Len A. Pennacchio

The INSIG2rs7566605 genetic variant does not play a major role in obesity in a sample of 24,722 individuals from four cohorts (2009)

Bressler, Jan, Fornage, Myriam, Hanis, Craig L, Kao, Wen, Lewis, Cora E, McPherson, Ruth, ...

Abstract Background In a genome-wide association study performed in the Framingham Offspring Cohort, individuals homozygous for the rs7566605 C allele located upstream of insulin-induced gene 2 (...

Response to comment on "Human-specific gain of function in a developmental enhancer" (2009)

Prabhakar, Shyam, Visel, Axel, Akiyama, Jennifer A., Shoukry, Malak, Lewis, Keith D., Holt, Amy, ...

Duret and Galtier argue that human-specific sequence divergence and gain of function in the HACNS1 enhancer result from deleterious biased gene conversion (BGC) with no contribution from positive...

Response to comment on "Human-specific gain of function in a developmental enhancer" (2009)

Prabhakar, Shyam, Visel, Axel, Akiyama, Jennifer A., Shoukry, Malak, Lewis, Keith D., Holt, Amy, ...

Duret and Galtier argue that human-specific sequence divergence and gain of function in the HACNS1 enhancer result from deleterious biased gene conversion (BGC) with no contribution from positive...

Association of functionally significant Melanocortin-4 but not Melanocortin-3 receptor mutations with severe adult obesity in a large North American case-control study (2009)

Calton, Melissa A., Ersoy, Baran A., Zhang, Sumei, Kane, John P., Malloy, Mary J., Pullinger, Clive R., ...

Functionally significant heterozygous mutations in the Melanocortin-4 receptor (MC4R) have been implicated in 2.5% of early onset obesity cases in European cohorts. The role of mutations in this gene...

Medical Sequencing at the Extremes of Human Body Mass REPORT (2008)

Nadav Ahituv, Nihan Kavaslar, Wendy Schackwitz, Anna Ustaszewska, Joel Martin, Sybil Hébert, ...

Body weight is a quantitative trait with significant heritability in humans. To identify potential genetic contributors to this phenotype, we resequenced the coding exons and splice junctions of 58...

Human-specific gain of function in a developmental enhancer (2008)

Prabhakar, Shyam, Visel, Axel, Akiyama, Jennifer A., Shoukry, Malak, Lewis, Keith D., Holt, Amy, ...

Changes in gene regulation are thought to have contributed to the evolution of human development. However, in vivo evidence for uniquely human developmental regulatory function has remained elusive....

The amphioxus genome and the evolution of the chordate karyotype (2008)

Putnam, Nicholas H., Butts, Thomas, Ferrier, David E. K., Furlong, Rebecca F., Hellsten, Uffe, Kawashima, Takeshi, ...

Lancelets ('amphioxus') are the modern survivors of an ancient chordate lineage, with a fossil record dating back to the Cambrian period. Here we describe the structure and gene content of the highly...

Human cathepsin L rescues the neurodegeneration and lethality in cathepsin B/L double deficient mice (2008)

Sevenich, Lisa, Pennacchio, Len A., Peters, Christoph, Reinheckel, Thomas

Cathepsin B (CTSB) and cathepsin L (CTSL) are two widely expressed cysteine proteases thought to predominantly reside within lysosomes. Functional analysis of CTSL in humans is complicated by the...

* Corresponding authors Summary (2008)

Nameeta Shah, Olivier Couronne, Len A. Pennacchio, Michael Brudno, Serafim Batzoglou, Wes Bethel, ...

The power of multi-sequence comparison for biological discovery is well established. The need for new capabilities to visualize and compare cross-species alignment data is intensified by the growing...

§ To whom correspondence should be addressed (2008)

Nameeta Shah, Michael V. Teplitsky, Simon Minovitsky, Len A. Pennacchio, Philip Hugenholtz, Bernd Hamann, ...

Background Recent advances in sequencing technologies promise to provide a better understanding of the genetics of human disease as well as the evolution of microbial populations. Single Nucleotide...

