142 results on '"Campbell, Ian M."'
Search Results
102. Studies of reactions of atoms in a discharge flow stirred reactor. Part 2.―O+H2+CO system.
- Author
-
Campbell, Ian M. and Handy, Brian J.
- Published
- 1978
- Full Text
- View/download PDF
103. Studies of reactions of atoms in a discharge flow stirred reactor. Part 3.―The O + H2+ O2 system.
- Author
-
Campbell, Ian M., Rogerson, John S., and Handy, Brian J.
- Published
- 1978
- Full Text
- View/download PDF
104. Studies of reactions of atoms in a discharge flow stirred reactor. Part 1.―The O + H2+ NO system.
- Author
-
Campbell, Ian M. and Handy, Brian J.
- Published
- 1975
- Full Text
- View/download PDF
105. Biologically Active Phytoestrogens Are Present in Bourbon.
- Author
-
Gavaler, Judith S., Rosenblum, Elaine R, Thiel, David H., Eagon, Patricia K, Pohl, Clifford R, Campbell, Ian M, and Gavaler, Joan
- Abstract
The nonethanol congeners of bourbon have been found to possess estrogenic activity when tested using an in vivo oophorectomized rat bioassay, as well as an in vitro estrogen receptor assay system. The phytoestrogen, biochanin A, as well as the plant sterol, β-sitosterol, were identified in the bourbon preparation using gas chromatography/mass spectrometry. These findings, using three methodological approaches, demonstrate that bourbon contains at least one biologically active phytoestrogen and suggest that the effects of alcoholic beverage use or abuse, particularly as they relate to endocrine systems, should not be viewed as resulting solely from exposure to ethanol. [ABSTRACT FROM AUTHOR]
- Published
- 1987
- Full Text
- View/download PDF
106. Relative rates of reaction of hydroxyl radicals with O(3P) atoms and CO molecules
- Author
-
Campbell, Ian M. and Handy, Brian J.
- Abstract
The rates of decay of O(3P) atoms in H2/CO/N2mixtures in a discharge flow system have been measured, using O + CO chemiluminescence. The mechanism is: O + H2→ OH + H (1), O + OH → O2+ H (2), CO + OH → CO2+ H (3). At 425 K, k2/k3= 260 ± 20; literature values of k3combine to yield k2= (2.65 ± 0.52) × 1010dm3mol−1s−1.
- Published
- 1977
- Full Text
- View/download PDF
107. Utility of the GdScale for the Measurement of Gender-Dysphoria in Males
- Author
-
Ross, Michael W., Burnard, Don, and Campbell, Ian M.
- Abstract
Responses on the 31-item Gender Dysphoria (Gd) scale of the MMPI of 104 primary gender-dysphoric males who had undergone or were about to undergo gender-reassignment surgery, 25 secondary gender-dysphoric patients from the same clinics, and 563 male psychiatric outpatients were tabulated and specificities and sensitivities calculated. The scale had satisfactory specificity, correctly identifying 98.1% of subjects. Sensitivity was unsatisfactory (40%) in distinguishing secondary gender-dysphorics in the Gender Clinic samples but adequate (88.4%) in the combined psychiatric outpatient and Gender Clinic samples. Factor analysis yielded 8 dimensions, but only 2 of these were easily interpretable or had sufficient items to ensure reliability, suggesting that there was little possibility of utilizing subscales. It is concluded that the Gdscale is an appropriate instrument for excluding primary gender dysphoria when used in conjunction with conventional diagnostic assessments.
- Published
- 1988
- Full Text
- View/download PDF
108. A new method for the synthesis of nitroethane, ethyl nitrite, and ethyl nitrate.
- Author
-
Audley, Gary J., Baulch, Donald L., and Campbell, Ian M.
- Published
- 1982
- Full Text
- View/download PDF
109. Studies of reactions of atoms in a discharge-flow stirred reactor. Part 5.—O(3P)+ trimethylamine
- Author
-
Baulch, Donald L., primary, Campbell, Ian M., additional, and Hainsworth, Robert, additional
- Published
- 1984
- Full Text
- View/download PDF
110. Reversible cryogenic alteration of the ultraviolet absorption spectra of the olefinic bonds in lipid membranes
- Author
-
Campbell, Ian M., primary and Pawagi, Asha B., additional
- Published
- 1982
- Full Text
- View/download PDF
111. The rate constants for the reaction of the hydroxyl radical with methyl, n‐propyl, and n‐butyl nitrites
- Author
-
Baulch, Donald L., primary, Campbell, Ian M., additional, and Saunders, Sandra M., additional
- Published
- 1985
- Full Text
- View/download PDF
112. Rate constants for reactions of hydroxyl radicals with ester vapours at 292 K
- Author
-
Campbell, Ian M., primary and Parkinson, Paul E., additional
- Published
- 1978
- Full Text
- View/download PDF
113. Utility of the Gd Scale for the Measurement of Gender-Dysphoria in Males
- Author
-
Ross, Michael W., primary, Burnard, Don, additional, and Campbell, Ian M., additional
- Published
- 1988
- Full Text
- View/download PDF
114. The Stress Is on Anxiety
- Author
-
Campbell, Ian M., primary
- Published
- 1981
- Full Text
- View/download PDF
115. Evidence for a new intermediate in N2O5 decomposition
- Author
-
Audley, Gary J., primary, Baulch, Donald L., additional, Campbell, Ian M., additional, and Hamill, L. Tom, additional
- Published
- 1980
- Full Text
- View/download PDF
116. Is social skills performance a correlate of schizophrenia subtypes?
- Author
-
Jackson, Henry J., primary, Minas, Iraklis H., additional, Burgess, Philip M., additional, Joshua, Stephen D., additional, Charisiou, James, additional, and Campbell, Ian M., additional
- Published
- 1989
- Full Text
- View/download PDF
117. The effect of polypeptide–lipid interactions on the ultraviolet spectrum of the olefinic bonds of the lipid
- Author
-
Campbell, Ian M., primary and Pawagi, Asha B., additional
- Published
- 1980
- Full Text
- View/download PDF
118. The excitation of chlorine in active nitrogen
- Author
-
Black, Graham, primary and Campbell, Ian M., additional
- Published
- 1978
- Full Text
- View/download PDF
119. Changes in the osmotic behaviour of phosphatidylcholine vesicles induced by interaction with polyamino acids
- Author
-
Chwang, Willy K., primary, Pawagi, Asha, additional, and Campbell, Ian M., additional
- Published
- 1979
- Full Text
- View/download PDF
120. Vesicle surface charge and polylysine modification of ultraviolet absorption by the olefinic bonds in charged lipid
- Author
-
Pawagi, Asha B., primary and Campbell, Ian M., additional
- Published
- 1981
- Full Text
- View/download PDF
121. Temperature-dependent interactions between poly-L-lysine and phosphatidylcholine vesicles
- Author
-
Campbell, Ian M., primary and Pawagi, Asha B., additional
- Published
- 1979
- Full Text
- View/download PDF
122. Leslie Mitchell: Lewis Grassic Gibbon.
- Author
-
Campbell, Ian M.
