Leslie G Biesecker

Summary

Affiliation: National Institutes of Health
Country: USA

Publications

  1. pmc Identification of candidate genes involved in coronary artery calcification by transcriptome sequencing of cell lines
    Shurjo K Sen
    National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA
    BMC Genomics 15:198. 2014
  2. doi request reprint A genomic view of mosaicism and human disease
    Leslie G Biesecker
    National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
    Nat Rev Genet 14:307-20. 2013
  3. pmc Hypothesis-generating research and predictive medicine
    Leslie G Biesecker
    National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
    Genome Res 23:1051-3. 2013
  4. pmc Using exome data to identify malignant hyperthermia susceptibility mutations
    Stephen G Gonsalves
    Research Associate, Clinical Specialty Consultant, Staff Scientist, Branch Chief, Genetic Disease Research Branch, Director, National Institutes of Health Intramural Sequencing Center, National Human Genome Research Institute NHGRI, National Institutes of Health, Bethesda, Maryland Research Associate, Professor of Human Molecular Genetics, Institute of Medical Genetics, School of Medicine, Cardiff University, Heath Park, Cardiff, United Kingdom Postdoctoral Fellow, Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health Current position Assistant Member, H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida Members of the National Institutes of Health Intramural Sequencing Center group are listed in the appendix
    Anesthesiology 119:1043-53. 2013
  5. pmc Secondary variants in individuals undergoing exome sequencing: screening of 572 individuals identifies high-penetrance mutations in cancer-susceptibility genes
    Jennifer J Johnston
    Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Am J Hum Genet 91:97-108. 2012
  6. pmc Interpreting secondary cardiac disease variants in an exome cohort
    David Ng
    Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Circ Cardiovasc Genet 6:337-46. 2013
  7. pmc A mosaic activating mutation in AKT1 associated with the Proteus syndrome
    Marjorie J Lindhurst
    National Human Genome Research Institute, Bethesda, Maryland, USA
    N Engl J Med 365:611-9. 2011
  8. pmc Correlation of rare coding variants in the gene encoding human glucokinase regulatory protein with phenotypic, cellular, and kinetic outcomes
    Matthew G Rees
    National Human Genome Research Institute, NIH, Bethesda, Maryland 20892, USA
    J Clin Invest 122:205-17. 2012
  9. pmc The phenotype of a germline mutation in PIGA: the gene somatically mutated in paroxysmal nocturnal hemoglobinuria
    Jennifer J Johnston
    Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA
    Am J Hum Genet 90:295-300. 2012
  10. pmc Approaches to informed consent for hypothesis-testing and hypothesis-generating clinical genomics research
    Flavia M Facio
    National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA
    BMC Med Genomics 5:45. 2012