Integrated analysis of homozygous deletions, focal amplifications, and sequence alterations in breast and colorectal cancers. (2008)

Leary, Rebecca J., Lin, Jimmy C., Cummins, Jordan, Boca, Simina, Wood, Laura D., Parsons, D. Williams, ...

We have performed a genome-wide analysis of copy number changes in breast and colorectal tumors using approaches that can reliably detect homozygous deletions and amplifications. We found that the...

Association of common variants in the Joubert syndrome gene (AHI1) with autism (2008)

Alvarez Retuerto, Ana I., Cantor, Rita M., Gleeson, Joseph G., Ustaszewska, Anna, Schackwitz, Wendy S., Pennacchio, Len A., ...

It has been suggested that autism, like other complex genetic disorders, may benefit from the study of rare or Mendelian variants associated with syndromic or non-syndromic forms of the disease....

The amphioxus genome illuminates vertebrate origins and cephalochordate biology (2008)

Holland, Linda Z., Albalat, Ricard, Azumi, Kaoru, Benito-Gutiérrez, Èlia, Blow, Matthew J., Bronner-Fraser, Marianne, ...

Cephalochordates, urochordates, and vertebrates evolved from a common ancestor over 520 million years ago. To improve our understanding of chordate evolution and the origin of vertebrates, we...

Deletion of Ultraconserved Elements Yields Viable Mice (2007)

Nadav Ahituv, Yiwen Zhu, Axel Visel, Amy Holt, Veena Afzal, Len A. Pennacchio, ...

Ultraconserved elements have been suggested to retain extended perfect sequence identity between the human, mouse, and rat genomes due to essential functional properties. To investigate the...

Deletion of ultraconserved elements yields viable mice (2007)

Ahituv, Nadav, Zhu, Yiwen, Visel, Axel, Holt, Amy, Afzal, Veena, Pennacchio, Len A., ...

Ultraconserved elements have been suggested to retain extended perfect sequence identity between the human, mouse, and rat genomes due to essential functional properties. To investigate the...

VISTA Enhancer Browser--a database of tissue-specific human enhancers (2007)

Visel, Axel, Minovitsky, Simon, Dubchak, Inna, Pennacchio, Len A.

Despite the known existence of distant-acting cis-regulatory elements in the human genome, only a small fraction of these elements has been identified and experimentally characterized in vivo. This...

Predicting tissue-specific enhancers in the human genome (2007)

Pennacchio, Len A., Loots, Gabriela G., Nobrega, Marcelo A., Ovcharenko, Ivan

Determining how transcriptional regulatory signals are encoded in vertebrate genomes is essential for understanding the origins of multicellular complexity; yet the genetic code of vertebrate gene...

Most of rare missense alleles in humans are deleterious: implications for evolution of complex disease and association studies (2006)

Kryukov, Gregory V., Pennacchio, Len A., Sunyaev, Shamil R.

The accumulation of mildly deleterious missense mutations in individual human genomes has been proposed to be a genetic basis for complex diseases. The plausibility of this hypothesis depends on...

Enhancer Identification through Comparative Genomics (2006)

Visel, Axel, Bristow, James, Pennacchio, Len A.

With the availability of genomic sequence from numerous vertebrates, a paradigm shift has occurred in the identification of distant-acting gene regulatory elements. In contrast to traditional...

Gain-of-function SOS1 mutations cause a distinctive form of noonan syndrome (2006)

Tartaglia, Marco, Pennacchio, Len A., Zhao, Chen, Yadav, Kamlesh K., Fodale, Valentina, Sarkozy, Anna, ...

Noonan syndrome (NS) is a developmental disorder characterized by short stature, facial dysmorphia, congenital heart defects and skeletal anomalies1. Increased RAS-mitogenactivated protein kinase...

Medical Sequencing at the extremes of Human Body Mass (2006)

Ahituv, Nadav, Kavaslar, Nihan, Schackwitz, Wendy, Ustaszewski, Anna, Martin, Joes, Hebert, Sybil, ...

Body weight is a quantitative trait with significant heritability in humans. To identify potential genetic contributors to this phenotype, we resequenced the coding exons and splice junctions of 58...