- Published
- 1967
123. Reviews of books.
- Author
-
Campbell, Ian M. and Bell, R. P.
- Published
- 1971
- Full Text
- View/download PDF
124. Differential Transit Peptide Recognition during Preprotein Binding and Translocation into Flowering Plant Plastids.
- Author
-
Chotewutmontri, Prakitchai, Reddick, L. Evan, McWilliams, David R., Campbell, Ian M., and Bruce, Barry D.
- Subjects
- *
PLANT translocation , *FLOWERING of plants , *PEPTIDES , *PLASTIDS , *MOLECULAR motor proteins - Abstract
Despite the availability of thousands of transit peptide (TP) primary sequences, the structural and/or physicochemical properties that determine TP recognition by components of the chloroplast translocon are not well understood. By combining a series of in vitro and in vivo experiments, we reveal that TP recognition is determined by sequence-independent interactions and vectorial-specific recognition domains. Using both native and reversed TPs for two well-studied precursors, small subunit of ribulose-1,5-bis-phosphate carboxylase/oxygenase, and ferredoxin, we exposed these two modes of recognition. Toc34 receptor (34-kD subunit of the translocon of the outer envelope) recognition in vitro, preprotein binding in organellar, precursor binding in vivo, and the recognition of TPs by the major stromal molecular motor Hsp70 are specific for the physicochemical properties of the TP. However, translocation in organellar and in vivo demonstrates strong specificity to recognition domain organization. This organization specificity correlates with the N-terminal placement of a strong Hsp70 recognition element. These results are discussed in light of how individual translocon components sequentially interact with the precursor during binding and translocation and helps explain the apparent lack of sequence conservation in chloroplast TPs. [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
- View/download PDF
125. Genes that Affect Brain Structure and Function Identified by Rare Variant Analyses of Mendelian Neurologic Disease
- Author
-
Asuman Koparir, Ender Karaca, Tulay Guran, Nursel Elcioglu, Salih Coşkun, Özlem Sezer, Sevcan Tug Bozdogan, Alper Han Cebi, Jill V. Hunter, James R. Lupski, Shalini N. Jhangiani, Sedat Işıkay, Hatip Aydin, Erkan Koparir, Dilek Aktas, Adnan Yuksel, Davut Gul, Mehmed M. Atik, Burak Durmaz, Mehmet Ture, Ian M. Campbell, Wendy K. Chung, Tamar Harel, Emre Kirat, Mahmut Selman Yildirim, Ayse Aksoy, Mehmet Bugrahan Duz, John D. Overton, Tulay Tos, Claudia Gonzaga-Jauregui, Darryl C. De Vivo, Yavuz Bayram, Kadri Karaer, Gozde Yesil, Wojciech Wiszniewski, Davut Pehlivan, Eric Boerwinkle, Huseyin Aslan, Hakan Ulucan, Ozgur Cogulu, Fatma Ekici, Vehap Topcu, Elif Fenercioglu, Mehmet Seven, Alper Gezdirici, Salih Cicek, Tomasz Gambin, Tahsin Yakut, Mustafa Ozen, Mevlit Ikbal, Donna M. Muzny, Zeynep Coban Akdemir, Elif Yilmaz Gulec, Preti Jain, Bilge Geckinli, Sukru Candan, Richard A. Gibbs, Serkan Erdin, Mehmet Alikasifoglu, Ozge Ozalp Yuregir, Ferda Ozkinay, Hilde Van Esch, David R. Adams, Bo Yuan, YEŞİL, Gözde, Ege Üniversitesi, Biruni Üniversitesi, Karaca, Ender, Harel, Tamar, Pehlivan, Davut, Jhangiani, Shalini N., Gambin, Tomasz, Akdemir, Zeynep Coban, Gonzaga-Jauregui, Claudia, Erdin, Serkan, Bayram, Yavuz, Campbell, Ian M., Hunter, Jill V., Atik, Mehmed M., Van Esch, Hilde, Yuan, Bo, Wiszniewski, Wojciech, Isikay, Sedat, Yesil, Gozde, Yuregir, Ozge O., Bozdogan, Sevcan Tug, Aslan, Huseyin, Aydin, Hatip, Tos, Tulay, Aksoy, Ayse, De Vivo, Darryl C., Jain, Preti, Geckinli, B. Bilge, Sezer, Ozlem, Gul, Davut, Durmaz, Burak, Cogulu, Ozgur, Ozkinay, Ferda, Topcu, Vehap, Candan, Sukru, Cebi, Alper Han, Ikbal, Mevlit, Gulec, Elif Yilmaz, Gezdirici, Alper, Koparir, Erkan, Ekici, Fatma, Coskun, Salih, Cicek, Salih, Karaer, Kadri, Koparir, Asuman, Duz, Mehmet Bugrahan, Kirat, Emre, Fenercioglu, Elif, Ulucan, Hakan, Seven, Mehmet, Guran, Tulay, Elcioglu, Nursel, Yildirim, Mahmut Selman, Aktas, Dilek, Alikasifoglu, Mehmet, Ture, Mehmet, Yakut, Tahsin, Overton, John D., Yuksel, Adnan, Ozen, Mustafa, Muzny, Donna M., Adams, David R., Boerwinkle, Eric, Chung, Wendy K., Gibbs, Richard A., and Lupski, James R.
