Leonid Kruglyak

Measuring differential gene expression by short read sequencing: quantitative comparison to 2-channel gene expression microarrays (2009)

Bloom, Joshua S, Khan, Zia, Kruglyak, Leonid, Singh, Mona, Caudy, Amy A

Abstract Background High-throughput cDNA synthesis and sequencing of poly(A)-enriched RNA is rapidly emerging as a technology competing to replace microarrays as a quantitative platform for measuring...

A practical algorithm for finding maximal exact matches in large sequence datasets using sparse suffix arrays (2009)

Khan, Zia, Bloom, Joshua S., Kruglyak, Leonid, Singh, Mona

Motivation: High-throughput sequencing technologies place ever increasing demands on existing algorithms for sequence analysis. Algorithms for computing maximal exact matches (MEMs) between sequences...

Gene–Environment Interaction in Yeast Gene Expression (2008)

Erin N. Smith, Leonid Kruglyak

The effects of genetic variants on phenotypic traits often depend on environmental and physiological conditions, but such gene–environment interactions are poorly understood. Recently developed...

Rapid Multipoint Linkage Analysis of Recessive Traits in Nuclear Families, including Homozygosity Mapping (2007)

Leonid Kruglyak, Mark J. Daly, Eric S. Lander, Eric S. L

this paper allows very rapid multipoint likelihood calculation in nuclear families (with or without parental consanguinity), and the accompanying software package makes multipoint mapping feasible in...

Allele Frequency Matching Between SNPs Reveals an Excess of Linkage Disequilibrium in Genic Regions of the Human Genome (2006)

Michael A. Eberle, Mark J. Rieder, Leonid Kruglyak, Deborah A. Nickerson

Significant interest has emerged in mapping genetic susceptibility for complex traits through whole-genome association studies. These studies rely on the extent of association, i.e., linkage...

Frequency-Matching SNPs Reveals Extended Linkage Disequilibrium in Genic Regions (2006)

Michael A Eberle, Mark J Rieder, Leonid Kruglyak, Deborah A. Nickerson

Significant interest has emerged in mapping genetic susceptibility for complex traits through whole-genome association studies. These studies rely on the extent of association, i.e. linkage...

Telomere Length as a Quantitative Trait: Genome-Wide Survey and Genetic Mapping of Telomere Length-Control Genes in Yeast (2006)

Tonibelle Gatbonton, Maria Imbesi, Melisa Nelson, Joshua M. Akey, Douglas M. Ruderfer, Leonid Kruglyak, ...

Telomere length-variation in deletion strains of Saccharomyces cerevisiae was used to identify genes and pathways that regulate telomere length. We found 72 genes that when deleted confer short...

Multiple Locus Linkage Analysis of Genomewide Expression in Yeast (2005)

John D. Storey, Joshua M. Akey, Leonid Kruglyak

Complex traits are frequently under control of multiple loci. This new method simultaneously maps multiple gene expression quantitative trait loci and assesses their significance within Saccharomyces...

Multiple Locus Linkage Analysis of Genomewide Expression in Yeast (2005)

John D. Storey, Joshua M. Akey, Leonid Kruglyak

With the ability to measure thousands of related phenotypes from a single biological sample, it is now feasible to genetically dissect systems-level biological phenomena. The genetics of...

Local Regulatory Variation in Saccharomyces cerevisiae (2005)

James Ronald, Rachel B. Brem, Jacqueline Whittle, Leonid Kruglyak

Naturally occurring sequence variation that affects gene expression is an important source of phenotypic differences among individuals within a species. We and others have previously shown that such...

Simultaneous genotyping, gene-expression measurement, and detection of allele-specific expression with oligonucleotide arrays (2005)

Ronald, James, Akey, Joshua M., Whittle, Jacqueline, Smith, Erin N., Yvert, Gael, Kruglyak, Leonid

Oligonucleotide microarrays provide a high-throughput method for exploring genomes. In addition to their utility for gene-expression analysis, oligonucleotide-expression arrays have also been used to...

Population History and Natural Selection Shape Patterns of Genetic Variation in 132 Genes (2004)

Joshua M. Akey, Michael A. Eberle, Mark J. Rieder, Christopher S. Carlson, Mark D. Shriver, Deborah A. Nickerson, ...

An analysis of 132 human genes suggests that the migration of modern humans out of Africa into new environments was accompanied by genetic adaptations to emergent selective forces.

