could be used to classify the peanut accessions in AA and non-AA genome carriers. CONCLUSION: The level of polymorphism observed among accessions of A. hypogaea analyzed with newly developed microsatellite markers was low, corroborating the accumulated data which show that cultivated peanut presents a relatively reduced variation at the DNA level. A selected panel of SSR markers allowed the classification of A. hypogaea accessions into two major groups. The identification of similarity groups will be useful for the selection of parental plants to be used in breeding programs. Marker transferability is relatively high between accessions of section Arachis. The possibility of using microsatellite markers developed for one species in genetic evaluation of other species greatly reduces the cost of the analysis, since the development of microsatellite markers is still expensive and time consuming. The SSR markers developed in this study could be very useful for genetic analysis of wild species of Arachis, including comparative genome mapping, population genetic structure and phylogenetic inferences among species.

Alleles↗

PubMed2004

Molecular evolution of the phytochrome gene family in sorghum: changing rates of synonymous and replacement evolution.

The photoreceptor phytochromes, encoded by a small gene family, are responsible for controlling the expression of a number of light-responsive genes and photomorphogenic events, including agronomically important phenotypes such as flowering time and shade-avoidance behavior. The understanding and control of flowering time are particularly important goals in sorghum cultivar development for diverse environments, and naturally occurring variation in the phytochrome genes might prove useful in breeding programs. Also of interest is whether variation observed at the phytochrome loci in domesticated sorghum, or in particular races, is a result of human selection. Population genetic studies can reveal evidence of such selection in patterns of polymorphism and divergence. In this study we report a population genetic analysis of the PHY gene family in Sorghum bicolor (L.) Moench in a diverse panel including both cultivated and wild accessions. We show that the level of nucleotide variation in all gene family members is about half the average for this species, consistent with purifying selection acting on these loci. However, the rate of amino acid substitution is accelerated at PHYC compared to the other two loci. In comparisons to a closely related sorghum species, PHYC shows a pattern of intermediate frequency amino acid changes that differ from the patterns observed in comparisons across longer evolutionary distances. There is also a departure from expected patterns of polymorphism and divergence at synonymous sites in PHYC, although the data do not fit a simple model of directional or diversifying selection. Cultivated sorghum has a level of variation similar to that of wild relatives (ssp. verticilliflorum), but many polymorphisms are subspecies-specific, including several amino acid variants.

Amino Acid Sequence↗

PubMed2004

Comparative population genetics of the panicoid grasses: sequence polymorphism, linkage disequilibrium and selection in a diverse sample of sorghum bicolor.

Levels of genetic variation and linkage disequilibrium (LD) are critical factors in association mapping methods as well as in identification of loci that have been targets of selection. Maize, an outcrosser, has a high level of sequence variation and a limited extent of LD. Sorghum, a closely related but largely self-pollinating panicoid grass, is expected to have higher levels of LD. As a first step in estimation of population genetic parameters in sorghum, we surveyed 27 diverse S. bicolor accessions for sequence variation at a total of 29,186 bp in 95 short regions derived from genetically mapped RFLPs located throughout the genome. Consistent with its higher level of inbreeding, the extent of LD is at least severalfold greater in sorghum than in maize. Total sequence variation in sorghum is about fourfold lower than that in maize, while synonymous variation is fivefold lower, suggesting a smaller effective population size in sorghum. Because we surveyed a species-wide sample, the mating system, which primarily affects population-level diversity, may not be primarily responsible for this difference. Comparisons of polymorphism and divergence suggest that both directional and diversifying selection have played important roles in shaping variation in the sorghum genome.

Genes, Plant↗

PubMed2003

High resolution genetic mapping and candidate gene identification at the xa5 locus for bacterial blight resistance in rice ( Oryza sativa L.).