- Subjects
Male ,PONTOCEREBELLAR HYPOPLASIA ,Candidate gene ,Rna Helicases ,PROTEIN ,Cohort Studies ,0302 clinical medicine ,Snx14 Cause ,Databases, Genetic ,Gene Regulatory Networks ,Copy-number variation ,Pontocerebellar Hypoplasia ,Exome sequencing ,Alzheimers-Disease ,Genetics ,0303 health sciences ,H-Prune ,General Neuroscience ,Brain ,Mendelian Randomization Analysis ,Neurologic Disease ,Pedigree ,3. Good health ,ALZHEIMERS-DISEASE ,H-PRUNE ,symbols ,Female ,Mutations ,Neuroscience(all) ,SNX14 CAUSE ,Biology ,TRIPLE T COMPLEX ,Article ,03 medical and health sciences ,symbols.namesake ,Genetic variation ,CHROMATIN REMODELING COMPLEX ,Humans ,Allele ,Gene ,Genetic Association Studies ,030304 developmental biology ,RNA HELICASES ,MUTATIONS ,Protein ,Genetic Variation ,Triple T Complex ,INTELLECTUAL-DISABILITY SYNDROME ,Intellectual-Disability Syndrome ,Mendelian inheritance ,Chromatin Remodeling Complex ,Nervous System Diseases ,030217 neurology & neurosurgery - Abstract
WOS: 000365765400011, PubMed ID: 26539891, Development of the human nervous system involves complex interactions among fundamental cellular processes and requires a multitude of genes, many of which remain to be associated with human disease. We applied whole exome sequencing to 128 mostly consanguineous families with neurogenetic disorders that often included brain malformations. Rare variant analyses for both single nucleotide variant (SNV) and copy number variant (CNV) alleles allowed for identification of 45 novel variants in 43 known disease genes, 41 candidate genes, and CNVs in 10 families, with an overall potential molecular cause identified in >85% of families studied. Among the candidate genes identified, we found PRUNE, VARS, and DHX37 in multiple families and homozygous loss-of-function variants in AGBL2, SLC18A2, SMARCA1, UBQLN1, and CPLX1. Neuroimaging and in silico analysis of functional and expression proximity between candidate and known disease genes allowed for further understanding of genetic networks underlying specific types of brain malformations., U.S. National Human Genome Research Institute (NHGRI) NHLBI grant [U54HG006542]; NINDSUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Neurological Disorders & Stroke (NINDS) [RO1 NS058529, K23NS078056]; NHGRIUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Human Genome Research Institute (NHGRI) [5U54HG003273]; Medical Genetics Research Fellowship Program [T32 GM07526]; Regeneron, We thank all the family members and collaborators who participated in this study. This work was supported by U.S. National Human Genome Research Institute (NHGRI) NHLBI grant U54HG006542 to the Baylor-Hopkins Center for Mendelian Genomics, NINDS grant RO1 NS058529 to J. R. L., and NHGRI 5U54HG003273 to R. A. G. T. H. is supported by the Medical Genetics Research Fellowship Program (T32 GM07526). W. W. is supported by Career Development Award K23NS078056 from NINDS. The authors would like to thank the ExAC and the groups that provided exome variant data for comparison. A full list of contributing groups can be found at http://exac.broadinstitute.org/about. J.R.L. has stock ownership in 23andMe and Lasergen and is a paid consultant for Regeneron. J. R. L. is also a coinventor on multiple United States and European patents related to molecular diagnostics for inherited neuropathies, eye diseases, and bacterial genomic fingerprinting. The Department of Molecular and Human Genetics at Baylor College of Medicine derives revenue from the chromosomal microarray analysis and clinical exome sequencing offered in the Medical Genetics Laboratory (https://www.bcm.edu/geneticlabs/). W. K. C. is a paid consultant for Regeneron and BioReference Laboratories. C.G.-J. and J. D. O. are employees of the RGC.
- Full Text
- View/download PDF
126. Expanding the clinical spectrum of biglycan-related Meester-Loeys syndrome.
- Author
-
Meester JAN, Hebert A, Bastiaansen M, Rabaut L, Bastianen J, Boeckx N, Ashcroft K, Atwal PS, Benichou A, Billon C, Blankensteijn JD, Brennan P, Bucks SA, Campbell IM, Conrad S, Curtis SL, Dasouki M, Dent CL, Eden J, Goel H, Hartill V, Houweling AC, Isidor B, Jackson N, Koopman P, Korpioja A, Kraatari-Tiri M, Kuulavainen L, Lee K, Low KJ, Lu AC, McManus ML, Oakley SP, Oliver J, Organ NM, Overwater E, Revencu N, Trainer AH, Trivedi B, Turner CLS, Whittington R, Zankl A, Zentner D, Van Laer L, Verstraeten A, and Loeys BL
- Abstract
Pathogenic loss-of-function variants in BGN, an X-linked gene encoding biglycan, are associated with Meester-Loeys syndrome (MRLS), a thoracic aortic aneurysm/dissection syndrome. Since the initial publication of five probands in 2017, we have considerably expanded our MRLS cohort to a total of 18 probands (16 males and 2 females). Segregation analyses identified 36 additional BGN variant-harboring family members (9 males and 27 females). The identified BGN variants were shown to lead to loss-of-function by cDNA and Western Blot analyses of skin fibroblasts or were strongly predicted to lead to loss-of-function based on the nature of the variant. No (likely) pathogenic missense variants without additional (predicted) splice effects were identified. Interestingly, a male proband with a deletion spanning the coding sequence of BGN and the 5' untranslated region of the downstream gene (ATP2B3) presented with a more severe skeletal phenotype. This may possibly be explained by expressional activation of the downstream ATPase ATP2B3 (normally repressed in skin fibroblasts) driven by the remnant BGN promotor. This study highlights that aneurysms and dissections in MRLS extend beyond the thoracic aorta, affecting the entire arterial tree, and cardiovascular symptoms may coincide with non-specific connective tissue features. Furthermore, the clinical presentation is more severe and penetrant in males compared to females. Extensive analysis at RNA, cDNA, and/or protein level is recommended to prove a loss-of-function effect before determining the pathogenicity of identified BGN missense and non-canonical splice variants. In conclusion, distinct mechanisms may underlie the wide phenotypic spectrum of MRLS patients carrying loss-of-function variants in BGN., (© 2024. The Author(s).)