VISTA Enhancer Browser--A Database of Tissue-Specific Human Enhancers (2006)

Visel, Axel, Minovitsky, Simon, Dubchak, Inna, Pennacchio, Len A.

Despite the known existence of distant-acting cis-regulatory elements in the human genome, only a small fraction of these elements has been identified and experimentally characterized in vivo. This...

Predicting Tissue-Specific Enhancers in the Human Genome (2006)

Pennacchio, Len A., Loots, Gabriela G., Nobrega, Marcelo A., Ovcharenko, Ivan

Determining how transcriptional regulatory signals are encoded in vertebrate genomes is essential for understanding the origins of multi-cellular complexity; yet the genetic code of vertebrate gene...

In Vivo Enhancer Analysis Chromosome 16 Conserved Noncoding Sequences (2006)

Pennacchio, Len A., Ahituv, Nadav, Moses, Alan M., Nobrega, Marcelo, Prabhakar, Shyam, Shoukry, Malak, ...

The identification of enhancers with predicted specificities in vertebrate genomes remains a significant challenge that is hampered by a lack of experimentally validated training sets. In this study,...

Close sequence comparisons are sufficient to identify human cis-regulatory elements (2006)

Prabhakar, Shyam, Poulin, Francis, Shoukry, Malak, Afzal, Veena, Rubin, Edward M., Couronne, Olivier, ...

Cross-species DNA sequence comparison is the primary method used to identify functional noncoding elements in human and other large genomes. However, little is known about the relative merits of...

A PYY Q62P variant linked to human obesity (2006)

Ahituv, Nadav, Kavaslar, Nihan, Schackwitz, Wendy, Ustaszewska, Anna, Collier, John Michael, Hébert, Sybil, ...

Peptide YY (PYY) has been implicated in the control of food intake through functional studies in rodents and humans. To investigate whether genetic alterations within this gene result in abnormal...

Close sequence comparisons are sufficient to identify human cis-regulatory elements (2006)

Prabhakar, Shyam, Poulin, Francis, Shoukry, Malak, Afzal, Veena, Rubin, Edward M., Couronne, Olivier, ...

Cross-species DNA sequence comparison is the primary method used to identify functional noncoding elements in human and other large genomes. However, little is known about the relative merits of...

SNP-VISTA: An interactive SNP visualization tool (2005)

Shah, Nameeta, Teplitsky, Michael V, Minovitsky, Simon, Pennacchio, Len A, Hugenholtz, Philip, Hamann, Bernd, ...

Abstract Background Recent advances in sequencing technologies promise to provide a better understanding of the genetics of human disease as well as the evolution of microbial populations. Single...

SNP-VISTA: An interactive SNP visualization tool (2005)

Shah, Nameeta, Teplitsky, Michael V, Minovitsky, Simon, Pennacchio, Len A, Hugenholtz, Philip, Hamann, Bernd, ...

Background: Recent advances in sequencing technologies promise to provide a better understanding of the genetics of human disease as well as the evolution of microbial populations. Single Nucleotide...

Close Sequence Comparisons are Sufficient to Identify Human cis-Regulatory Elements (2005)

Prabhakar, Shyam, Poulin, Francis, Shoukry, Malak, Afzal, Veena, Rubin, Edward M., Couronne, Olivier, ...

Cross-species DNA sequence comparison is the primary method used to identify functional noncoding elements in human and other large genomes. However, little is known about the relative merits of...

Lack of Support for the Association between GAD2 Polymorphisms and Severe Human Obesity (2005)

Michael M. Swarbrick, Björn Waldenmaier, Len A. Pennacchio, Denise L. Lind, Martha M. Cavazos, Frank Geller, ...

A large genetic study involving multiple populations is not able to replicate previous findings linking variation in the GAD2 gene to susceptibility to obesity.

Lack of Support for the Association between GAD2 Polymorphisms and Severe Human Obesity (2005)

Michael M. Swarbrick, Björn Waldenmaier, Len A. Pennacchio, Denise L. Lind, Martha M. Cavazos, Frank Geller, ...

