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26 results on '"Whelan, Christopher W"'

1. Systematic evaluation of genome sequencing for the diagnostic assessment of autism spectrum disorder and fetal structural anomalies

Author

Lowther, Chelsea, Valkanas, Elise, Giordano, Jessica L., Wang, Harold Z., Currall, Benjamin B., O’Keefe, Kathryn, Pierce-Hoffman, Emma, Kurtas, Nehir E., Whelan, Christopher W., Hao, Stephanie P., Weisburd, Ben, Jalili, Vahid, Fu, Jack, Wong, Isaac, Collins, Ryan L., Zhao, Xuefang, Austin-Tse, Christina A., Evangelista, Emily, Lemire, Gabrielle, Aggarwal, Vimla S., Lucente, Diane, Gauthier, Laura D., Tolonen, Charlotte, Sahakian, Nareh, Stevens, Christine, An, Joon-Yong, Dong, Shan, Norton, Mary E., MacKenzie, Tippi C., Devlin, Bernie, Gilmore, Kelly, Powell, Bradford C., Brandt, Alicia, Vetrini, Francesco, DiVito, Michelle, Sanders, Stephan J., MacArthur, Daniel G., Hodge, Jennelle C., O'Donnell-Luria, Anne, Rehm, Heidi L., Vora, Neeta L., Levy, Brynn, Brand, Harrison, Wapner, Ronald J., and Talkowski, Michael E.

Published
2023
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2. Complement genes contribute sex-biased vulnerability in diverse disorders.

Author

Kamitaki, Nolan, Sekar, Aswin, Handsaker, Robert E, de Rivera, Heather, Tooley, Katherine, Morris, David L, Taylor, Kimberly E, Whelan, Christopher W, Tombleson, Philip, Loohuis, Loes M Olde, Schizophrenia Working Group of the Psychiatric Genomics Consortium, Boehnke, Michael, Kimberly, Robert P, Kaufman, Kenneth M, Harley, John B, Langefeld, Carl D, Seidman, Christine E, Pato, Michele T, Pato, Carlos N, Ophoff, Roel A, Graham, Robert R, Criswell, Lindsey A, Vyse, Timothy J, and McCarroll, Steven A

Subjects
Schizophrenia Working Group of the Psychiatric Genomics Consortium, Humans, Sjogren's Syndrome, Lupus Erythematosus, Systemic, Genetic Predisposition to Disease, HLA Antigens, Major Histocompatibility Complex, Sex Characteristics, Haplotypes, Alleles, Adult, Middle Aged, Complement C3, Complement C4, Female, Male, Young Adult, Lupus, Brain Disorders, Schizophrenia, Biotechnology, Genetics, Mental Health, Autoimmune Disease, 2.1 Biological and endogenous factors, Inflammatory and immune system, General Science & Technology
Abstract

Many common illnesses, for reasons that have not been identified, differentially affect men and women. For instance, the autoimmune diseases systemic lupus erythematosus (SLE) and Sjögren's syndrome affect nine times more women than men1, whereas schizophrenia affects men with greater frequency and severity relative to women2. All three illnesses have their strongest common genetic associations in the major histocompatibility complex (MHC) locus, an association that in SLE and Sjögren's syndrome has long been thought to arise from alleles of the human leukocyte antigen (HLA) genes at that locus3-6. Here we show that variation of the complement component 4 (C4) genes C4A and C4B, which are also at the MHC locus and have been linked to increased risk for schizophrenia7, generates 7-fold variation in risk for SLE and 16-fold variation in risk for Sjögren's syndrome among individuals with common C4 genotypes, with C4A protecting more strongly than C4B in both illnesses. The same alleles that increase risk for schizophrenia greatly reduce risk for SLE and Sjögren's syndrome. In all three illnesses, C4 alleles act more strongly in men than in women: common combinations of C4A and C4B generated 14-fold variation in risk for SLE, 31-fold variation in risk for Sjögren's syndrome, and 1.7-fold variation in schizophrenia risk among men (versus 6-fold, 15-fold and 1.26-fold variation in risk among women, respectively). At a protein level, both C4 and its effector C3 were present at higher levels in cerebrospinal fluid and plasma8,9 in men than in women among adults aged between 20 and 50 years, corresponding to the ages of differential disease vulnerability. Sex differences in complement protein levels may help to explain the more potent effects of C4 alleles in men, women's greater risk of SLE and Sjögren's syndrome and men's greater vulnerability to schizophrenia. These results implicate the complement system as a source of sexual dimorphism in vulnerability to diverse illnesses.

