Charles Dunlop - Academia.edu (original) (raw)

Papers by Charles Dunlop

Research paper thumbnail of A cortical neuropeptide with neuronal depressant and sleep-modulating properties

Research paper thumbnail of Not All Next Generation Sequencing Diagnostics are Created Equal: Understanding the Nuances of Solid Tumor Assay Design for Somatic Mutation Detection

Cancers, 2015

The molecular characterization of tumors using next generation sequencing (NGS) is an emerging di... more The molecular characterization of tumors using next generation sequencing (NGS) is an emerging diagnostic tool that is quickly becoming an integral part of clinical decision making. Cancer genomic profiling involves significant challenges including DNA quality and quantity, tumor heterogeneity, and the need to detect a wide variety of complex genetic mutations. Most available comprehensive diagnostic tests rely on primer based amplification or probe based capture methods coupled with NGS to detect hotspot mutation sites or whole regions implicated in disease. These tumor panels utilize highly customized bioinformatics pipelines to perform the difficult task of accurately calling cancer relevant alterations such as single nucleotide variations, small indels or large genomic alterations from the NGS data. In this review, we will discuss the challenges of solid tumor assay design/analysis and report a case study that highlights the need to include complementary technologies (i.e., arrays) and germline analysis in tumor testing to reliably identify copy number alterations and actionable variants.

Research paper thumbnail of Responses to “The consequences of computing”

ACM SIGCAS Computers and Society, 1996

Research paper thumbnail of 21.18 Carbon dioxide angiography can be performed simply and efficaciously

Cardiovascular Surgery, 1997

Femoropopliteal I multisegmental graft stenoses requiring revision. The remaining five grafts wer... more Femoropopliteal I multisegmental graft stenoses requiring revision. The remaining five grafts were patent with a mean follow-up of 9.5 months.

Research paper thumbnail of Arteriography in chronic renal failure: a case for carbon dioxide

Cardiovascular Surgery, 1999

Purpose: The aim of this study was to assess the utilisation of carbon dioxide arteriography, per... more Purpose: The aim of this study was to assess the utilisation of carbon dioxide arteriography, performed with a simple injection system, as the imaging technique of choice in patients with chronic renal failure. Methods: Patients with chronic renal impairment who required arterial imaging or intervention were recruited for carbon dioxide angiography. Demographic data were prospectively recorded and pre-and post-arteriogram renal function was quantified. Radiographic images were graded by an independent radiologist. Results: Twenty-eight patients underwent renal or aorto-femoral studies with only one failure. There were no cases of contrast-induced nephropathy. Twenty-two of the films (79%) were graded as excellent or good, four as acceptable and two were considered to be poor (non-diagnostic). Conclusions: This study has demonstrated that carbon dioxide angiography is a safe and clinically effective procedure in patients with chronic renal failure.

Research paper thumbnail of Book reviews and critical studies

Research paper thumbnail of Approaches to identifying mutations associated with hereditary nonpolyposis colorectal cancer

Research paper thumbnail of Molecular Genetic Diagnostic System

Research paper thumbnail of Hereditary predisposition to ovarian cancer, looking beyond BRCA1/BRCA2

Gynecologic Oncology, 2014

Genetic predisposition to ovarian cancer is well documented. With the advent of next generation s... more Genetic predisposition to ovarian cancer is well documented. With the advent of next generation sequencing, hereditary panel testing provides an efficient method for evaluating multiple genes simultaneously. Therefore, we sought to investigate the contribution of 19 genes identified in the literature as increasing the risk of hereditary breast and ovarian cancer (HBOC) in a BRCA1 and BRCA2 negative population of patients with a personal history of breast and/or ovarian cancer by means of a hereditary cancer panel. Subjects were referred for multi-gene panel testing between February 2012 and March 2014. Clinical data was ascertained from requisition forms. The incidence of pathogenic mutations (including likely pathogenic), and variant of unknown significance were then calculated for each gene and/or patient cohort. In this cohort of 911 subjects, panel testing identified 67 mutations. With 7.4% of subjects harboring a mutation on this multi-gene panel, the diagnostic yield was increased, compared to testing for BRCA1 and BRCA2 mutations alone. In the ovarian cancer probands, the most frequently mutated genes were BRIP1 (n=8; 1.72%) and MSH6 (n=6; 1.29%). In the breast cancer probands, mutations were most commonly observed in CHEK2 (n=9; 2.54%), ATM (n=3; 0.85%), and TP53 (n=3; 0.85%). Although further studies are needed to clarify the exact management of patients with a mutation in each gene, this study highlights information that can be captured with panel testing and provides support for incorporation of panel testing into clinical practice.