The demonstration of association between common genetic variants and chronic human diseases such as obesity could have profound implications for the prediction, prevention, and treatment of these...

SNP-VISTA: An Interactive SNPs Visualization Tool (2005)

Shah, Nameeta, Teplitsky, Michael V., Pennacchio, Len A., Hugenholtz, Philip, Hamann, Bernd, Dubchak, Inna L.

Recent advances in sequencing technologies promise better diagnostics for many diseases as well as better understanding of evolution of microbial populations. Single Nucleotide Polymorphisms (SNPs)...

A PYY Q62P variant linked to human obesity (2005)

Ahituv, Nadav, Kavaslar, Nihan, Schackwitz, Wendy, Ustaszewska, Anna, Collier, John Michael, Hebert, Sybil, ...

Members of the pancreatic polypeptide family and their receptors have been implicated in the control of food intake in rodents and humans. To investigate whether nucleotide changes in these candidate...

Lack of MEF2A mutations in coronary artery disease (2004)

Weng, Li, Kavaslar, Nihan, Ustaszewska, Anna, Doelle, Heather, Schackwitz, Wendy, Hebert, Sybil, ...

Mutations in MEF2A have been implicated in an autosomal dominant form of coronary artery disease (adCAD1). In this study we sought to determine whether severe mutations in MEF2A might also explain...

Lack of Support for the Association Between GAD2 Polymorphisms and Severe Human Obesity (2004)

Swarbrick, Michael M., Waldenmaier, Bjorn, Pennacchio, Len A., Lind, Denise L., Cavazos, Martha M., Geller, Frank, ...

Demonstration of association between common genetic variants and chronic human diseases such as obesity could have profound implications for the prediction, prevention and treatment of these...

Comparative genomic analysis reveals a distant liver enhancer upstream of the COUP-TFII gene (2004)

Baroukh, Nadine, Ahituv, Nadav, Chang, Jessie, Shoukry, Malak, Afzal, Veena, Rubin, Edward M., ...

COUP-TFII is a central nuclear hormone receptor that tightly regulates the expression of numerous target lipid metabolism genes in vertebrates. However, it remains unclear how COUP-TFII itself is...

The sequence and analysis of duplication rich human chromosome 16 (2004)

Martin, Joel, Han, Cliff, Gordon, Laurie A., Terry, Astrid, Prabhakar, Shyam, She, Xinwei, ...

We report here the 78,884,754 base pairs of finished human chromosome 16 sequence, representing over 99.9 percent of its euchromatin. Manual annotation revealed 880 protein coding genes confirmed by...

The complete sequence of human chromosome 5 (2004)

Schmutz, Jeremy, Martin, Joel, Terry, Astrid, Couronne, Olivier, Grimwood, Jane, Lowry, State, ...

Chromosome 5 is one of the largest human chromosomes yet has one of the lowest gene densities. This is partially explained by numerous gene-poor regions that display a remarkable degree of noncoding...

Phylo-VISTA: An Interactive Visualization Tool for Multiple DNA Sequence Alignments (2004)

Shah, Nameeta, Couronne, Olivier, Pennacchio, Len A., Brudno, Michael, Batzoglou, Serafim, Bethel, E. Wes, ...

We have developed Phylo-VISTA (Shah et al., 2003), an interactive software tool for analyzing multiple alignments by visualizing a similarity measure for DNA sequences of multiple species. The...

Apolipoprotein A5 is an inflammatory responsive gene down-regulated by tumor necrosis factor alpha and interleukin-1 (2004)

Genoux, Annelise, Gervois, Philippe, Rommens, Corinne, Dehondt, Helene, Foulard, Michel, Dehennault, Maud, ...

Several epidemiological studies have established that elevated plasma triglyceride concentrations constitute an independent risk factor for cardiovascular diseases. In addition, systemic inflammation...

Phosphorylation-dependent down-regulation of apolipoprotein A5 by insulin (2004)

Nowak, Maxine, Helleboid-Chapman, Audrey, Jakel, Heidelinde, Rommens, Corinne, Martin, Genevieve, Duran-Sandoval, Daniel, ...