Published
2020

3. A structural variation reference for medical and population genetics

Author

Collins, Ryan L, Brand, Harrison, Karczewski, Konrad J, Zhao, Xuefang, Alföldi, Jessica, Francioli, Laurent C, Khera, Amit V, Lowther, Chelsea, Gauthier, Laura D, Wang, Harold, Watts, Nicholas A, Solomonson, Matthew, O’Donnell-Luria, Anne, Baumann, Alexander, Munshi, Ruchi, Walker, Mark, Whelan, Christopher W, Huang, Yongqing, Brookings, Ted, Sharpe, Ted, Stone, Matthew R, Valkanas, Elise, Fu, Jack, Tiao, Grace, Laricchia, Kristen M, Ruano-Rubio, Valentin, Stevens, Christine, Gupta, Namrata, Cusick, Caroline, Margolin, Lauren, Taylor, Kent D, Lin, Henry J, Rich, Stephen S, Post, Wendy S, Chen, Yii-Der Ida, Rotter, Jerome I, Nusbaum, Chad, Philippakis, Anthony, Lander, Eric, Gabriel, Stacey, Neale, Benjamin M, Kathiresan, Sekar, Daly, Mark J, Banks, Eric, MacArthur, Daniel G, and Talkowski, Michael E

Subjects
Biological Sciences, Bioinformatics and Computational Biology, Genetics, Biotechnology, Human Genome, Generic health relevance, Disease, Female, Genetic Testing, Genetic Variation, Genetics, Medical, Genetics, Population, Genome, Human, Genotyping Techniques, Humans, Male, Middle Aged, Mutation, Polymorphism, Single Nucleotide, Racial Groups, Reference Standards, Selection, Genetic, Whole Genome Sequencing, Genome Aggregation Database Production Team, Genome Aggregation Database Consortium, General Science & Technology
Abstract

Structural variants (SVs) rearrange large segments of DNA1 and can have profound consequences in evolution and human disease2,3. As national biobanks, disease-association studies, and clinical genetic testing have grown increasingly reliant on genome sequencing, population references such as the Genome Aggregation Database (gnomAD)4 have become integral in the interpretation of single-nucleotide variants (SNVs)5. However, there are no reference maps of SVs from high-coverage genome sequencing comparable to those for SNVs. Here we present a reference of sequence-resolved SVs constructed from 14,891 genomes across diverse global populations (54% non-European) in gnomAD. We discovered a rich and complex landscape of 433,371 SVs, from which we estimate that SVs are responsible for 25-29% of all rare protein-truncating events per genome. We found strong correlations between natural selection against damaging SNVs and rare SVs that disrupt or duplicate protein-coding sequence, which suggests that genes that are highly intolerant to loss-of-function are also sensitive to increased dosage6. We also uncovered modest selection against noncoding SVs in cis-regulatory elements, although selection against protein-truncating SVs was stronger than all noncoding effects. Finally, we identified very large (over one megabase), rare SVs in 3.9% of samples, and estimate that 0.13% of individuals may carry an SV that meets the existing criteria for clinically important incidental findings7. This SV resource is freely distributed via the gnomAD browser8 and will have broad utility in population genetics, disease-association studies, and diagnostic screening.