Population History and Natural Selection Shape Patterns of Genetic Variation in 132 Genes (2004)

Joshua M. Akey, Michael A. Eberle, Mark J. Rieder, Christopher S. Carlson, Mark D. Shriver, Deborah A. Nickerson, ...

Identifying regions of the human genome that have been targets of natural selection will provide important insights into human evolutionary history and may facilitate the identification of complex...

Extensive and breed-specific linkage disequilibrium in Canis familiaris (2004)

Sutter, Nathan B., Eberle, Michael A., Parker, Heidi G., Pullar, Barbara J., Kirkness, Ewen F., Kruglyak, Leonid, ...

The 156 breeds of registered dogs in the United States offer a unique opportunity to map genes important in disease susceptibility, morphology, and behavior. Linkage disequilibrium (LD) is of current...

Extensive and breed-specific linkage disequilibrium in Canis familiaris (2004)

Sutter, Nathan B., Eberle, Michael A., Parker, Heidi G., Pullar, Barbara J., Kirkness, Ewen F., Kruglyak, Leonid, ...

The 156 breeds of registered dogs in the United States offer a unique opportunity to map genes important in disease susceptibility, morphology, and behavior. Linkage disequilibrium (LD) is of current...

Precise gene localization by phenotypic assay of radiation hybrid cells

Rasko, John E. J., Battini, Jean-Luc, Kruglyak, Leonid, Cox, David R., Miller, A. Dusty

A high resolution map of the human genome previously has been constructed by using the G3 panel of human/hamster radiation hybrid cell lines and >15,000 unique human genetic markers. By determining...

Linkage of a neurophysiological deficit in schizophrenia to a chromosome 15 locus

Freedman, Robert, Coon, Hilary, Myles-Worsley, Marina, Orr-Urtreger, Avi, Olincy, Ann, Davis, Ashley, ...

Inheritance of a defect in a neuronal mechanism that regulates response to auditory stimuli was studied in nine families with multiple cases of schizophrenia. The defect, a decrease in the normal...

Population History and Natural Selection Shape Patterns of Genetic Variation in 132 Genes

Akey, Joshua M, Eberle, Michael A, Rieder, Mark J, Carlson, Christopher S, Shriver, Mark D, Nickerson, Deborah A, ...

Identifying regions of the human genome that have been targets of natural selection will provide important insights into human evolutionary history and may facilitate the identification of complex...

Extensive and breed-specific linkage disequilibrium in Canis familiaris

Sutter, Nathan B., Eberle, Michael A., Parker, Heidi G., Pullar, Barbara J., Kirkness, Ewen F., Kruglyak, Leonid, ...

The 156 breeds of registered dogs in the United States offer a unique opportunity to map genes important in disease susceptibility, morphology, and behavior. Linkage disequilibrium (LD) is of current...

Simultaneous genotyping, gene-expression measurement, and detection of allele-specific expression with oligonucleotide arrays

Ronald, James, Akey, Joshua M., Whittle, Jacqueline, Smith, Erin N., Yvert, Gael, Kruglyak, Leonid

Oligonucleotide microarrays provide a high-throughput method for exploring genomes. In addition to their utility for gene-expression analysis, oligonucleotide-expression arrays have also been used to...

The landscape of genetic complexity across 5,700 gene expression traits in yeast

Brem, Rachel B., Kruglyak, Leonid

Many studies have identified quantitative trait loci (QTLs) that contribute to continuous variation in heritable traits of interest. However, general principles regarding the distribution of QTL...

Multiple Locus Linkage Analysis of Genomewide Expression in Yeast

Storey, John D, Akey, Joshua M, Kruglyak, Leonid

With the ability to measure thousands of related phenotypes from a single biological sample, it is now feasible to genetically dissect systems-level biological phenomena. The genetics of...

Local Regulatory Variation in Saccharomyces cerevisiae

Ronald, James, Brem, Rachel B, Whittle, Jacqueline, Kruglyak, Leonid

Naturally occurring sequence variation that affects gene expression is an important source of phenotypic differences among individuals within a species. We and others have previously shown that such...

Sequence Variation and Linkage Disequilibrium in the Human T-Cell Receptor β (TCRB) Locus

Subrahmanyan, Lakshman, Eberle, Michael A., Clark, Andrew G., Kruglyak, Leonid, Nickerson, Deborah A.

The T-cell receptor (TCR) plays a central role in the immune system, and >90% of human T cells present a receptor that consists of the α TCR subunit (TCRA) and the β subunit (TCRB). Here we report...