Detail Information

Publications43

  1. pmc Identification of candidate genes involved in coronary artery calcification by transcriptome sequencing of cell lines
    Shurjo K Sen
    National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA
    BMC Genomics 15:198. 2014
    ..Here, we used RNA-Seq to study the transcriptomes of matched coronary artery disease cases and controls in the ClinSeq® study, using cell lines as tissue surrogates...
  2. doi request reprint A genomic view of mosaicism and human disease
    Leslie G Biesecker
    National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
    Nat Rev Genet 14:307-20. 2013
    ..Here, we discuss the clinical and molecular classes of mosaicism, their detection and the biological insights gained from these studies...
  3. pmc Hypothesis-generating research and predictive medicine
    Leslie G Biesecker
    National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
    Genome Res 23:1051-3. 2013
    ....
  4. pmc Using exome data to identify malignant hyperthermia susceptibility mutations
    Stephen G Gonsalves
    Research Associate, Clinical Specialty Consultant, Staff Scientist, Branch Chief, Genetic Disease Research Branch, Director, National Institutes of Health Intramural Sequencing Center, National Human Genome Research Institute NHGRI, National Institutes of Health, Bethesda, Maryland Research Associate, Professor of Human Molecular Genetics, Institute of Medical Genetics, School of Medicine, Cardiff University, Heath Park, Cardiff, United Kingdom Postdoctoral Fellow, Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health Current position Assistant Member, H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida Members of the National Institutes of Health Intramural Sequencing Center group are listed in the appendix
    Anesthesiology 119:1043-53. 2013
    ..An unselected cohort was screened for MHS mutations using exome sequencing. The aim of this study was to pilot a strategy for the RYR1 and CACNA1S genes...
  5. pmc Secondary variants in individuals undergoing exome sequencing: screening of 572 individuals identifies high-penetrance mutations in cancer-susceptibility genes
    Jennifer J Johnston
    Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Am J Hum Genet 91:97-108. 2012
    ....
  6. pmc Interpreting secondary cardiac disease variants in an exome cohort
    David Ng
    Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Circ Cardiovasc Genet 6:337-46. 2013
    ..We have piloted a method to analyze exomes to identify participants at risk for cardiac arrhythmias, cardiomyopathies, or sudden death...
  7. pmc A mosaic activating mutation in AKT1 associated with the Proteus syndrome
    Marjorie J Lindhurst
    National Human Genome Research Institute, Bethesda, Maryland, USA
    N Engl J Med 365:611-9. 2011
    ..The Proteus syndrome is characterized by the overgrowth of skin, connective tissue, brain, and other tissues. It has been hypothesized that the syndrome is caused by somatic mosaicism for a mutation that is lethal in the nonmosaic state...
  8. pmc Correlation of rare coding variants in the gene encoding human glucokinase regulatory protein with phenotypic, cellular, and kinetic outcomes
    Matthew G Rees
    National Human Genome Research Institute, NIH, Bethesda, Maryland 20892, USA
    J Clin Invest 122:205-17. 2012
    ..In sum, this study utilizes computational, cell biological, and biochemical methods to present a model for interpreting the clinical significance of rare genetic variants in common disease...
  9. pmc The phenotype of a germline mutation in PIGA: the gene somatically mutated in paroxysmal nocturnal hemoglobinuria
    Jennifer J Johnston
    Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA
    Am J Hum Genet 90:295-300. 2012
    ..We conclude that c.1234C>T in PIGA results in the lethal X-linked phenotype recognized in the reported family...
  10. pmc Approaches to informed consent for hypothesis-testing and hypothesis-generating clinical genomics research
    Flavia M Facio
    National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA
    BMC Med Genomics 5:45. 2012
    ..Massively-parallel sequencing (MPS) technologies create challenges for informed consent of research participants given the enormous scale of the data and the wide range of potential results...
  11. pmc Mosaic overgrowth with fibroadipose hyperplasia is caused by somatic activating mutations in PIK3CA
    Marjorie J Lindhurst
    The National Human Genome Research Institute, US National Institutes of Health, Bethesda, Maryland, USA
    Nat Genet 44:928-33. 2012
    ..Our findings characterize a distinct overgrowth syndrome, biochemically demonstrate activation of PI3K signaling and thereby identify a rational therapeutic target...
  12. pmc Massively parallel sequencing of exons on the X chromosome identifies RBM10 as the gene that causes a syndromic form of cleft palate
    Jennifer J Johnston
    National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892 4472, USA
    Am J Hum Genet 86:743-8. 2010
    ..We conclude that massively parallel sequencing is useful to characterize large candidate linkage intervals and that it can be used successfully to allow identification of disease-causing gene mutations...
  13. pmc Hereditary spastic paraplegia type 43 (SPG43) is caused by mutation in C19orf12
    Guida Landoure
    Service de Neurologie, Centre Hospitalier Universitaire du point G, Bamako, Mali Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland
    Hum Mutat 34:1357-60. 2013
    ....
  14. pmc Integrative DNA, RNA, and Protein Evidence Connects TREML4 to Coronary Artery Calcification
    Shurjo K Sen
    National Human Genome Research Institute, NIH, Bethesda, MD 20892, USA
    Am J Hum Genet 95:66-76. 2014