- Published
- 2024
- Full Text
- View/download PDF
127. PhenoID, a language model normalizer of physical examinations from genetics clinical notes.
- Author
-
Weissenbacher D, Rawal S, Zhao X, Priestley JRC, Szigety KM, Schmidt SF, Higgins MJ, Magge A, O'Connor K, Gonzalez-Hernandez G, and Campbell IM
- Abstract
Background: Phenotypes identified during dysmorphology physical examinations are critical to genetic diagnosis and nearly universally documented as free-text in the electronic health record (EHR). Variation in how phenotypes are recorded in free-text makes large-scale computational analysis extremely challenging. Existing natural language processing (NLP) approaches to address phenotype extraction are trained largely on the biomedical literature or on case vignettes rather than actual EHR data., Methods: We implemented a tailored system at the Children's Hospital of Philadelpia that allows clinicians to document dysmorphology physical exam findings. From the underlying data, we manually annotated a corpus of 3136 organ system observations using the Human Phenotype Ontology (HPO). We provide this corpus publicly. We trained a transformer based NLP system to identify HPO terms from exam observations. The pipeline includes an extractor, which identifies tokens in the sentence expected to contain an HPO term, and a normalizer, which uses those tokens together with the original observation to determine the specific term mentioned., Findings: We find that our labeler and normalizer NLP pipeline, which we call PhenoID, achieves state-of-the-art performance for the dysmorphology physical exam phenotype extraction task. PhenoID's performance on the test set was 0.717, compared to the nearest baseline system (Pheno-Tagger) performance of 0.633. An analysis of our system's normalization errors shows possible imperfections in the HPO terminology itself but also reveals a lack of semantic understanding by our transformer models., Interpretation: Transformers-based NLP models are a promising approach to genetic phenotype extraction and, with recent development of larger pre-trained causal language models, may improve semantic understanding in the future. We believe our results also have direct applicability to more general extraction of medical signs and symptoms., Funding: US National Institutes of Health.
- Published
- 2024
- Full Text
- View/download PDF
128. Clinical decision support with a comprehensive in-EHR patient tracking system improves genetic testing follow up.
- Author
-
Campbell IM, Karavite DJ, Mcmanus ML, Cusick FC, Junod DC, Sheppard SE, Lourie EM, Shelov ED, Hakonarson H, Luberti AA, Muthu N, and Grundmeier RW
- Subjects
- Humans, Follow-Up Studies, Software, Genetic Testing, Electronic Health Records, Decision Support Systems, Clinical
- Abstract
Objective: We sought to develop and evaluate an electronic health record (EHR) genetic testing tracking system to address the barriers and limitations of existing spreadsheet-based workarounds., Materials and Methods: We evaluated the spreadsheet-based system using mixed effects logistic regression to identify factors associated with delayed follow up. These factors informed the design of an EHR-integrated genetic testing tracking system. After deployment, we assessed the system in 2 ways. We analyzed EHR access logs and note data to assess patient outcomes and performed semistructured interviews with users to identify impact of the system on work., Results: We found that patient-reported race was a significant predictor of documented genetic testing follow up, indicating a possible inequity in care. We implemented a CDS system including a patient data capture form and management dashboard to facilitate important care tasks. The system significantly sped review of results and significantly increased documentation of follow-up recommendations. Interviews with key system users identified a range of sociotechnical factors (ie, tools, tasks, collaboration) that contribute to safer and more efficient care., Discussion: Our new tracking system ended decades of workarounds for identifying and communicating test results and improved clinical workflows. Interview participants related that the system decreased cognitive and time burden which allowed them to focus on direct patient interaction., Conclusion: By assembling a multidisciplinary team, we designed a novel patient tracking system that improves genetic testing follow up. Similar approaches may be effective in other clinical settings., (© The Author(s) 2023. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
- Published
- 2023
- Full Text
- View/download PDF
129. Platelet findings in 22q11.2 deletion syndrome correlate with disease manifestations but do not correlate with GPIb surface expression.
- Author
-
Campbell IM, Crowley TB, Jobaliya C, Bailey A, McGinn DE, Gaiser K, Bassett A, Gur RE, Morrow B, Emanuel BS, Franco AT, French D, Zackai EH, McDonald-McGinn DM, and Lambert MP
- Subjects
- Humans, DiGeorge Syndrome genetics
- Abstract
Prior studies have demonstrated that patients with chromosome 22q11.2 deletion syndrome (22q11.2DS) have lower platelet counts (PC) compared to non-deleted populations. They also have an increased mean platelet volume. The mechanism for this has been postulated to be haploinsufficiency of the GPIBB gene. We examined platelet parameters, deletion size and factors known to influence counts, including status of thyroid hormone and congenital heart disease (CHD), in a population of 825 patients with 22q11.2DS. We also measured surface expression of GPIB-IX complex by flow cytometry. The major determinant of PC was deletion status of GP1BB, regardless of surface expression or other factors. Patients with nested distal chromosome 22q11.2 deletions (those with GP1BB present) had higher PCs than those with proximal deletions where GP1BB is deleted. Patients with 22q11.2DS also demonstrated an accelerated PC decrease with age, occurring in childhood. These data demonstrate that genes within the proximal deletion segment drive PC differences in 22q11.2DS and suggest that PC reference ranges may need to be adjusted for age and deletion size in 22q11.2DS populations. Bleeding did not correlate with either platelet count or GPIb expression. Further studies into drivers of expression of GPIb and associations with severe thrombocytopenia and immune thrombocytopenia are needed to inform clinical care., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
- Published
- 2023
- Full Text
- View/download PDF
130. The experience of one pediatric geneticist with telemedicine-based clinical diagnosis.
- Author
-
Campbell IM, Crowley TB, Keena B, Donoghue S, McManus ML, and Zackai EH
- Subjects
- Child, Humans, Pandemics, COVID-19 diagnosis, COVID-19 epidemiology, Telemedicine methods, Physicians
- Abstract
Telemedicine has long been considered as an attractive alternative methodology in clinical genetics to improve patient access and convenience. Given the importance of the dysmorphology physical examination and anthropometric measurement in clinical genetics, many have wondered if lost information would hamper diagnosis. We previously addressed this question by analyzing thousands of diagnostic encounters in a single practice involving multiple practitioners and found no evidence for a difference in new molecular diagnosis rates. However, our previous study design resulted in variability in providers between in-person and telemedicine evaluation groups. To address this in our present study, we expanded our analysis to 1104 new patient evaluations seen by one highly experienced clinical geneticist across two 10-month periods before and after the start of the COVID-19 pandemic. Comparing patients seen in-person to those seen by telemedicine, we found significant differences in race and ethnicity, preferred language, and home zip code median income. The clinical geneticist intended to send more genetic testing for those patients seen by telemedicine, but due to issues with test authorization and sample collection, there was no difference in ultimate completion rate between groups. We found no significant difference in new molecular diagnosis rate. Overall, we find telemedicine to be an acceptable alternative to in-person evaluation for routine pediatric clinical genetics care., (© 2022 Wiley Periodicals LLC.)
