1. Genomic characterization of large heterochromatic gaps in the human genome assembly.

    PLoS computational biology 10(5):e1003628 (2014) PMID 24831296 PMCID PMC4022460

    The largest gaps in the human genome assembly correspond to multi-megabase heterochromatic regions composed primarily of two related families of tandem repeats, Human Satellites 2 and 3 (HSat2,3). The abundance of repetitive DNA in these regions challenges standard mapping and assembly algorithm...
  2. Centromere reference models for human chromosomes X and Y satellite arrays.

    Genome Research 24(4):697 (2014) PMID 24501022 PMCID PMC3975068

    The human genome sequence remains incomplete, with multimegabase-sized gaps representing the endogenous centromeres and other heterochromatic regions. Available sequence-based studies within these sites in the genome have demonstrated a role in centromere function and chromosome pairing, necessa...
  3. An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY Challenge.
    Catherine A Brownstein, Alan H Beggs, Nils Homer, Barry Merriman, Timothy W Yu, Katherine C Flannery, Elizabeth T DeChene, Meghan C Towne, Sarah K Savage, Emily N Price, Ingrid A Holm, Lovelace J Luquette, Elaine Lyon, Joseph Majzoub, Peter Neupert, David McCallie, Peter Szolovits, Huntington F Willard, Nancy J Mendelsohn, Renee Temme, Richard S Finkel, Sabrina W Yum, Livija Medne, Shamil R Sunyaev, Ivan Adzhubey, Christopher A Cassa, Paul I W de Bakker, Hatice Duzkale, Piotr Dworzyński, William Fairbrother, Laurent Francioli, Birgit H Funke, Monica A Giovanni, Robert E Handsaker, Kasper Lage, Matthew S Lebo, Monkol Lek, Ignaty Leshchiner, Daniel G MacArthur, Heather McLaughlin, Michael F Murray, Tune H Pers, Paz Polak, Soumya Raychaudhuri, Heidi L Rehm, Rachel Soemedi, Nathan O Stitziel, Sara Vestecka, Jochen Supper, Claudia Gugenmus, Bernward Klocke, Alexander Hahn, Max Schubach, Mortiz Menzel, Saskia Biskup, Peter Freisinger, Mario Deng, Martin Braun, Sven Perner, Richard J H Smith, Janeen L Andorf, Jian Huang, Kelli Ryckman, Val C Sheffield, Edwin M Stone, Thomas Bair, E Ann Black-Ziegelbein, Terry A Braun, Benjamin Darbro, Adam P DeLuca, Diana L Kolbe, Todd E Scheetz, Aiden E Shearer, Rama Sompallae, Kai Wang, Alexander G Bassuk, Erik Edens, Katherine Mathews, Steven A Moore, Oleg A Shchelochkov, Pamela Trapane, Aaron Bossler, Colleen A Campbell, Jonathan W Heusel, Anne Kwitek, Tara Maga, Karin Panzer, Thomas Wassink, Douglas Van Daele, Hela Azaiez, Kevin Booth, Nic Meyer, Michael Segal, Marc S Williams, Gerard Tromp, Peter White, Donald Corsmeier, Sara Fitzgerald-Butt, Gail Herman, Devon Lamb-Thrush, Kim L McBride, David Newsom, Christopher R Pierson, Alexander T Rakowsky, Aleš Maver, Luca Lovrečić, Anja Palandačić, Borut Peterlin, Ali Torkamani, Anna Wedell, Mikael Huss, Andrey Alexeyenko, Jessica M Lindvall, Måns Magnusson, Daniel Nilsson, Henrik Stranneheim, Fulya Taylan, Christian Gilissen, Alexander Hoischen, Bregje van Bon, Helger Yntema, Marcel Nelen, Weidong Zhang, Jason Sager, Lu Zhang, Kathryn Blair, Deniz Kural, Michael Cariaso, Greg Lennon, Asif Javed, Saloni Agrawal, Pauline C Ng, Komal Sandhu, Shuba Krishna, Vamsi Veeramachaneni, Ofer Isakov, Eran Halperin, Eitan Friedman, Noam Shomron, Gustavo Glusman, Jared C Roach, Juan Caballero, Hannah Cox, Denise Mauldin, Seth Ament, Lee Rowen, Daniel Richards, F Anthony San Lucas, Manuel L, Thomas Caskey, Yu Bai, Ying Huang, Fang, Yan Zhang, Zhengyuan Wang, Jorge Barrera, Juan M Garcia-Lobo, Domingo González-Lamuño, Javier Llorca, Maria C Rodriguez, Ignacio Varela, Martin G Reese, Francisco M De La Vega, Edward Kiruluta, Michele Cargill, Reece K Hart, Jon M Sorenson, Gholson J Lyon, David A Stevenson, Bruce E Bray, Barry Moore, Karen Eilbeck, Mark Yandell, Hongyu Zhao, Lin Hou, Xiaowei Chen, Xiting Yan, Mengjie Chen, Cong Li, Can Yang, Murat Gunel, Peining Li, Yong Kong, Austin C Alexander, Zayed I Albertyn, Kym M Boycott, Dennis E Bulman, Paul M K Gordon, A Micheil Innes, Bartha M Knoppers, Jacek Majewski, Christian R Marshall, Jillian S Parboosingh, Sarah L Sawyer, Mark E Samuels, Jeremy Schwartzentruber, Isaac S Kohane, and David Margulies