    ..Overall, we present integrative RNA, DNA, and protein evidence implicating TREML4 in coronary artery calcification. Our findings connect multimodal genomics data with a commonly used clinical marker of cardiovascular disease. ..
  15. pmc Intentions to receive individual results from whole-genome sequencing among participants in the ClinSeq study
    Flavia M Facio
    Social and Behavioral Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA
    Eur J Hum Genet 21:261-5. 2013
    ..It behooves investigators to facilitate participants' desire to learn a range of information from genomic sequencing while promoting realistic expectations for its clinical and personal utility...
  16. ncbi request reprint Clinical delineation and natural history of the PIK3CA-related overgrowth spectrum
    Kim M Keppler-Noreuil
    National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland
    Am J Med Genet A 164:1713-33. 2014
    ..While the current data are consistent with some genotype-phenotype correlation, this cannot yet be confirmed...
  17. pmc Massively-parallel sequencing of genes on a single chromosome: a comparison of solution hybrid selection and flow sorting
    Jamie K Teer
    National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA
    BMC Genomics 14:253. 2013
    ..It is important to understand the advantages, limitations, and complexity of a given capture method before embarking on a targeted sequencing experiment...
  18. pmc Systematic comparison of three genomic enrichment methods for massively parallel DNA sequencing
    Jamie K Teer
    National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
    Genome Res 20:1420-31. 2010
    ..We find that these three genomic enrichment methods are highly accurate and practical, with sensitivities comparable to that of 30-fold coverage whole-genome shotgun data...
  19. pmc Patients with Bardet-Biedl syndrome have hyperleptinemia suggestive of leptin resistance
    Penelope P Feuillan
    Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892 4472, USA
    J Clin Endocrinol Metab 96:E528-35. 2011
    ..To study the pathophysiology of obesity in BBS, we compared patients with BBS and body mass index Z-score (BMI-Z)-matched controls...
  20. pmc VarSifter: visualizing and analyzing exome-scale sequence variation data on a desktop computer
    Jamie K Teer
    National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Bioinformatics 28:599-600. 2012
    ..By simplifying visualization and analyses of exome-scale sequence variation data, this program will help bring the power and promise of massively-parallel DNA sequencing to a broader group of researchers...
  21. pmc Functional analysis of a de novo ACTB mutation in a patient with atypical Baraitser-Winter syndrome
    Jennifer J Johnston
    Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA
    Hum Mutat 34:1242-9. 2013
    ..We present the clinical findings in the patient, comparison of this patient to other patients with ACTB/ACTG1 mutations, and results from actin functional studies that demonstrate novel functional attributes of this mutant protein. ..
  22. pmc Molecular analysis expands the spectrum of phenotypes associated with GLI3 mutations
    Jennifer J Johnston
    Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892 4472, USA
    Hum Mutat 31:1142-54. 2010
    ..Individuals with features of either GCPS or PHS should be screened for mutations in GLI3 even if they do not fulfill clinical criteria...
  23. pmc Recurrence risks for Bardet-Biedl syndrome: Implications of locus heterogeneity
    Julie C Sapp
    National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA
    Genet Med 12:623-7. 2010
    ..The aim of this study was to derive locus-specific recurrence risk estimates for family members of a proband affected with Bardet-Biedl syndrome...
  24. pmc Integrating pharmacogenetic information and clinical decision support into the electronic health record
    Barry R Goldspiel
    Pharmacy Department, National Institutes of Health Clinical Center, Bethesda, Maryland, USA
    J Am Med Inform Assoc 21:522-8. 2014
    ..Prescribers have adapted to using the CDS and have ordered PG testing as a direct result of the implementation. ..
  25. ncbi request reprint Preferences for results delivery from exome sequencing/genome sequencing
    Martha F Wright
    Genetic Disease and Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA
    Genet Med 16:442-7. 2014
    ..The aim of this study was to explore the implications of sequencing information and stated preferences for return of results among research participants...
  26. pmc Validation of My Family Health Portrait for six common heritable conditions
    Flavia M Facio
    National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
    Genet Med 12:370-5. 2010
    ..To assess the ability of My Family Health Portrait to accurately collect family history for six common heritable disorders...
  27. ncbi request reprint Cognitive, sensory, and psychosocial characteristics in patients with Bardet-Biedl syndrome
    Danielle D Brinckman
    Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland
    Am J Med Genet A 161:2964-71. 2013
    ..We identify a characteristic neuro-behavioral profile in our cohort comprised of reduced IQ, impaired fine-motor function, and decreased olfaction...
  28. pmc Extending the spectrum of Ellis van Creveld syndrome: a large family with a mild mutation in the EVC gene
    Hakan Ulucan
    Genetic Disease Research Branch, National Human Genome Research Institute, NIH, Bethesda, MD, USA
    BMC Med Genet 9:92. 2008
    ..The phenotype was inherited in an autosomal recessive pattern, with one instance of pseudodominant inheritance...
  29. pmc Incidental variants are critical for genomics
    Leslie G Biesecker
    National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Am J Hum Genet 92:648-51. 2013