- Published
- 2022
- Full Text
- View/download PDF
131. Malate dehydrogenase 2 deficiency is an emerging cause of pediatric epileptic encephalopathy with a recognizable biochemical signature.
- Author
-
Priestley JRC, Pace LM, Sen K, Aggarwal A, Alves CAPF, Campbell IM, Cuddapah SR, Engelhardt NM, Eskandar M, Jolín García PC, Gropman A, Helbig I, Hong X, Gowda VK, Lusk L, Trapane P, Srinivasan VM, Suwannarat P, and Ganetzky RD
- Abstract
Malate dehydrogenases (MDH) serve a critical role in maintaining equilibrium of the NAD+/NADH ratio between the mitochondria and cytosol through the catalysis of the oxidation of L-malate to oxaloacetate in a reversible, NADH-dependent manner. MDH2 encodes the mitochondrial isoform, which is integral to the tricarboxylic acid cycle and thus energy homeostasis. Recently, five patients harboring compound heterozygous MDH2 variants have been described, three with early-onset epileptic encephalopathy, one with a stroke-like episode, and one with dilated cardiomyopathy. Here, we describe an additional seven patients with biallelic variants in MDH2 , the largest and most neurodevelopmentally and ethnically diverse cohort to-date, including homozygous variants, a sibling pair, non-European patients, and an adult. From these patients, we learn that MDH2 deficiency results in a biochemical signature including elevations of plasma lactate and the lactate:pyruvate ratio with urinary excretion of malate. It also results in a recognizable constellation of neuroimaging findings of anterior-predominant cerebral atrophy, subependymal cysts with ventricular septations. We also recognize MDH2 deficiency as a cause of Leigh syndrome. Taken with existing patient reports, we conclude that MDH2 deficiency is an emerging and likely under-recognized cause of infantile epileptic encephalopathy and provide a framework for medical evaluation of patients identified with biallelic MDH2 variants., Competing Interests: None to report., (© 2022 The Authors.)
- Published
- 2022
- Full Text
- View/download PDF
132. Identifying phenotypic expansions for congenital diaphragmatic hernia plus (CDH+) using DECIPHER data.
- Author
-
Hardcastle A, Berry AM, Campbell IM, Zhao X, Liu P, Gerard AE, Rosenfeld JA, Sisoudiya SD, Hernandez-Garcia A, Loddo S, Di Tommaso S, Novelli A, Dentici ML, Capolino R, Digilio MC, Graziani L, Rustad CF, Neas K, Ferrero GB, Brusco A, Di Gregorio E, Wellesley D, Beneteau C, Joubert M, Van Den Bogaert K, Boogaerts A, McMullan DJ, Dean J, Giuffrida MG, Bernardini L, Varghese V, Shannon NL, Harrison RE, Lam WWK, McKee S, Turnpenny PD, Cole T, Morton J, Eason J, Jones MC, Hall R, Wright M, Horridge K, Shaw CA, Chung WK, and Scott DA
- Subjects
- Animals, DNA Copy Number Variations, Diaphragm, Mice, Hernias, Diaphragmatic, Congenital genetics
- Abstract
Congenital diaphragmatic hernia (CDH) can occur in isolation or in conjunction with other birth defects (CDH+). A molecular etiology can only be identified in a subset of CDH cases. This is due, in part, to an incomplete understanding of the genes that contribute to diaphragm development. Here, we used clinical and molecular data from 36 individuals with CDH+ who are cataloged in the DECIPHER database to identify genes that may play a role in diaphragm development and to discover new phenotypic expansions. Among this group, we identified individuals who carried putatively deleterious sequence or copy number variants affecting CREBBP, SMARCA4, UBA2, and USP9X. The role of these genes in diaphragm development was supported by their expression in the developing mouse diaphragm, their similarity to known CDH genes using data from a previously published and validated machine learning algorithm, and/or the presence of CDH in other individuals with their associated genetic disorders. Our results demonstrate how data from DECIPHER, and other public databases, can be used to identify new phenotypic expansions and suggest that CREBBP, SMARCA4, UBA2, and USP9X play a role in diaphragm development., (© 2022 Wiley Periodicals LLC.)
- Published
- 2022
- Full Text
- View/download PDF
133. Clinical Effectiveness of Telemedicine-Based Pediatric Genetics Care.
- Author
-
Szigety KM, Crowley TB, Gaiser KB, Chen EY, Priestley JRC, Williams LS, Rangu SA, Wright CM, Adusumalli P, Ahrens-Nicklas RC, Calderon B, Cuddapah SR, Edmondson A, Ficicioglu C, Ganetzky R, Kalish JM, Krantz ID, McDonald-McGinn DM, Medne L, Muraresku C, Pyle LC, Zackai EH, Campbell IM, and Sheppard SE
- Subjects
- Child, Humans, Patient Satisfaction, Retrospective Studies, Surveys and Questionnaires, Treatment Outcome, Telemedicine methods
- Abstract
Background and Objectives: Telemedicine may increase access to medical genetics care. However, in the pediatric setting, how telemedicine may affect the diagnostic rate is unknown, partially because of the perceived importance of the dysmorphology physical examination. We studied the clinical effectiveness of telemedicine for patients with suspected or confirmed genetic conditions., Methods: We conducted a retrospective cohort study of outpatient encounters before and after the widespread implementation of telemedicine (N = 5854). Visit types, diagnoses, patient demographic characteristics, and laboratory data were acquired from the electronic health record. Patient satisfaction was assessed through survey responses. New molecular diagnosis was the primary end point., Results: Patients seen by telemedicine were more likely to report non-Hispanic White ancestry, prefer to speak English, live in zip codes with higher median incomes, and have commercial insurance (all P < .01). Genetic testing was recommended for more patients evaluated by telemedicine than in person (79.5% vs 70.9%; P < .001). Patients seen in person were more likely to have a sample collected, resulting in similar test completion rates (telemedicine, 51.2%; in person, 55.1%; P = .09). There was no significant difference in molecular diagnosis rate between visit modalities (telemedicine, 13.8%; in person, 12.4%; P = .40)., Conclusions: Telemedicine and traditional in-person evaluation resulted in similar molecular diagnosis rates. However, improved methodologies for remote sample collection may be required. This study reveals the feasibility of telemedicine in a large academic medical genetics practice and is applicable to other pediatric specialties with perceived importance of physical examination., (Copyright © 2022 by the American Academy of Pediatrics.)