The apolipoprotein A5 (APOA5) gene has been shown to be important in lowering plasma triglyceride levels. Since several studies have shown that hyperinsulinemia is associated with...

Cathepsin L is required for endothelial progenitor cell-induced neovascularization (2004)

Urbich, Carmen, Heeschen, Christopher, Aicher, Alexandra, Sasaki, Ken-ichiro, Bruhl, Thomas, Hofmann, Wolf K., ...

Infusion of endothelial progenitor cells (EPCs), but not of mature endothelial cells (ECs), promotes neovascularization after ischemia. We performed a gene expression profiling of EPCs and ECs to...

Mechanism of lipid lowering in mice expressing human apolipoprotein A5 (2004)

Fruchart-Najib, Jamila, Bauge, Eric, Niculescu, Loredan-Stefan, Pham, Tatiana, Thomas, Benoit, Rommens, Corinne, ...

Recently, we reported that apoAV plays key role in triglycerides lowering. Here, we attempted to determine the mechanism underlying this hypotriglyceridemic effect. We showed that triglyceride...

Phylo-VISTA: Interactive Visualization of Multiple DNA Sequence Alignments (2004)

Nameeta Shah Olivier, Olivier Couronne, Len A. Pennacchio, Michael Brudno, Serafim Batzoglou, Wes Bethel, ...

an Internet browser with Java Plug-in 1.4.2 and it is integrated into the global alignment program LAGAN at http://lagan.stanford.edu. Contact phylovista@lbl.gov 1 Introduction Large-scale genome...

Haplotypes in the APOA1-C3-A4-A5 Gene Cluster affect Plasma Lipids in both Humans and Baboons (2004)

Wang, Qian-fei, Liu, Xin, O'Connell, Jeff, Peng, Ze, Krauss, Ronald M., Rainwater, David L., ...

Genetic studies in non-human primates serve as a potential strategy for identifying genomic intervals where polymorphisms impact upon human disease-related phenotypes. It remains unclear, however,...

Phylo-VISTA: interactive visualization of multiple DNA sequence alignments (2004)

Shah, Nameeta, Couronne, Olivier, Pennacchio, Len A., Brudno, Michael, Batzoglou, Serafim, Wes Bethel, E., ...

Motivation The power of multi-sequence comparison for biological discovery is well established. The need for new capabilities to visualize and compare cross-species alignment data is intensified by...

Haplotypes in the APOA1-C3-A4-A5 gene cluster affect plasma lipids in both humans and baboons (2004)

Wang, Qian-fei, Liu, Xin, O'Connell, Jeff, Peng, Ze, Krauss, Ronald M., Rainwater, David L., ...

Genetic studies in non-human primates serve as a potential strategy for identifying genomic intervals where polymorphisms impact upon human disease-related phenotypes. It remains unclear, however,...

Phylo-VISTA: interactive visualization of multiple DNA sequence alignments (2004)

Shah, Nameeta, Couronne, Olivier, Pennacchio, Len A., Brudno, Michael, Batzoglou, Serafim, Bethel, E. Wes, ...

Motivation: The power of multi-sequence comparison for biological discovery is well established. The need for new capabilities to visualize and compare cross-species alignment data is intensified by...

Haplotypes in the APOA1-C3-A4-A5 Gene Cluster affect Plasma Lipids in both Humans and Baboons (2004)

Wang, Qian-fei, Liu, Xin, O'Connell, Jeff, Peng, Ze, Krauss, Ronald M., Rainwater, David L., ...

Genetic studies in non-human primates serve as a potential strategy for identifying genomic intervals where polymorphisms impact upon human disease-related phenotypes. It remains unclear, however,...

Phylo-VISTA: interactive visualization of multiple DNA sequence alignments (2004)

Shah, Nameeta, Couronne, Olivier, Pennacchio, Len A., Brudno, Michael, Batzoglou, Serafim, Wes Bethel, E., ...

Motivation The power of multi-sequence comparison for biological discovery is well established. The need for new capabilities to visualize and compare cross-species alignment data is intensified by...