Published
2020

4. A whole-genome sequence study identifies genetic risk factors for neuromyelitis optica.

Author

Estrada, Karol, Whelan, Christopher W, Zhao, Fengmei, Bronson, Paola, Handsaker, Robert E, Sun, Chao, Carulli, John P, Harris, Tim, Ransohoff, Richard M, McCarroll, Steven A, Day-Williams, Aaron G, Greenberg, Benjamin M, and MacArthur, Daniel G

Subjects
Humans, Neuromyelitis Optica, Genetic Predisposition to Disease, Immunoglobulin G, Risk Factors, Major Histocompatibility Complex, Haplotypes, Polymorphism, Single Nucleotide, Adult, Middle Aged, Female, Male, Aquaporin 4, DNA Copy Number Variations, Whole Genome Sequencing, Polymorphism, Single Nucleotide
Abstract

Neuromyelitis optica (NMO) is a rare autoimmune disease that affects the optic nerve and spinal cord. Most NMO patients ( > 70%) are seropositive for circulating autoantibodies against aquaporin 4 (NMO-IgG+). Here, we meta-analyze whole-genome sequences from 86 NMO cases and 460 controls with genome-wide SNP array from 129 NMO cases and 784 controls to test for association with SNPs and copy number variation (total N = 215 NMO cases, 1244 controls). We identify two independent signals in the major histocompatibility complex (MHC) region associated with NMO-IgG+, one of which may be explained by structural variation in the complement component 4 genes. Mendelian Randomization analysis reveals a significant causal effect of known systemic lupus erythematosus (SLE), but not multiple sclerosis (MS), risk variants in NMO-IgG+. Our results suggest that genetic variants in the MHC region contribute to the etiology of NMO-IgG+ and that NMO-IgG+ is genetically more similar to SLE than MS.

Published
2018

6. Rare germline structural variants increase risk for pediatric solid tumors

Author

Gillani, Riaz, primary, Collins, Ryan L, additional, Crowdis, Jett, additional, Garza, Amanda, additional, Jones, Jill K, additional, Walker, Mark, additional, Sanchis-Juan, Alba, additional, Whelan, Christopher W., additional, Pierce-Hoffman, Emma, additional, Talkowski, Michael E, additional, Brand, Harrison, additional, Haigis, Kevin M, additional, LoPiccolo, Jaclyn, additional, AlDubayan, Saud H., additional, Gusev, Alexander H., additional, Crompton, Brian D, additional, Janeway, Katherine, additional, and Van Allen, Eliezer, additional

Published
2024
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8. Cloudbreak: Accurate and Scalable Genomic Structural Variation Detection in the Cloud with MapReduce

Author

Whelan, Christopher W., Tyner, Jeffrey, L'Abbate, Alberto, Storlazzi, Clelia Tiziana, Carbone, Lucia, and Sönmez, Kemal

Subjects
Quantitative Biology - Genomics
Abstract

The detection of genomic structural variations (SV) remains a difficult challenge in analyzing sequencing data, and the growing size and number of sequenced genomes have rendered SV detection a bona fide big data problem. MapReduce is a proven, scalable solution for distributed computing on huge data sets. We describe a conceptual framework for SV detection algorithms in MapReduce based on computing local genomic features, and use it to develop a deletion and insertion detection algorithm, Cloudbreak. On simulated and real data sets, Cloudbreak achieves accuracy improvements over popular SV detection algorithms, and genotypes variants from diploid samples. It provides dramatically shorter runtimes and the ability to scale to big data volumes on large compute clusters. Cloudbreak includes tools to set up and configure MapReduce (Hadoop) clusters on cloud services, enabling on-demand cluster computing. Our implementation and source code are available at http://github.com/cwhelan/cloudbreak ., Comment: 16 Pages main paper, 3 main figures, 2 main tables; 27 pages supplementary material including 13 page user manual, 5 supplementary figures. Code available at http://github.com/cwhelan/cloudbreak . Update: removed trailing period in abstract URL that was breaking link to GitHub; fixed colors in main figures

Published
2013

9. High-Resolution and Noninvasive Fetal Exome Screening

Author

Brand, Harrison, primary, Whelan, Christopher W., additional, Duyzend, Michael, additional, Lemanski, John, additional, Salani, Monica, additional, Hao, Stephanie P., additional, Wong, Isaac, additional, Valkanas, Elise, additional, Cusick, Caroline, additional, Genetti, Casie, additional, Dobson, Lori, additional, Studwell, Courtney, additional, Gianforcaro, Kathleen, additional, Wilkins-Haug, Louise, additional, Guseh, Stephanie, additional, Currall, Benjamin, additional, Gray, Kathryn, additional, and Talkowski, Michael E., additional