- Published
- 2022
- Full Text
- View/download PDF
134. Distinct immune trajectories in patients with chromosome 22q11.2 deletion syndrome and immune-mediated diseases.
- Author
-
Crowley TB, Campbell IM, Liebling EJ, Lambert MP, Levitt Katz LE, Heimall J, Bailey A, McGinn DE, McDonald McGinn DM, and Sullivan KE
- Subjects
- Adolescent, Adult, CD4 Lymphocyte Count, Child, Child, Preschool, Female, Humans, Infant, Male, Phenotype, Young Adult, Autoimmune Diseases immunology, CD4-Positive T-Lymphocytes immunology, DiGeorge Syndrome immunology, Hypersensitivity, Immediate immunology
- Abstract
Background: Identification of biomarkers associated with immune-mediated diseases in 22q11.2 deletion syndrome is an evolving field., Objectives: We sought to use a carefully phenotyped cohort to study immune parameters associated with autoimmunity and atopy in 22q11.2 deletion syndrome to define biomarkers associated with immune-mediated disease in this syndrome., Methods: Chart review validated autoimmune disease and atopic condition diagnoses. Laboratory data were extracted for each subcohort and plotted according to age. A random-effects model was used to define statistical significance., Results: CD19, CD4, and CD4/45RA lymphocyte populations were not different from the general cohort for patients with atopic conditions. CD4/45RA T cells were significantly lower in the subjects with immune thrombocytopenia compared with the general cohort, and CD4 T-cell counts were lower in patients with autoimmune thyroid disease., Conclusions: The mechanisms of autoimmunity in cytopenias may be distinct from those of solid-organ autoimmunity in 22q11.2 deletion syndrome. This study identifies potential biomarkers for risk stratification among commonly obtained laboratory studies., (Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)
- Published
- 2022
- Full Text
- View/download PDF
135. Proposed criteria for nevoid basal cell carcinoma syndrome in children assessed using statistical optimization.
- Author
-
Gold NB, Campbell IM, Sheppard SE, and Tan WH
- Subjects
- Adolescent, Adult, Age of Onset, Aged, Bayes Theorem, Child, Child, Preschool, Clinical Decision-Making, Disease Management, Female, Humans, Infant, Infant, Newborn, Male, Middle Aged, Practice Guidelines as Topic, Retrospective Studies, Young Adult, Basal Cell Nevus Syndrome diagnosis, Basal Cell Nevus Syndrome epidemiology, Carcinoma, Basal Cell diagnosis, Carcinoma, Basal Cell epidemiology
- Abstract
Nevoid basal cell carcinoma syndrome (NBCCS) is a tumor predisposition condition, the cardinal features of which emerge in adolescence or adulthood. Using statistical optimization, this study proposes NBCCS criteria with improved sensitivity in children less than 18 years of age. Earlier detection may lead to improved surveillance and prevention of sequelae. A survey eliciting medical history was completed by, or on behalf of, individuals with NBCCS. Based on these findings, criteria for suspicion of NBCCS in children were suggested using information from a Bernoulli naïve Bayes classifier relying on the human phenotype ontology. The sensitivity and specificity of the existing and proposed diagnostic criteria were also assessed. Participants (n = 48) reported their first signs of NBCCS appeared at a median age of 8 months, but by our retrospective analysis, they did not fulfill the current diagnostic criteria until a median age of 7 years. This study delineates the early-onset features of NBCCS and proposes criteria that should prompt consideration of NBCCS. Additionally, we demonstrate a method for quantitatively assessing the utility of diagnostic criteria for genetic disorders., (© 2021. The Author(s).)
- Published
- 2021
- Full Text
- View/download PDF
136. Provider Perspectives on the Impact of the COVID-19 Pandemic on Newborn Screening.
- Author
-
Gold JI, Campbell IM, and Ficicioglu C
- Abstract
The onset of the COVID-19 pandemic caused significant changes in healthcare delivery. Telemedicine rapidly and unexpectedly became the primary vehicle for ambulatory management. As newborn screen (NBS) referrals require varying levels of acuity, whether telemedicine could be used as a safe and effective medium to return these results were unknown. We sent an online survey to metabolism providers internationally to investigate triage differences of abnormal NBS results during the COVID-19 pandemic. The survey compared personal practice for the periods of March-June 2019 and March-June 2020. Responses were received from 44 providers practicing in 8 countries. Nearly all (93%) practiced in areas of widespread SARS-COV-2 community transmission during spring 2020. There was a significant expansion of telemedicine use for NBS referrals at the onset of the COVID-19 pandemic (OR: 12, 95% CI: 3.66-39.3, p < 0.0001). Telehealth primarily replaced in-person ambulatory metabolism visits. The increased frequency of virtual care was similar across NBS analytes. Providers found telehealth for NBS referral equally efficacious to in-person care. Institutional patient surveys showed no difference in satisfaction with provider communication, provider empathy, or appointment logistics. Our survey was limited by unprecedented disruption in healthcare delivery, necessitating further validation of telegenetics for NBS in the post-pandemic era. Nevertheless, our findings demonstrate that telemedicine is potentially a viable and practical tool for triaging abnormal NBS results.
- Published
- 2021
- Full Text
- View/download PDF
137. Expanding the genotypic and phenotypic spectrum in a diverse cohort of 104 individuals with Wiedemann-Steiner syndrome.