Research paper thumbnail of Enhanced utility of family-centered diagnostic exome sequencing with inheritance model–based analysis: results from 500 unselected families with undiagnosed genetic conditions

Genetics in Medicine, 2014

Research paper thumbnail of 20.17 Are incompetent calf perforating veins haemodynamically significant?

Cardiovascular Surgery, 1997

Research paper thumbnail of Diagnostic Testing by CFTR Gene Mutation Analysis in a Large Group of Hispanics

The Journal of Molecular Diagnostics, 2005

Characterization of CFTR mutations in the U.S. Hispanic population is vital to early diagnosis, g... more Characterization of CFTR mutations in the U.S. Hispanic population is vital to early diagnosis, genetic counseling, patient-specific treatment, and the understanding of cystic fibrosis (CF) pathogenesis. The mutation spectrum in Hispanics, however, remains poorly defined. A group of 257 self-identified Hispanics with clinical manifestations consistent with CF were studied by temporal temperature gradient electrophoresis and/or DNA sequencing. A total of 183 mutations were identified, including 14 different amino acid-changing novel variants. A significant proportion (78/85) of the different mutations identified would not have been detected by the ACMG/ ACOG-recommended 25-mutation screening panel. Over one third of the mutations (27/85) occurred with a relative frequency >1%, which illustrates that the identified mutations are not all rare. This is supported by a comparison with other large CFTR studies. These results underscore the disparity in mutation identification between Caucasians and Hispanics and show utility for comprehensive diagnostic CFTR mutation analysis in this population. Address reprint requests to Iris Schrijver M.D.,

Research paper thumbnail of Elevated serum eosinophilic cationic protein (ECP) does not predict exacerbation in stable asthmatic children

Research paper thumbnail of A cortical neuropeptide with neuronal depressant and sleep-modulating properties

Research paper thumbnail of Comprehensive genetic analysis of the cystic fibrosis transmembrane conductance regulator from dried blood specimens – Implications for newborn screening

Genetics in Medicine, 2006

In the United States, approximately 1/3,700 babies is born with cystic fibrosis each year. The &a... more In the United States, approximately 1/3,700 babies is born with cystic fibrosis each year. The >1,300 documented sequence variants pose a challenge for detection of cystic fibrosis through genetic screening. To investigate whether comprehensive characterization of the cystic fibrosis gene is feasible using dried newborn blood specimens, we modified the whole blood Ambry Test: CF and determined its sensitivity by testing DNA from individuals with cystic fibrosis who still had unknown mutations after commercial mutation panel testing. DNA from 42 archived newborn dried blood specimens of affected Hispanic, African-American and Caucasian individuals in California was analyzed by temporal temperature gradient electrophoresis screening and targeted sequencing, and by gross deletion analysis. Excluding two specimens that could not be analyzed due to poor DNA quality, we report a 100% sensitivity and clinical detection rate in the remaining 40 patients. Eighty-three mutations representing 40 different variants were detected, including 8 novel mutations. This study demonstrates the feasibility of temporal temperature gradient electrophoresis-based full sequence analysis and targeted sequencing from DNA in newborn blood specimens. The Ambry Test: CF, as an additional step in cystic fibrosis newborn screening models, can be used to dramatically reduce the number of cystic fibrosis carrier sweat test referrals.

Research paper thumbnail of A Prospective Randomized Trial Evaluating the Haemodynamic Role of Incompetent Calf Perforating Veins

ANZ Journal of Surgery, 1999

This study was undertaken to determine the haemodynamic effect of incompetent calf perforating ve... more This study was undertaken to determine the haemodynamic effect of incompetent calf perforating veins in patients with uncomplicated varicose veins and long saphenous incompetence. Thirty-eight limbs from 35 patients were studied. All patients had uncomplicated varicose veins with both long saphenous and calf perforator incompetence on duplex ultrasonography. Patients were randomized to have incompetent calf perforators ligated or left intact, in addition to saphenofemoral junction ligation, strip of long saphenous vein to knee and stab avulsion of any visible varicosities in the leg. Patients were assessed with air plethysmography pre-operatively and 3 months postoperatively. Superficial venous surgery improved venous volume, venous filling index and ejection fraction in the patient cohort. No significant haemodynamic difference was demonstrated between the two groups of patients who were randomized. At present, the results of this study do not support the use of routine perforator ligation during superficial surgery for uncomplicated varicose veins.