    ..As a field, we should take full advantage of all opportunities to study these variants by searching them out, returning them to patients and research participants, and studying their utility for predictive medicine...
  30. doi request reprint Expansion of the TARP syndrome phenotype associated with de novo mutations and mosaicism
    Jennifer J Johnston
    Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland
    Am J Med Genet A 164:120-8. 2014
    ..All three families demonstrated de novo mutations, and one of the families had two recurrences, with demonstrable maternal mosaicism...
  31. pmc Motivators for participation in a whole-genome sequencing study: implications for translational genomics research
    Flavia M Facio
    National Human Genome Research Institute, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA
    Eur J Hum Genet 19:1213-7. 2011
    ....
  32. pmc Cowchock syndrome is associated with a mutation in apoptosis-inducing factor
    Carlo Rinaldi
    Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892 3705, USA
    Am J Hum Genet 91:1095-102. 2012
    ..Our findings expand the spectrum of AIF-related disease and provide insight into the effects of AIFM1 mutations...
  33. pmc Polydactyly: how many disorders and how many genes? 2010 update
    Leslie G Biesecker
    Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA
    Dev Dyn 240:931-42. 2011
    ..These results show that knowledge of limb patterning genetics is improving rapidly. Soon, we will have a comprehensive toolkit of genes important for limb development, which will lead to regenerative therapies for limb anomalies...
  34. pmc Opportunities and challenges for the integration of massively parallel genomic sequencing into clinical practice: lessons from the ClinSeq project
    Leslie G Biesecker
    Genetic Disease Research Branch and National Institutes of Health Intramural Sequencing Center, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA
    Genet Med 14:393-8. 2012
    ..This article outlines the main biomedical considerations of sequencing technologies and demonstrates some of the early clinical experiences with the technology to enable the debate to stay focused on real-world practicalities...
  35. pmc Exome sequencing identifies ACSF3 as a cause of combined malonic and methylmalonic aciduria
    Jennifer L Sloan
    Genetics and Molecular Biology Branch, National Human Genome Research Institute, US National Institutes of Health, Bethesda, Maryland, USA
    Nat Genet 43:883-6. 2011
    ....
  36. pmc FOS expression in blood as a LDL-independent marker of statin treatment
    Ju Gyeong Kang
    Translational Medicine Branch, Cardiology Section National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Atherosclerosis 212:567-70. 2010
    ..In this pilot study, we hypothesized that blood FOS mRNA levels will be sensitive to statin treatment independent of LDL cholesterol levels...
  37. pmc An introduction to standardized clinical nomenclature for dysmorphic features: the Elements of Morphology project
    Leslie G Biesecker
    Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA
    BMC Med 8:56. 2010
    ..Here, the background to the project, progress to date, and the practical implementation of the terminology in research reporting is discussed...
  38. pmc Elements of morphology: standard terminology for the hands and feet
    Leslie G Biesecker
    National Human Genome Research Institute, NIH, Bethesda, Maryland 20892 4472, USA
    Am J Med Genet A 149:93-127. 2009
    ..Here we introduce the anatomy of the hands and feet and define and illustrate the terms that describe the major characteristics of the hands and feet...
  39. pmc A candidate gene for autoimmune myasthenia gravis
    Guida Landoure
    Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA
    Neurology 79:342-7. 2012
    ..We sought to identify a causative mutation in a previously reported kindred with parental consanguinity and 5 of 10 siblings with adult-onset autoimmune myasthenia gravis...
  40. pmc The ClinSeq Project: piloting large-scale genome sequencing for research in genomic medicine
    Leslie G Biesecker
    National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
    Genome Res 19:1665-74. 2009
    ..The early experiences with ClinSeq illustrate how large-scale medical sequencing can be a practical, productive, and critical component of research in genomic medicine...
  41. pmc Assessment and management of the orthopedic and other complications of Proteus syndrome
    Laura L Tosi
    Division of Orthopaedic Surgery and Sports Medicine, Children s National Medical Center, 111 Michigan Avenue, NW, Washington, DC 20010 USA Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD USA
    J Child Orthop 5:319-27. 2011
    ..While PS poses many complex challenges, the focus of the workshop was the management of the asymmetric and disorganized skeletal overgrowth that characterizes this multisystem disorder...
  42. pmc Next-generation sequencing in the clinic: are we ready?
    Leslie G Biesecker
    Genetic Disease Research Branch, National Human Genome Research Institute, 49 Convent Drive, Room 4A56, Bethesda, Maryland 20892, USA
    Nat Rev Genet 13:818-24. 2012
    ..Here, we ask five experts to give their opinions on whether clinical data should be treated differently from other medical data, given the potential use of these tests, and on the areas that must be developed to improve patient outcome...
  43. pmc Progressive overgrowth of the cerebriform connective tissue nevus in patients with Proteus syndrome
    Thomas M Beachkofsky
    Department of Dermatology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814, USA
    J Am Acad Dermatol 63:799-804. 2010
    ..Proteus syndrome is a rare overgrowth disorder that almost always affects the skin...