- Author
-
Sheppard SE, Campbell IM, Harr MH, Gold N, Li D, Bjornsson HT, Cohen JS, Fahrner JA, Fatemi A, Harris JR, Nowak C, Stevens CA, Grand K, Au M, Graham JM Jr, Sanchez-Lara PA, Campo MD, Jones MC, Abdul-Rahman O, Alkuraya FS, Bassetti JA, Bergstrom K, Bhoj E, Dugan S, Kaplan JD, Derar N, Gripp KW, Hauser N, Innes AM, Keena B, Kodra N, Miller R, Nelson B, Nowaczyk MJ, Rahbeeni Z, Ben-Shachar S, Shieh JT, Slavotinek A, Sobering AK, Abbott MA, Allain DC, Amlie-Wolf L, Au PYB, Bedoukian E, Beek G, Barry J, Berg J, Bernstein JA, Cytrynbaum C, Chung BH, Donoghue S, Dorrani N, Eaton A, Flores-Daboub JA, Dubbs H, Felix CA, Fong CT, Fung JLF, Gangaram B, Goldstein A, Greenberg R, Ha TK, Hersh J, Izumi K, Kallish S, Kravets E, Kwok PY, Jobling RK, Knight Johnson AE, Kushner J, Lee BH, Levin B, Lindstrom K, Manickam K, Mardach R, McCormick E, McLeod DR, Mentch FD, Minks K, Muraresku C, Nelson SF, Porazzi P, Pichurin PN, Powell-Hamilton NN, Powis Z, Ritter A, Rogers C, Rohena L, Ronspies C, Schroeder A, Stark Z, Starr L, Stoler J, Suwannarat P, Velinov M, Weksberg R, Wilnai Y, Zadeh N, Zand DJ, Falk MJ, Hakonarson H, Zackai EH, and Quintero-Rivera F
- Subjects
- Black People genetics, Constipation epidemiology, Constipation genetics, Constipation pathology, Failure to Thrive epidemiology, Failure to Thrive genetics, Failure to Thrive pathology, Genetic Association Studies, Growth Disorders epidemiology, Growth Disorders pathology, Humans, Hypertrichosis epidemiology, Hypertrichosis genetics, Hypertrichosis pathology, Intellectual Disability epidemiology, Intellectual Disability pathology, Loss of Function Mutation genetics, Retrospective Studies, White People genetics, Genetic Predisposition to Disease, Growth Disorders genetics, Histone-Lysine N-Methyltransferase genetics, Hypertrichosis congenital, Intellectual Disability genetics, Myeloid-Lymphoid Leukemia Protein genetics
- Abstract
Wiedemann-Steiner syndrome (WSS) is an autosomal dominant disorder caused by monoallelic variants in KMT2A and characterized by intellectual disability and hypertrichosis. We performed a retrospective, multicenter, observational study of 104 individuals with WSS from five continents to characterize the clinical and molecular spectrum of WSS in diverse populations, to identify physical features that may be more prevalent in White versus Black Indigenous People of Color individuals, to delineate genotype-phenotype correlations, to define developmental milestones, to describe the syndrome through adulthood, and to examine clinicians' differential diagnoses. Sixty-nine of the 82 variants (84%) observed in the study were not previously reported in the literature. Common clinical features identified in the cohort included: developmental delay or intellectual disability (97%), constipation (63.8%), failure to thrive (67.7%), feeding difficulties (66.3%), hypertrichosis cubiti (57%), short stature (57.8%), and vertebral anomalies (46.9%). The median ages at walking and first words were 20 months and 18 months, respectively. Hypotonia was associated with loss of function (LoF) variants, and seizures were associated with non-LoF variants. This study identifies genotype-phenotype correlations as well as race-facial feature associations in an ethnically diverse cohort, and accurately defines developmental trajectories, medical comorbidities, and long-term outcomes in individuals with WSS., (© 2021 Wiley Periodicals LLC.)
- Published
- 2021
- Full Text
- View/download PDF
138. Predicting human genes susceptible to genomic instability associated with Alu / Alu -mediated rearrangements.
- Author
-
Song X, Beck CR, Du R, Campbell IM, Coban-Akdemir Z, Gu S, Breman AM, Stankiewicz P, Ira G, Shaw CA, and Lupski JR
- Subjects
- Gene Duplication genetics, Genome, Human genetics, Humans, Sequence Deletion, Alu Elements genetics, DNA Copy Number Variations genetics, Genomic Instability genetics
- Abstract
Alu elements, the short interspersed element numbering more than 1 million copies per human genome, can mediate the formation of copy number variants (CNVs) between substrate pairs. These Alu / Alu -mediated rearrangements (AAMRs) can result in pathogenic variants that cause diseases. To investigate the impact of AAMR on gene variation and human health, we first characterized Alu s that are involved in mediating CNVs (CNV- Alu s) and observed that these Alu s tend to be evolutionarily younger. We then computationally generated, with the assistance of a supercomputer, a test data set consisting of 78 million Alu pairs and predicted ∼18% of them are potentially susceptible to AAMR. We further determined the relative risk of AAMR in 12,074 OMIM genes using the count of predicted CNV- Alu pairs and experimentally validated the predictions with 89 samples selected by correlating predicted hotspots with a database of CNVs identified by clinical chromosomal microarrays (CMAs) on the genomes of approximately 54,000 subjects. We fine-mapped 47 duplications, 40 deletions, and two complex rearrangements and examined a total of 52 breakpoint junctions of simple CNVs. Overall, 94% of the candidate breakpoints were at least partially Alu mediated. We successfully predicted all (100%) of Alu pairs that mediated deletions ( n = 21) and achieved an 87% positive predictive value overall when including AAMR-generated deletions and duplications. We provided a tool, AluAluCNVpredictor, for assessing AAMR hotspots and their role in human disease. These results demonstrate the utility of our predictive model and provide insights into the genomic features and molecular mechanisms underlying AAMR., (© 2018 Song et al.; Published by Cold Spring Harbor Laboratory Press.)
- Published
- 2018
- Full Text
- View/download PDF
139. Multiallelic Positions in the Human Genome: Challenges for Genetic Analyses.
- Author
-
Campbell IM, Gambin T, Jhangiani S, Grove ML, Veeraraghavan N, Muzny DM, Shaw CA, Gibbs RA, Boerwinkle E, Yu F, and Lupski JR
- Subjects
- Humans, Alleles, Exome genetics, Genome, Human genetics
- Abstract
As the amount of human genomic sequence available from personal genomes and exomes has increased, so too has the observation of genomic positions having two or more alternative alleles, so-called multiallelic sites. For portions of the haploid genome that are present in more than one copy, including segmental duplications, variation at such multisite variant positions becomes even more complex. Despite the frequency of multiallelic variants, a number of commonly used resources and tools in genomic research and diagnostics do not support these multiallelic variants all together or require special modifications. Here, we explore the frequency of multiallelic sites in large samples with whole exome sequencing and discuss potential outcomes of failing to account for multiple variant alleles. We also briefly discuss some commonly utilized resources that fully support multiallelic sites., (© 2015 WILEY PERIODICALS, INC.)