    Genome Biology 15(3):R53 (2014) PMID 24667040 PMCID PMC4073084

    There is tremendous potential for genome sequencing to improve clinical diagnosis and care once it becomes routinely accessible, but this will require formalizing research methods into clinical best practices in the areas of sequence data generation, analysis, interpretation and reporting. The C...
  4. Public knowledge of and attitudes toward genetics and genetic testing.

    Genetic Testing and Molecular Biomarkers 17(4):327 (2013) PMID 23406207 PMCID PMC3609633

    Variable health literacy and genetic knowledge may pose significant challenges to engaging the general public in personal genomics, specifically with respect to promoting risk comprehension and healthy behaviors. We are conducting a multistage study of individual responses to genomic risk inform...
  5. Sequences associated with centromere competency in the human genome.

    Molecular and Cellular Biology 33(4):763 (2013) PMID 23230266 PMCID PMC3571344

    Centromeres, the sites of spindle attachment during mitosis and meiosis, are located in specific positions in the human genome, normally coincident with diverse subsets of alpha satellite DNA. While there is strong evidence supporting the association of some subfamilies of alpha satellite with c...
  6. Nonrandom X chromosome inactivation is influenced by multiple regions on the murine X chromosome.

    Genetics 192(3):1095 (2012) PMID 22887817 PMCID PMC3522153

    During the development of female mammals, one of the two X chromosomes is inactivated, serving as a dosage-compensation mechanism to equalize the expression of X-linked genes in females and males. While the choice of which X chromosome to inactivate is normally random, X chromosome inactivation ...
  7. Effects of sequence variation on differential allelic transcription factor occupancy and gene expression.

    Genome Research 22(5):860 (2012) PMID 22300769 PMCID PMC3337432

    A complex interplay between transcription factors (TFs) and the genome regulates transcription. However, connecting variation in genome sequence with variation in TF binding and gene expression is challenging due to environmental differences between individuals and cell types. To address this pr...
  8. Uncoupling of genomic and epigenetic signals in the maintenance and inheritance of heterochromatin domains in fission yeast.

    Genetics 190(2):549 (2012) PMID 22143918 PMCID PMC3276613

    Many essential aspects of genome function, including gene expression and chromosome segregation, are mediated throughout development and differentiation by changes in the chromatin state. Along with genomic signals encoded in the DNA, epigenetic processes regulate heritable gene expression patte...
  9. Evidence for sequence biases associated with patterns of histone methylation.

    BMC Genomics 13:367 (2012) PMID 22857523 PMCID PMC3532361

    Combinations of histone variants and modifications, conceptually representing a histone code, have been proposed to play a significant role in gene regulation and developmental processes in complex organisms. While various mechanisms have been implicated in establishing and maintaining epigeneti...
  10. Composition and organization of active centromere sequences in complex genomes.