Haplotypes in the APOA1-C3-A4-A5 gene cluster affect plasma lipids in both humans and baboons (2003)

Wang, Qian-fei, Liu, Xin, O'Connell, Jeff, Peng, Ze, Krauss, Ronald M., Rainwater, David L., ...

Genetic studies in non-human primates serve as a potential strategy for identifying genomic intervals where polymorphisms impact upon human disease-related phenotypes. It remains unclear, however,...

Independent effects of apolipoprotein AV and apolipoprotein CIII on plasma triglyceride concentrations (2003)

Baroukh, Nadine N., Bauge, Eric, Akiyama, Jennifer, Chang, Jessie, Fruchart, Jean-Charles, Rubin, Edward M., ...

Both the apolipoprotein A5 and C3 genes have repeatedly been shown to play an important role in determining plasma triglyceride concentrations in humans and mice. In mice, transgenic and knockout...

Phylo-VISTA: An interactive visualization tool for multiple DNA sequence alignments (2003)

Shah, Nameeta, Couronne, Olivier, Pennacchio, Len A., Brudno, Michael, Batzoglou, Serafim, Bethel, E. Wes, ...

Motivation. The power of multi-sequence comparison for biological discovery is well established and sequence data from a growing list of organisms is becoming available. Thus, a need exists for...

Phylo-VISTA: An Interactive Visualization Tool for Multiple DNA Sequence Alignments (2003)

Nameeta Shah, Olivier Couronne, Len A. Pennacchio, Michael Brudno, Serafim Batzoglou, E. Wes Bethel, ...

We have developed Phylo-VISTA (Shah et al., 2003) , an interactive software tool for analyzing multiple alignments by visualizing a similarity measure for DNA sequences of multiple species. The...

Linkage and association of haplotypes at the APOA1/C3/A4/A5 gene cluster to familial combined hyperlipidemia (2002)

Eichenbaum-Voline, Sophie, Olivier, Michael, Jones, Emma L., Naoumova, Rossitza P., Jones, Bethan, Gau, Brian, ...

Combined hyperlipidemia (CHL) is a common disorder of lipid metabolism that leads to an increased risk of cardiovascular disease. The lipid profile of CHL is characterised by high levels of...

Apolipoprotein A5: A newly identified gene impacting plasma triglyceride levels in humans and mice (2002)

Pennacchio, Len A., Rubin, Edward M.

Apolipoprotein A5 (APOA5) is a newly described member of the apolipoprotein gene family whose initial discovery arose from comparative sequence analysis of the mammalian APOA1/C3/A4 gene cluster....

Two independent apolipoprotein A5 haplotypes influence human plasma triglyceride levels (2002)

Pennacchio, Len A., Olivier, Michael, Hubacek, Jaroslav A., Krauss, Ronald M., Rubin, Edward M., Cohen, Jonathan C.

The recently identified apolipoprotein A5 gene (APOA5) has been shown to play an important role in determining plasma triglyceride concentrations in humans and mice. We previously identified an APOA5...

Relative contribution of variation within the APOC3/A4/A5 gene cluster in determining plasma triglycerides (2002)

Talmud, Philippa J., Hawe, Emma, Martin, Steve, Olivier, Michael, Miller, George J., Rubin, Edward M., ...

Since triglycerides (TG) are a major independent risk factor for coronary heart disease, understanding their genetic and environmental determinants is of major importance. Mouse models indicate an...

Cystatin B-deficient mice have increased expression of apoptosis and glial activation genes (2001)

Lieuallen, Kimberly, Pennacchio, Len A., Park, Morgan, Myers, Richard M., Lennon, Gregory G.

Loss-of-function mutations in the cystatin B (Cstb) gene cause a neurological disorder known as Unverricht–Lundborg disease (EPM1) in human patients. Mice that lack Cstb provide a mammalian model...

Insulin-Mediated Down-Regulation of Apolipoprotein A5 Gene Expression through the Phosphatidylinositol 3-Kinase Pathway: Role of Upstream Stimulatory Factor

Nowak, Maxime, Helleboid-Chapman, Audrey, Jakel, Heidelinde, Martin, Geneviève, Duran-Sandoval, Daniel, Staels, Bart, ...