Lower-Than-Expected Linkage Disequilibrium between Tightly Linked Markers in Humans Suggests a Role for Gene Conversion

Ardlie, Kristin, Liu-Cordero, Shau Neen, Eberle, Michael A., Daly, Mark, Barrett, Jeff, Winchester, Ellen, ...

Understanding the pattern of linkage disequilibrium (LD) in the human genome is important both for successful implementation of disease-gene mapping approaches and for inferences about human...

Efficient Multipoint Linkage Analysis through Reduction of Inheritance Space

Markianos, Kyriacos, Daly, Mark J., Kruglyak, Leonid

Computational constraints currently limit exact multipoint linkage analysis to pedigrees of moderate size. We introduce new algorithms that allow analysis of larger pedigrees by reducing the time and...

Exact Multipoint Quantitative-Trait Linkage Analysis in Pedigrees by Variance Components

Pratt, Stephen C., Daly, Mark J., Kruglyak, Leonid

Methods based on variance components are powerful tools for linkage analysis of quantitative traits, because they allow simultaneous consideration of all pedigree members. The central idea is to...

Full-Genome Scan for Linkage in 50 Families Segregating the Bipolar Affective Disease Phenotype

Friddle, Carl, Koskela, Rebecca, Ranade, Koustubh, Hebert, Joan, Cargill, Michele, Clark, Chris D., ...

A genome scan of ∼12-cM initial resolution was done on 50 of a set of 51 carefully ascertained unilineal multiplex families segregating the bipolar affective disorder phenotype. In addition to...

Genetic interactions between polymorphisms that affect gene expression in yeast

Brem, Rachel B., Storey, John D., Whittle, Jacqueline, Kruglyak, Leonid

Interactions between polymorphisms at different quantitative trait loci (QTLs) are thought to contribute to the genetics of many traits, and can dramatically impact the power of genetic studies to...

Telomere Length as a Quantitative Trait: Genome-Wide Survey and Genetic Mapping of Telomere Length-Control Genes in Yeast

Gatbonton, Tonibelle, Imbesi, Maria, Nelson, Melisa, Akey, Joshua M, Ruderfer, Douglas M, Kruglyak, Leonid, ...

Telomere length-variation in deletion strains of Saccharomyces cerevisiae was used to identify genes and pathways that regulate telomere length. We found 72 genes that when deleted confer short...

Allele Frequency Matching Between SNPs Reveals an Excess of Linkage Disequilibrium in Genic Regions of the Human Genome

Eberle, Michael A, Rieder, Mark J, Kruglyak, Leonid, Nickerson, Deborah A

Significant interest has emerged in mapping genetic susceptibility for complex traits through whole-genome association studies. These studies rely on the extent of association, i.e., linkage...

Precise gene localization by phenotypic assay of radiation hybrid cells

Rasko, John E. J., Battini, Jean-Luc, Kruglyak, Leonid, Cox, David R., Miller, A. Dusty

A high resolution map of the human genome previously has been constructed by using the G3 panel of human/hamster radiation hybrid cell lines and >15,000 unique human genetic markers. By determining...

Linkage of a neurophysiological deficit in schizophrenia to a chromosome 15 locus

Freedman, Robert, Coon, Hilary, Myles-Worsley, Marina, Orr-Urtreger, Avi, Olincy, Ann, Davis, Ashley, ...

Inheritance of a defect in a neuronal mechanism that regulates response to auditory stimuli was studied in nine families with multiple cases of schizophrenia. The defect, a decrease in the normal...

A New Susceptibility Locus for Autosomal Dominant Pancreatic Cancer Maps to Chromosome 4q32-34

Eberle, Michael A., Pfützer, Roland, Pogue-Geile, Kay L., Bronner, Mary P., Crispin, David, Kimmey, Michael B., ...

Pancreatic cancer is the fifth leading cause of cancer death in the United States. Nearly every person diagnosed with pancreatic cancer will die from it, usually in

Population History and Natural Selection Shape Patterns of Genetic Variation in 132 Genes

Akey, Joshua M, Eberle, Michael A, Rieder, Mark J, Carlson, Christopher S, Shriver, Mark D, Nickerson, Deborah A, ...

Identifying regions of the human genome that have been targets of natural selection will provide important insights into human evolutionary history and may facilitate the identification of complex...