Published
2023
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10. Structural Alterations Driving Castration-Resistant Prostate Cancer Revealed by Linked-Read Genome Sequencing

Author

Viswanathan, Srinivas R., Ha, Gavin, Hoff, Andreas M., Wala, Jeremiah A., Carrot-Zhang, Jian, Whelan, Christopher W., Haradhvala, Nicholas J., Freeman, Samuel S., Reed, Sarah C., Rhoades, Justin, Polak, Paz, Cipicchio, Michelle, Wankowicz, Stephanie A., Wong, Alicia, Kamath, Tushar, Zhang, Zhenwei, Gydush, Gregory J., Rotem, Denisse, Love, J. Christopher, Getz, Gad, Gabriel, Stacey, Zhang, Cheng-Zhong, Dehm, Scott M., Nelson, Peter S., Van Allen, Eliezer M., Choudhury, Atish D., Adalsteinsson, Viktor A., Beroukhim, Rameen, Taplin, Mary-Ellen, Meyerson, Matthew, Viswanathan, Srinivas R., Ha, Gavin, Hoff, Andreas M., Wala, Jeremiah A., Carrot-Zhang, Jian, Whelan, Christopher W., Haradhvala, Nicholas J., Freeman, Samuel S., Reed, Sarah C., Rhoades, Justin, Polak, Paz, Cipicchio, Michelle, Wankowicz, Stephanie A., Wong, Alicia, Kamath, Tushar, Zhang, Zhenwei, Gydush, Gregory J., Rotem, Denisse, Love, J. Christopher, Getz, Gad, Gabriel, Stacey, Zhang, Cheng-Zhong, Dehm, Scott M., Nelson, Peter S., Van Allen, Eliezer M., Choudhury, Atish D., Adalsteinsson, Viktor A., Beroukhim, Rameen, Taplin, Mary-Ellen, and Meyerson, Matthew

Abstract

© 2018 Elsevier Inc. Nearly all prostate cancer deaths are from metastatic castration-resistant prostate cancer (mCRPC), but there have been few whole-genome sequencing (WGS) studies of this disease state. We performed linked-read WGS on 23 mCRPC biopsy specimens and analyzed cell-free DNA sequencing data from 86 patients with mCRPC. In addition to frequent rearrangements affecting known prostate cancer genes, we observed complex rearrangements of the AR locus in most cases. Unexpectedly, these rearrangements include highly recurrent tandem duplications involving an upstream enhancer of AR in 70%–87% of cases compared with <2% of primary prostate cancers. A subset of cases displayed AR or MYC enhancer duplication in the context of a genome-wide tandem duplicator phenotype associated with CDK12 inactivation. Our findings highlight the complex genomic structure of mCRPC, nominate alterations that may inform prostate cancer treatment, and suggest that additional recurrent events in the non-coding mCRPC genome remain to be discovered. Linked-read genome sequencing data from patients highlight that amplification of an enhancer upstream of the androgen receptor locus is a key feature of metastatic castration-resistant prostate cancer.