The xa5 resistance gene from rice provides recessive, race-specific resistance to bacterial blight of rice caused by the pathogen Xanthomonas oryzae pv oryzae. A high-resolution genetic map of the chromosomal region surrounding xa5 was developed by placing 44 DNA markers on the distal end of rice chromosome 5. The basis for mapping was a PCR-based screening of 1,016 F(2) individuals derived from a cross between a near-isogenic line (NIL) and its corresponding recurrent parent to identify recombinants in the region. Recombinant F(2) individuals were progeny tested using F(3) families inoculated with the Philippine strain PXO 61 of bacterial blight pathogen. The xa5 gene was mapped to a 0.5-cM interval between the markers RS7 and RM611, which spanned an interval of approximately 70 kb and contained a total of 11 open reading frames. Sequence data for the locus was generated from an Indica (the IR24 isoline, IRBB21) BAC covering part of the region and compared to other overlapping Indica (cv 93-11) and Japonica (cv Nipponbare) sequences. Candidate-gene analysis revealed that a basal transcription factor (TFIIa), an ABC transporter, a tRNA synthase, a MAP kinase and a cysteine protease, as well as four unknown, hypothetical or putative proteins, are encoded at the locus and could be potential candidates for the resistance gene product. The mechanism by which these genes could provide recessive, race-specific resistance will be elucidated by map-based cloning of the xa5 gene.

Chromosomes, Artificial, Bacterial↗

PubMed2003

A high-density genetic recombination map of sequence-tagged sites for sorghum, as a framework for comparative structural and evolutionary genomics of tropical grains and grasses.

We report a genetic recombination map for Sorghum of 2512 loci spaced at average 0.4 cM ( approximately 300 kb) intervals based on 2050 RFLP probes, including 865 heterologous probes that foster comparative genomics of Saccharum (sugarcane), Zea (maize), Oryza (rice), Pennisetum (millet, buffelgrass), the Triticeae (wheat, barley, oat, rye), and Arabidopsis. Mapped loci identify 61.5% of the recombination events in this progeny set and reveal strong positive crossover interference acting across intervals of </=50 cM. Significant variations in DNA marker density are related to possible centromeric regions and to probable chromosome structural rearrangements between Sorghum bicolor and S. propinquum, but not to variation in levels of intraspecific allelic richness. While cDNA and genomic clones are similarly distributed across the genome, SSR-containing clones show different abundance patterns. Rapidly evolving hypomethylated DNA may contribute to intraspecific genomic differentiation. Nonrandom distribution patterns of multiple loci detected by 357 probes suggest ancient chromosomal duplication followed by extensive rearrangement and gene loss. Exemplifying the value of these data for comparative genomics, we support and extend prior findings regarding maize-sorghum synteny-in particular, 45% of comparative loci fall outside the inferred colinear/syntenic regions, suggesting that many small rearrangements have occurred since maize-sorghum divergence. These genetically anchored sequence-tagged sites will foster many structural, functional and evolutionary genomic studies in major food, feed, and biomass crops.

Biological Evolution↗

PubMed2003

Population structure and its effect on haplotype diversity and linkage disequilibrium surrounding the xa5 locus of rice (Oryza sativa L.).

To assess the usefulness of linkage disequilibrium mapping in an autogamous, domesticated species, we have characterized linkage disequilibrium in the candidate region for xa5, a recessive gene conferring race-specific resistance to bacterial blight in rice. This trait and locus have good mapping information, a tractable phenotype, and available sequence data, but no cloned gene. We sampled 13 short segments from the 70-kb candidate region in 114 accessions of Oryza sativa. Five additional segments were sequenced from the adjacent 45-kb region in resistant accessions to estimate the distance at which linkage disequilibrium decays. The data show significant linkage disequilibrium between sites 100 kb apart. The presence of the xa5 resistant reaction in two ecotypes and in accessions with different haplotypes in the candidate region may indicate multiple origins or genetic heterogeneity for resistance. In addition, genetic differentiation between ecotypes emphasizes the need for controlling for population structure in the design of linkage disequilibrium studies in rice.

Genetic Variation↗