Research paper thumbnail of Glossary of cognitive science

An academic directory and search engine.

Research paper thumbnail of A cortical neuropeptide with neuronal depressant and sleep-modulating properties

Research paper thumbnail of Not All Next Generation Sequencing Diagnostics are Created Equal: Understanding the Nuances of Solid Tumor Assay Design for Somatic Mutation Detection

Cancers, 2015

The molecular characterization of tumors using next generation sequencing (NGS) is an emerging di... more The molecular characterization of tumors using next generation sequencing (NGS) is an emerging diagnostic tool that is quickly becoming an integral part of clinical decision making. Cancer genomic profiling involves significant challenges including DNA quality and quantity, tumor heterogeneity, and the need to detect a wide variety of complex genetic mutations. Most available comprehensive diagnostic tests rely on primer based amplification or probe based capture methods coupled with NGS to detect hotspot mutation sites or whole regions implicated in disease. These tumor panels utilize highly customized bioinformatics pipelines to perform the difficult task of accurately calling cancer relevant alterations such as single nucleotide variations, small indels or large genomic alterations from the NGS data. In this review, we will discuss the challenges of solid tumor assay design/analysis and report a case study that highlights the need to include complementary technologies (i.e., arrays) and germline analysis in tumor testing to reliably identify copy number alterations and actionable variants.

Research paper thumbnail of Responses to “The consequences of computing”

ACM SIGCAS Computers and Society, 1996

Research paper thumbnail of 21.18 Carbon dioxide angiography can be performed simply and efficaciously

Cardiovascular Surgery, 1997

Femoropopliteal I multisegmental graft stenoses requiring revision. The remaining five grafts wer... more Femoropopliteal I multisegmental graft stenoses requiring revision. The remaining five grafts were patent with a mean follow-up of 9.5 months.

Research paper thumbnail of Arteriography in chronic renal failure: a case for carbon dioxide

Cardiovascular Surgery, 1999

Purpose: The aim of this study was to assess the utilisation of carbon dioxide arteriography, per... more Purpose: The aim of this study was to assess the utilisation of carbon dioxide arteriography, performed with a simple injection system, as the imaging technique of choice in patients with chronic renal failure. Methods: Patients with chronic renal impairment who required arterial imaging or intervention were recruited for carbon dioxide angiography. Demographic data were prospectively recorded and pre-and post-arteriogram renal function was quantified. Radiographic images were graded by an independent radiologist. Results: Twenty-eight patients underwent renal or aorto-femoral studies with only one failure. There were no cases of contrast-induced nephropathy. Twenty-two of the films (79%) were graded as excellent or good, four as acceptable and two were considered to be poor (non-diagnostic). Conclusions: This study has demonstrated that carbon dioxide angiography is a safe and clinically effective procedure in patients with chronic renal failure.

Research paper thumbnail of Book reviews and critical studies

Research paper thumbnail of Approaches to identifying mutations associated with hereditary nonpolyposis colorectal cancer

Research paper thumbnail of Molecular Genetic Diagnostic System

Research paper thumbnail of Hereditary predisposition to ovarian cancer, looking beyond BRCA1/BRCA2

Gynecologic Oncology, 2014

Genetic predisposition to ovarian cancer is well documented. With the advent of next generation s... more Genetic predisposition to ovarian cancer is well documented. With the advent of next generation sequencing, hereditary panel testing provides an efficient method for evaluating multiple genes simultaneously. Therefore, we sought to investigate the contribution of 19 genes identified in the literature as increasing the risk of hereditary breast and ovarian cancer (HBOC) in a BRCA1 and BRCA2 negative population of patients with a personal history of breast and/or ovarian cancer by means of a hereditary cancer panel. Subjects were referred for multi-gene panel testing between February 2012 and March 2014. Clinical data was ascertained from requisition forms. The incidence of pathogenic mutations (including likely pathogenic), and variant of unknown significance were then calculated for each gene and/or patient cohort. In this cohort of 911 subjects, panel testing identified 67 mutations. With 7.4% of subjects harboring a mutation on this multi-gene panel, the diagnostic yield was increased, compared to testing for BRCA1 and BRCA2 mutations alone. In the ovarian cancer probands, the most frequently mutated genes were BRIP1 (n=8; 1.72%) and MSH6 (n=6; 1.29%). In the breast cancer probands, mutations were most commonly observed in CHEK2 (n=9; 2.54%), ATM (n=3; 0.85%), and TP53 (n=3; 0.85%). Although further studies are needed to clarify the exact management of patients with a mutation in each gene, this study highlights information that can be captured with panel testing and provides support for incorporation of panel testing into clinical practice.