The apolipoprotein A5 gene (APOA5) has been repeatedly implicated in lowering plasma triglyceride levels. Since several studies have demonstrated that hyperinsulinemia is associated with...

Lack of MEF2A mutations in coronary artery disease

Weng, Li, Kavaslar, Nihan, Ustaszewska, Anna, Doelle, Heather, Schackwitz, Wendy, Hébert, Sybil, ...

Mutations in MEF2A have been implicated in an autosomal dominant form of coronary artery disease (adCAD1). In this study we sought to determine whether severe mutations in MEF2A might also explain...

Lack of Support for the Association between GAD2 Polymorphisms and Severe Human Obesity

Swarbrick, Michael M, Waldenmaier, Björn, Pennacchio, Len A, Lind, Denise L, Cavazos, Martha M, Geller, Frank, ...

The demonstration of association between common genetic variants and chronic human diseases such as obesity could have profound implications for the prediction, prevention, and treatment of these...

Apoa5 Q139X truncation predisposes to late-onset hyperchylomicronemia due to lipoprotein lipase impairment

Marçais, Christophe, Verges, Bruno, Charrière, Sybil, Pruneta, Valérie, Merlin, Micheline, Billon, Stéphane, ...

While type 1 hyperlipidemia is associated with lipoprotein lipase or apoCII deficiencies, the etiology of type 5 hyperlipidemia remains largely unknown. We explored a new candidate gene, APOA5, for...

Comparative genomic analysis as a tool for biological discovery

Nobrega, Marcelo A, Pennacchio, Len A

The recent completion of the human genome sequence has enabled the identification of a large fraction of our gene catalogue and their physical chromosomal position. However, current efforts lag at...

Insulin-Mediated Down-Regulation of Apolipoprotein A5 Gene Expression through the Phosphatidylinositol 3-Kinase Pathway: Role of Upstream Stimulatory Factor

Nowak, Maxime, Helleboid-Chapman, Audrey, Jakel, Heidelinde, Martin, Geneviève, Duran-Sandoval, Daniel, Staels, Bart, ...

The apolipoprotein A5 gene (APOA5) has been repeatedly implicated in lowering plasma triglyceride levels. Since several studies have demonstrated that hyperinsulinemia is associated with...

Lack of MEF2A mutations in coronary artery disease

Weng, Li, Kavaslar, Nihan, Ustaszewska, Anna, Doelle, Heather, Schackwitz, Wendy, Hébert, Sybil, ...

Mutations in MEF2A have been implicated in an autosomal dominant form of coronary artery disease (adCAD1). In this study we sought to determine whether severe mutations in MEF2A might also explain...

Lack of Support for the Association between GAD2 Polymorphisms and Severe Human Obesity

Swarbrick, Michael M, Waldenmaier, Björn, Pennacchio, Len A, Lind, Denise L, Cavazos, Martha M, Geller, Frank, ...

The demonstration of association between common genetic variants and chronic human diseases such as obesity could have profound implications for the prediction, prevention, and treatment of these...

Apoa5 Q139X truncation predisposes to late-onset hyperchylomicronemia due to lipoprotein lipase impairment

Marçais, Christophe, Verges, Bruno, Charrière, Sybil, Pruneta, Valérie, Merlin, Micheline, Billon, Stéphane, ...

While type 1 hyperlipidemia is associated with lipoprotein lipase or apoCII deficiencies, the etiology of type 5 hyperlipidemia remains largely unknown. We explored a new candidate gene, APOA5, for...

Comparative genomic analysis as a tool for biological discovery

Nobrega, Marcelo A, Pennacchio, Len A

The recent completion of the human genome sequence has enabled the identification of a large fraction of our gene catalogue and their physical chromosomal position. However, current efforts lag at...

Close sequence comparisons are sufficient to identify human cis-regulatory elements

Prabhakar, Shyam, Poulin, Francis, Shoukry, Malak, Afzal, Veena, Rubin, Edward M., Couronne, Olivier, ...