    BMC Genomics 13:324 (2012) PMID 22817545 PMCID PMC3422206

    Centromeres are sites of chromosomal spindle attachment during mitosis and meiosis. While the sequence basis for centromere identity remains a subject of considerable debate, one approach is to examine the genomic organization at these active sites that are correlated with epigenetic marks of ce...
  11. Competencies: a cure for pre-med curriculum.

    Science 334(6057):760 (2011) PMID 22076362

  12. Allele-specific distribution of RNA polymerase II on female X chromosomes.

    Human Molecular Genetics 20(20):3964 (2011) PMID 21791549 PMCID PMC3177651

    While the distribution of RNA polymerase II (PolII) in a variety of complex genomes is correlated with gene expression, the presence of PolII at a gene does not necessarily indicate active expression. Various patterns of PolII binding have been described genome wide; however, whether or not PolI...
  13. Analysis of DNA methylation in a three-generation family reveals widespread genetic influence on epigenetic regulation.

    PLoS Genetics 7(8):e1002228 (2011) PMID 21852959 PMCID PMC3154961

    The methylation of cytosines in CpG dinucleotides is essential for cellular differentiation and the progression of many cancers, and it plays an important role in gametic imprinting. To assess variation and inheritance of genome-wide patterns of DNA methylation simultaneously in humans, we appli...
  14. Comparative analysis of the primate X-inactivation center region and reconstruction of the ancestral primate XIST locus.

    Genome Research 21(6):850 (2011) PMID 21518738 PMCID PMC3106318

    Here we provide a detailed comparative analysis across the candidate X-Inactivation Center (XIC) region and the XIST locus in the genomes of six primates and three mammalian outgroup species. Since lemurs and other strepsirrhine primates represent the sister lineage to all other primates, this a...
  15. Organization and molecular evolution of CENP-A--associated satellite DNA families in a basal primate genome.

    Genome Biology and Evolution 3:1136 (2011) PMID 21828373 PMCID PMC3194837

    Centromeric regions in many complex eukaryotic species contain highly repetitive satellite DNAs. Despite the diversity of centromeric DNA sequences among species, the functional centromeres in all species studied to date are marked by CENP-A, a centromere-specific histone H3 variant. Although it...
  16. Considerations for the impact of personal genome information: a study of genomic profiling among genetics and genomics professionals.

    Journal of Genetic Counseling 19(4):387 (2010) PMID 20352309

    With the expansion of genomic-based clinical applications, it is important to consider the potential impact of this information particularly in terms of how it may be interpreted and applied to personal perceptions of health. As an initial step to exploring this question, we conducted a study to...
  17. Heritable individual-specific and allele-specific chromatin signatures in humans.

    Science 328(5975):235 (2010) PMID 20299549 PMCID PMC2929018

    The extent to which variation in chromatin structure and transcription factor binding may influence gene expression, and thus underlie or contribute to variation in phenotype, is unknown. To address this question, we cataloged both individual-to-individual variation and differences between homol...
  18. Genomic and personalized medicine: foundations and applications.

    Translational Research 154(6):277 (2009) PMID 19931193

    The last decade has witnessed a steady embrace of genomic and personalized medicine by senior government officials, industry leadership, health care providers, and the public. Genomic medicine, which is the use of information from genomes and their derivatives (RNA, proteins, and metabolites) to...
  19. The impact of local genome sequence on defining heterochromatin domains.

    PLoS Genetics 5(4):e1000453 (2009) PMID 19360117 PMCID PMC2659443

    Characterizing how genomic sequence interacts with trans-acting regulatory factors to implement a program of gene expression in eukaryotic organisms is critical to understanding genome function. One means by which patterns of gene expression are achieved is through the differential packaging of ...
  20. A national clinical decision support infrastructure to enable the widespread and consistent practice of genomic and personalized medicine.

    BMC Medical Informatics and Decision Making 9:17 (2009) PMID 19309514 PMCID PMC2666673

    In recent years, the completion of the Human Genome Project and other rapid advances in genomics have led to increasing anticipation of an era of genomic and personalized medicine, in which an individual's health is optimized through the use of all available patient data, including data on the i...