Research paper thumbnail of Enhanced utility of family-centered diagnostic exome sequencing with inheritance model–based analysis: results from 500 unselected families with undiagnosed genetic conditions

Genetics in Medicine, 2014

Research paper thumbnail of 20.17 Are incompetent calf perforating veins haemodynamically significant?

Cardiovascular Surgery, 1997

Research paper thumbnail of Diagnostic Testing by CFTR Gene Mutation Analysis in a Large Group of Hispanics

The Journal of Molecular Diagnostics, 2005

Characterization of CFTR mutations in the U.S. Hispanic population is vital to early diagnosis, g... more Characterization of CFTR mutations in the U.S. Hispanic population is vital to early diagnosis, genetic counseling, patient-specific treatment, and the understanding of cystic fibrosis (CF) pathogenesis. The mutation spectrum in Hispanics, however, remains poorly defined. A group of 257 self-identified Hispanics with clinical manifestations consistent with CF were studied by temporal temperature gradient electrophoresis and/or DNA sequencing. A total of 183 mutations were identified, including 14 different amino acid-changing novel variants. A significant proportion (78/85) of the different mutations identified would not have been detected by the ACMG/ ACOG-recommended 25-mutation screening panel. Over one third of the mutations (27/85) occurred with a relative frequency >1%, which illustrates that the identified mutations are not all rare. This is supported by a comparison with other large CFTR studies. These results underscore the disparity in mutation identification between Caucasians and Hispanics and show utility for comprehensive diagnostic CFTR mutation analysis in this population. Address reprint requests to Iris Schrijver M.D.,

Research paper thumbnail of Elevated serum eosinophilic cationic protein (ECP) does not predict exacerbation in stable asthmatic children

Research paper thumbnail of A cortical neuropeptide with neuronal depressant and sleep-modulating properties

Research paper thumbnail of Comprehensive genetic analysis of the cystic fibrosis transmembrane conductance regulator from dried blood specimens – Implications for newborn screening

Genetics in Medicine, 2006

In the United States, approximately 1/3,700 babies is born with cystic fibrosis each year. The &a... more In the United States, approximately 1/3,700 babies is born with cystic fibrosis each year. The >1,300 documented sequence variants pose a challenge for detection of cystic fibrosis through genetic screening. To investigate whether comprehensive characterization of the cystic fibrosis gene is feasible using dried newborn blood specimens, we modified the whole blood Ambry Test: CF and determined its sensitivity by testing DNA from individuals with cystic fibrosis who still had unknown mutations after commercial mutation panel testing. DNA from 42 archived newborn dried blood specimens of affected Hispanic, African-American and Caucasian individuals in California was analyzed by temporal temperature gradient electrophoresis screening and targeted sequencing, and by gross deletion analysis. Excluding two specimens that could not be analyzed due to poor DNA quality, we report a 100% sensitivity and clinical detection rate in the remaining 40 patients. Eighty-three mutations representing 40 different variants were detected, including 8 novel mutations. This study demonstrates the feasibility of temporal temperature gradient electrophoresis-based full sequence analysis and targeted sequencing from DNA in newborn blood specimens. The Ambry Test: CF, as an additional step in cystic fibrosis newborn screening models, can be used to dramatically reduce the number of cystic fibrosis carrier sweat test referrals.

Research paper thumbnail of A Prospective Randomized Trial Evaluating the Haemodynamic Role of Incompetent Calf Perforating Veins

ANZ Journal of Surgery, 1999

This study was undertaken to determine the haemodynamic effect of incompetent calf perforating ve... more This study was undertaken to determine the haemodynamic effect of incompetent calf perforating veins in patients with uncomplicated varicose veins and long saphenous incompetence. Thirty-eight limbs from 35 patients were studied. All patients had uncomplicated varicose veins with both long saphenous and calf perforator incompetence on duplex ultrasonography. Patients were randomized to have incompetent calf perforators ligated or left intact, in addition to saphenofemoral junction ligation, strip of long saphenous vein to knee and stab avulsion of any visible varicosities in the leg. Patients were assessed with air plethysmography pre-operatively and 3 months postoperatively. Superficial venous surgery improved venous volume, venous filling index and ejection fraction in the patient cohort. No significant haemodynamic difference was demonstrated between the two groups of patients who were randomized. At present, the results of this study do not support the use of routine perforator ligation during superficial surgery for uncomplicated varicose veins.

Research paper thumbnail of Glossary of cognitive science

An academic directory and search engine.