Extensive and breed-specific linkage disequilibrium in Canis familiaris

Sutter, Nathan B., Eberle, Michael A., Parker, Heidi G., Pullar, Barbara J., Kirkness, Ewen F., Kruglyak, Leonid, ...

The 156 breeds of registered dogs in the United States offer a unique opportunity to map genes important in disease susceptibility, morphology, and behavior. Linkage disequilibrium (LD) is of current...

Simultaneous genotyping, gene-expression measurement, and detection of allele-specific expression with oligonucleotide arrays

Ronald, James, Akey, Joshua M., Whittle, Jacqueline, Smith, Erin N., Yvert, Gael, Kruglyak, Leonid

Oligonucleotide microarrays provide a high-throughput method for exploring genomes. In addition to their utility for gene-expression analysis, oligonucleotide-expression arrays have also been used to...

The landscape of genetic complexity across 5,700 gene expression traits in yeast

Brem, Rachel B., Kruglyak, Leonid

Many studies have identified quantitative trait loci (QTLs) that contribute to continuous variation in heritable traits of interest. However, general principles regarding the distribution of QTL...

A 3.9-Centimorgan-Resolution Human Single-Nucleotide Polymorphism Linkage Map and Screening Set

Matise, Tara C., Sachidanandam, Ravi, Clark, Andrew G., Kruglyak, Leonid, Wijsman, Ellen, Kakol, Jerzy, ...

Recent advances in technologies for high-throughout single-nucleotide polymorphism (SNP)–based genotyping have improved efficiency and cost so that it is now becoming reasonable to consider the use...

Multiple Locus Linkage Analysis of Genomewide Expression in Yeast

Storey, John D, Akey, Joshua M, Kruglyak, Leonid

With the ability to measure thousands of related phenotypes from a single biological sample, it is now feasible to genetically dissect systems-level biological phenomena. The genetics of...

Selecting a Maximally Informative Set of Single-Nucleotide Polymorphisms for Association Analyses Using Linkage Disequilibrium

Carlson, Christopher S., Eberle, Michael A., Rieder, Mark J., Yi, Qian, Kruglyak, Leonid, Nickerson, Deborah A.

Common genetic polymorphisms may explain a portion of the heritable risk for common diseases. Within candidate genes, the number of common polymorphisms is finite, but direct assay of all existing...

Haplotype Diversity across 100 Candidate Genes for Inflammation, Lipid Metabolism, and Blood Pressure Regulation in Two Populations

Crawford, Dana C., Carlson, Christopher S., Rieder, Mark J., Carrington, Dana P., Yi, Qian, Smith, Joshua D., ...

Recent studies have suggested that a significant fraction of the human genome is contained in blocks of strong linkage disequilibrium, ranging from ∼5 to >100 kb in length, and that within these...

Sequence-Based Linkage Analysis

Furman, Itay, Rieder, Mark J., Da Ponte, Suzanne, Carrington, Dana P., Nickerson, Deborah A., Kruglyak, Leonid, ...

The rapid decrease in the cost of DNA sequencing will enable its use for novel applications. Here, we investigate the use of DNA sequencing for simultaneous discovery and genotyping of polymorphisms...

Local Regulatory Variation in Saccharomyces cerevisiae

Ronald, James, Brem, Rachel B, Whittle, Jacqueline, Kruglyak, Leonid

Naturally occurring sequence variation that affects gene expression is an important source of phenotypic differences among individuals within a species. We and others have previously shown that such...

Sequence Variation and Linkage Disequilibrium in the Human T-Cell Receptor β (TCRB) Locus

Subrahmanyan, Lakshman, Eberle, Michael A., Clark, Andrew G., Kruglyak, Leonid, Nickerson, Deborah A.

The T-cell receptor (TCR) plays a central role in the immune system, and >90% of human T cells present a receptor that consists of the α TCR subunit (TCRA) and the β subunit (TCRB). Here we report...

Lower-Than-Expected Linkage Disequilibrium between Tightly Linked Markers in Humans Suggests a Role for Gene Conversion

Ardlie, Kristin, Liu-Cordero, Shau Neen, Eberle, Michael A., Daly, Mark, Barrett, Jeff, Winchester, Ellen, ...

Understanding the pattern of linkage disequilibrium (LD) in the human genome is important both for successful implementation of disease-gene mapping approaches and for inferences about human...