- Published
- 2016
- Full Text
- View/download PDF
140. DNA REPAIR. Mus81 and converging forks limit the mutagenicity of replication fork breakage.
- Author
-
Mayle R, Campbell IM, Beck CR, Yu Y, Wilson M, Shaw CA, Bjergbaek L, Lupski JR, and Ira G
- Subjects
- Alu Elements, Base Sequence, DNA-Binding Proteins genetics, DNA-Directed DNA Polymerase metabolism, Endonucleases genetics, Humans, Molecular Sequence Data, Neoplasms genetics, Saccharomyces cerevisiae genetics, Saccharomyces cerevisiae Proteins genetics, DNA Breaks, Double-Stranded, DNA Repair genetics, DNA Replication genetics, DNA-Binding Proteins metabolism, Endonucleases metabolism, Genomic Instability, Saccharomyces cerevisiae Proteins metabolism
- Abstract
Most spontaneous DNA double-strand breaks (DSBs) result from replication-fork breakage. Break-induced replication (BIR), a genome rearrangement-prone repair mechanism that requires the Pol32/POLD3 subunit of eukaryotic DNA Polδ, was proposed to repair broken forks, but how genome destabilization is avoided was unknown. We show that broken fork repair initially uses error-prone Pol32-dependent synthesis, but that mutagenic synthesis is limited to within a few kilobases from the break by Mus81 endonuclease and a converging fork. Mus81 suppresses template switches between both homologous sequences and diverged human Alu repetitive elements, highlighting its importance for stability of highly repetitive genomes. We propose that lack of a timely converging fork or Mus81 may propel genome instability observed in cancer., (Copyright © 2015, American Association for the Advancement of Science.)
- Published
- 2015
- Full Text
- View/download PDF
141. Alu-mediated diverse and complex pathogenic copy-number variants within human chromosome 17 at p13.3.
- Author
-
Gu S, Yuan B, Campbell IM, Beck CR, Carvalho CM, Nagamani SC, Erez A, Patel A, Bacino CA, Shaw CA, Stankiewicz P, Cheung SW, Bi W, and Lupski JR
- Subjects
- Alleles, Base Sequence, Comparative Genomic Hybridization, Female, Gene Duplication, Gene Rearrangement, Genome, Human, Genomic Instability, Genomics, Homologous Recombination, Humans, Male, Molecular Sequence Data, Segmental Duplications, Genomic, Sequence Deletion, Alu Elements genetics, Chromosomes, Human, Pair 17 genetics, DNA Copy Number Variations
- Abstract
Alu repetitive elements are known to be major contributors to genome instability by generating Alu-mediated copy-number variants (CNVs). Most of the reported Alu-mediated CNVs are simple deletions and duplications, and the mechanism underlying Alu-Alu-mediated rearrangement has been attributed to non-allelic homologous recombination (NAHR). Chromosome 17 at the p13.3 genomic region lacks extensive low-copy repeat architecture; however, it is highly enriched for Alu repetitive elements, with a fraction of 30% of total sequence annotated in the human reference genome, compared with the 10% genome-wide and 18% on chromosome 17. We conducted mechanistic studies of the 17p13.3 CNVs by performing high-density oligonucleotide array comparative genomic hybridization, specifically interrogating the 17p13.3 region with ∼150 bp per probe density; CNV breakpoint junctions were mapped to nucleotide resolution by polymerase chain reaction and Sanger sequencing. Studied rearrangements include 5 interstitial deletions, 14 tandem duplications, 7 terminal deletions and 13 complex genomic rearrangements (CGRs). Within the 17p13.3 region, Alu-Alu-mediated rearrangements were identified in 80% of the interstitial deletions, 46% of the tandem duplications and 50% of the CGRs, indicating that this mechanism was a major contributor for formation of breakpoint junctions. Our studies suggest that Alu repetitive elements facilitate formation of non-recurrent CNVs, CGRs and other structural aberrations of chromosome 17 at p13.3. The common observation of Alu-mediated rearrangement in CGRs and breakpoint junction sequences analysis further demonstrates that this type of mechanism is unlikely attributed to NAHR, but rather may be due to a recombination-coupled DNA replicative repair process., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)
- Published
- 2015
- Full Text
- View/download PDF
142. Genome-wide analyses of LINE-LINE-mediated nonallelic homologous recombination.
- Author
-
Startek M, Szafranski P, Gambin T, Campbell IM, Hixson P, Shaw CA, Stankiewicz P, and Gambin A
- Subjects
- Algorithms, Chromosome Breakpoints, Comparative Genomic Hybridization, DNA Copy Number Variations, Genomics methods, Humans, Polymerase Chain Reaction, Genome, Human, Homologous Recombination, Long Interspersed Nucleotide Elements
- Abstract
Nonallelic homologous recombination (NAHR), occurring between low-copy repeats (LCRs) >10 kb in size and sharing >97% DNA sequence identity, is responsible for the majority of recurrent genomic rearrangements in the human genome. Recent studies have shown that transposable elements (TEs) can also mediate recurrent deletions and translocations, indicating the features of substrates that mediate NAHR may be significantly less stringent than previously believed. Using >4 kb length and >95% sequence identity criteria, we analyzed of the genome-wide distribution of long interspersed element (LINE) retrotransposon and their potential to mediate NAHR. We identified 17 005 directly oriented LINE pairs located <10 Mbp from each other as potential NAHR substrates, placing 82.8% of the human genome at risk of LINE-LINE-mediated instability. Cross-referencing these regions with CNVs in the Baylor College of Medicine clinical chromosomal microarray database of 36 285 patients, we identified 516 CNVs potentially mediated by LINEs. Using long-range PCR of five different genomic regions in a total of 44 patients, we confirmed that the CNV breakpoints in each patient map within the LINE elements. To additionally assess the scale of LINE-LINE/NAHR phenomenon in the human genome, we tested DNA samples from six healthy individuals on a custom aCGH microarray targeting LINE elements predicted to mediate CNVs and identified 25 LINE-LINE rearrangements. Our data indicate that LINE-LINE-mediated NAHR is widespread and under-recognized, and is an important mechanism of structural rearrangement contributing to human genomic variability., (© The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.)
- Published
- 2015
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.