Genomic characterization of large heterochromatic gaps in the human genome assembly.
PLoS computational biology 10(5):e1003628 (2014)
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...
Centromere reference models for human chromosomes X and Y satellite arrays.
Genome Research 24(4):697 (2014)
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...
An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY Challenge.
Genome Biology 15(3):R53 (2014)
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...
Public knowledge of and attitudes toward genetics and genetic testing.
Genetic Testing and Molecular Biomarkers 17(4):327 (2013)
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...
Sequences associated with centromere competency in the human genome.
Molecular and Cellular Biology 33(4):763 (2013)
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...
Nonrandom X chromosome inactivation is influenced by multiple regions on the murine X chromosome.
Genetics 192(3):1095 (2012)
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 ...
Effects of sequence variation on differential allelic transcription factor occupancy and gene expression.
Genome Research 22(5):860 (2012)
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...
Uncoupling of genomic and epigenetic signals in the maintenance and inheritance of heterochromatin domains in fission yeast.
Genetics 190(2):549 (2012)
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...
Evidence for sequence biases associated with patterns of histone methylation.
BMC Genomics 13:367 (2012)
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...
Composition and organization of active centromere sequences in complex genomes.
BMC Genomics 13:324 (2012)
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...
Competencies: a cure for pre-med curriculum.
Science 334(6057):760 (2011)
Allele-specific distribution of RNA polymerase II on female X chromosomes.
Human Molecular Genetics 20(20):3964 (2011)
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...
Analysis of DNA methylation in a three-generation family reveals widespread genetic influence on epigenetic regulation.
PLoS Genetics 7(8):e1002228 (2011)
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...
Comparative analysis of the primate X-inactivation center region and reconstruction of the ancestral primate XIST locus.
Genome Research 21(6):850 (2011)
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...
Organization and molecular evolution of CENP-A--associated satellite DNA families in a basal primate genome.
Genome Biology and Evolution 3:1136 (2011)
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...
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)
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...
Heritable individual-specific and allele-specific chromatin signatures in humans.
Science 328(5975):235 (2010)
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...
Genomic and personalized medicine: foundations and applications.
Translational Research 154(6):277 (2009)
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...
The impact of local genome sequence on defining heterochromatin domains.
PLoS Genetics 5(4):e1000453 (2009)
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 ...
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)
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...