Efficient Multipoint Linkage Analysis through Reduction of Inheritance Space

Markianos, Kyriacos, Daly, Mark J., Kruglyak, Leonid

Computational constraints currently limit exact multipoint linkage analysis to pedigrees of moderate size. We introduce new algorithms that allow analysis of larger pedigrees by reducing the time and...

Exact Multipoint Quantitative-Trait Linkage Analysis in Pedigrees by Variance Components

Pratt, Stephen C., Daly, Mark J., Kruglyak, Leonid

Methods based on variance components are powerful tools for linkage analysis of quantitative traits, because they allow simultaneous consideration of all pedigree members. The central idea is to...

Full-Genome Scan for Linkage in 50 Families Segregating the Bipolar Affective Disease Phenotype

Friddle, Carl, Koskela, Rebecca, Ranade, Koustubh, Hebert, Joan, Cargill, Michele, Clark, Chris D., ...

A genome scan of ∼12-cM initial resolution was done on 50 of a set of 51 carefully ascertained unilineal multiplex families segregating the bipolar affective disorder phenotype. In addition to...

Telomere Length as a Quantitative Trait: Genome-Wide Survey and Genetic Mapping of Telomere Length-Control Genes in Yeast

Gatbonton, Tonibelle, Imbesi, Maria, Nelson, Melisa, Akey, Joshua M, Ruderfer, Douglas M, Kruglyak, Leonid, ...

Telomere length-variation in deletion strains of Saccharomyces cerevisiae was used to identify genes and pathways that regulate telomere length. We found 72 genes that when deleted confer short...

Allele Frequency Matching Between SNPs Reveals an Excess of Linkage Disequilibrium in Genic Regions of the Human Genome

Eberle, Michael A, Rieder, Mark J, Kruglyak, Leonid, Nickerson, Deborah A

Significant interest has emerged in mapping genetic susceptibility for complex traits through whole-genome association studies. These studies rely on the extent of association, i.e., linkage...

Genome-Wide Analysis of Nucleotide-Level Variation in Commonly Used Saccharomyces cerevisiae Strains

Schacherer, Joseph, Ruderfer, Douglas M., Gresham, David, Dolinski, Kara, Botstein, David, Kruglyak, Leonid

Ten years have passed since the genome of Saccharomyces cerevisiae–more precisely, the S288c strain–was completely sequenced. However, experimental work in yeast is commonly performed using...

Identification and Dissection of a Complex DNA Repair Sensitivity Phenotype in Baker's Yeast

Demogines, Ann, Smith, Erin, Kruglyak, Leonid, Alani, Eric

Complex traits typically involve the contribution of multiple gene variants. In this study, we took advantage of a high-density genotyping analysis of the BY (S288c) and RM strains of Saccharomyces...

Breeding Designs for Recombinant Inbred Advanced Intercross Lines

Rockman, Matthew V., Kruglyak, Leonid

Recombinant inbred lines derived from an advanced intercross, in which multiple generations of mating have increased the density of recombination breakpoints, are powerful tools for mapping the loci...

Comparative Developmental Expression Profiling of Two C. elegans Isolates

Capra, Emily J., Skrovanek, Sonja M., Kruglyak, Leonid

Gene expression is known to change during development and to vary among genetically diverse strains. Previous studies of temporal patterns of gene expression during C. elegans development were...

Recombinational Landscape and Population Genomics of Caenorhabditis elegans

Rockman, Matthew V., Kruglyak, Leonid

Recombination rate and linkage disequilibrium, the latter a function of population genomic processes, are the critical parameters for mapping by linkage and association, and their patterns in...

Gene–Environment Interaction in Yeast Gene Expression

Smith, Erin N, Kruglyak, Leonid

The effects of genetic variants on phenotypic traits often depend on environmental and physiological conditions, but such gene–environment interactions are poorly understood. Recently developed...

Using Expression and Genotype to Predict Drug Response in Yeast

Ruderfer, Douglas M., Roberts, David C., Schreiber, Stuart L., Perlstein, Ethan O., Kruglyak, Leonid

Personalized, or genomic, medicine entails tailoring pharmacological therapies according to individual genetic variation at genomic loci encoding proteins in drug-response pathways. It has been...

Protein quantification across hundreds of experimental conditions

Khan, Zia, Bloom, Joshua S., Garcia, Benjamin A., Singh, Mona, Kruglyak, Leonid

Quantitative studies of protein abundance rarely span more than a small number of experimental conditions and replicates. In contrast, quantitative studies of transcript abundance often span hundreds...