Cross-species DNA sequence comparison is the primary method used to identify functional noncoding elements in human and other large genomes. However, little is known about the relative merits of...

VISTA Enhancer Browser—a database of tissue-specific human enhancers

Visel, Axel, Minovitsky, Simon, Dubchak, Inna, Pennacchio, Len A.

Despite the known existence of distant-acting cis-regulatory elements in the human genome, only a small fraction of these elements has been identified and experimentally characterized in vivo. This...

Predicting tissue-specific enhancers in the human genome

Pennacchio, Len A., Loots, Gabriela G., Nobrega, Marcelo A., Ovcharenko, Ivan

Determining how transcriptional regulatory signals are encoded in vertebrate genomes is essential for understanding the origins of multicellular complexity; yet the genetic code of vertebrate gene...

Deletion of Ultraconserved Elements Yields Viable Mice

Ahituv, Nadav, Zhu, Yiwen, Visel, Axel, Holt, Amy, Afzal, Veena, Pennacchio, Len A, ...

Ultraconserved elements have been suggested to retain extended perfect sequence identity between the human, mouse, and rat genomes due to essential functional properties. To investigate the...

Medical Sequencing at the Extremes of Human Body Mass

Ahituv, Nadav, Kavaslar, Nihan, Schackwitz, Wendy, Ustaszewska, Anna, Martin, Joel, Hébert, Sybil, ...

Body weight is a quantitative trait with significant heritability in humans. To identify potential genetic contributors to this phenotype, we resequenced the coding exons and splice junctions of 58...

Most Rare Missense Alleles Are Deleterious in Humans: Implications for Complex Disease and Association Studies

Kryukov, Gregory V., Pennacchio, Len A., Sunyaev, Shamil R.

The accumulation of mildly deleterious missense mutations in individual human genomes has been proposed to be a genetic basis for complex diseases. The plausibility of this hypothesis depends on...

The amphioxus genome illuminates vertebrate origins and cephalochordate biology

Holland, Linda Z., Albalat, Ricard, Azumi, Kaoru, Benito-Gutiérrez, Èlia, Blow, Matthew J., Bronner-Fraser, Marianne, ...

Cephalochordates, urochordates, and vertebrates evolved from a common ancestor over 520 million years ago. To improve our understanding of chordate evolution and the origin of vertebrates, we...

Rare loss-of-function mutations in ANGPTL family members contribute to plasma triglyceride levels in humans

Romeo, Stefano, Yin, Wu, Kozlitina, Julia, Pennacchio, Len A., Boerwinkle, Eric, Hobbs, Helen H., ...

The relative activity of lipoprotein lipase (LPL) in different tissues controls the partitioning of lipoprotein-derived fatty acids between sites of fat storage (adipose tissue) and oxidation (heart...

Integrated analysis of homozygous deletions, focal amplifications, and sequence alterations in breast and colorectal cancers

Leary, Rebecca J., Lin, Jimmy C., Cummins, Jordan, Boca, Simina, Wood, Laura D., Parsons, D. Williams, ...

We have performed a genome-wide analysis of copy number changes in breast and colorectal tumors using approaches that can reliably detect homozygous deletions and amplifications. We found that the...

Contrasting Patterns of Sequence Evolution at the Functionally Redundant bric à brac Paralogs in Drosophila melanogaster

Bickel, Ryan D., Schackwitz, Wendy S., Pennacchio, Len A., Nuzhdin, Sergey V., Kopp, Artyom

Genes with overlapping expression and function may gradually diverge despite retaining some common functions. To test whether such genes show distinct patterns of molecular evolution within species,...

Massively parallel sequencing identifies the gene Megf8 with ENU-induced mutation causing heterotaxy

Zhang, Zhen, Alpert, Deanne, Francis, Richard, Chatterjee, Bishwanath, Yu, Qing, Tansey, Terry, ...

Forward genetic screens with ENU (N-ethyl-N-nitrosourea) mutagenesis can facilitate gene discovery, but mutation identification is often difficult. We present the first study in which an ENU- induced...