Published
2022

11. Gibbon genome and the fast karyotype evolution of small apes

Author

Carbone, Lucia, Alan Harris, R., Gnerre, Sante, Veeramah, Krishna R., Lorente-Galdos, Belen, Huddleston, John, Meyer, Thomas J., Herrero, Javier, Roos, Christian, Aken, Bronwen, Anaclerio, Fabio, Archidiacono, Nicoletta, Baker, Carl, Barrell, Daniel, Batzer, Mark A., Beal, Kathryn, Blancher, Antoine, Bohrson, Craig L., Brameier, Markus, Campbell, Michael S., Capozzi, Oronzo, Casola, Claudio, Chiatante, Giorgia, Cree, Andrew, Damert, Annette, de Jong, Pieter J., Dumas, Laura, Fernandez-Callejo, Marcos, Flicek, Paul, Fuchs, Nina V., Gut, Ivo, Gut, Marta, Hahn, Matthew W., Hernandez-Rodriguez, Jessica, Hillier, LaDeana W., Hubley, Robert, Ianc, Bianca, Izsvák, Zsuzsanna, Jablonski, Nina G., Johnstone, Laurel M., Karimpour-Fard, Anis, Konkel, Miriam K., Kostka, Dennis, Lazar, Nathan H., Lee, Sandra L., Lewis, Lora R., Liu, Yue, Locke, Devin P., Mallick, Swapan, Mendez, Fernando L., Muffato, Matthieu, Nazareth, Lynne V., Nevonen, Kimberly A., O’Bleness, Majesta, Ochis, Cornelia, Odom, Duncan T., Pollard, Katherine S., Quilez, Javier, Reich, David, Rocchi, Mariano, Schumann, Gerald G., Searle, Stephen, Sikela, James M., Skollar, Gabriella, Smit, Arian, Sonmez, Kemal, Hallers, Boudewijn ten, Terhune, Elizabeth, Thomas, Gregg W. C., Ullmer, Brygg, Ventura, Mario, Walker, Jerilyn A., Wall, Jeffrey D., Walter, Lutz, Ward, Michelle C., Wheelan, Sarah J., Whelan, Christopher W., White, Simon, Wilhelm, Larry J., Woerner, August E., Yandell, Mark, Zhu, Baoli, Hammer, Michael F., Marques-Bonet, Tomas, Eichler, Evan E., Fulton, Lucinda, Fronick, Catrina, Muzny, Donna M., Warren, Wesley C., Worley, Kim C., Rogers, Jeffrey, Wilson, Richard K., and Gibbs, Richard A.

Published
2014
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12. Genomic organization and evolution of double minutes/homogeneously staining regions with MYC amplification in human cancer

Author

LʼAbbate, Alberto, Macchia, Gemma, DʼAddabbo, Pietro, Lonoce, Angelo, Tolomeo, Doron, Trombetta, Domenico, Kok, Klaas, Bartenhagen, Christoph, Whelan, Christopher W., Palumbo, Orazio, Severgnini, Marco, Cifola, Ingrid, Dugas, Martin, Carella, Massimo, De Bellis, Gianluca, Rocchi, Mariano, Carbone, Lucia, and Storlazzi, Clelia Tiziana

Published
2014
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14. Systematic evaluation of genome sequencing for the assessment of fetal structural anomalies

Author

Lowther, Chelsea, primary, Valkanas, Elise, additional, Giordano, Jessica L., additional, Wang, Harold Z., additional, Currall, Benjamin B., additional, O’Keefe, Kathryn, additional, Pierce-Hoffman, Emma, additional, Kurtas, Nehir E., additional, Whelan, Christopher W., additional, Hao, Stephanie P., additional, Weisburd, Ben, additional, Jalili, Vahid, additional, Fu, Jack, additional, Wong, Isaac, additional, Collins, Ryan L., additional, Zhao, Xuefang, additional, Austin-Tse, Christina A., additional, Evangelista, Emily, additional, Lemire, Gabrielle, additional, Aggarwal, Vimla S., additional, Lucente, Diane, additional, Gauthier, Laura D., additional, Tolonen, Charlotte, additional, Sahakian, Nareh, additional, Stevens, Christine, additional, An, Joon-Yong, additional, Dong, Shan, additional, Norton, Mary E., additional, MacKenzie, Tippi, additional, Devlin, Bernie, additional, Gilmore, Kelly, additional, Powell, Bradford C., additional, Brandt, Alicia, additional, Vetrini, Francesco, additional, DiVito, Michelle, additional, Sanders, Stephan J., additional, MacArthur, Daniel G., additional, Hodge, Jennelle C., additional, O’Donnell-Luria, Anne, additional, Rehm, Heidi L., additional, Vora, Neeta L., additional, Levy, Brynn, additional, Brand, Harrison, additional, Wapner, Ronald J., additional, and Talkowski, Michael E., additional

Published
2020
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17. Structural Alterations Driving Castration-Resistant Prostate Cancer Revealed by Linked-Read Genome Sequencing

Author

Viswanathan, Srinivas R., primary, Ha, Gavin, additional, Hoff, Andreas M., additional, Wala, Jeremiah A., additional, Carrot-Zhang, Jian, additional, Whelan, Christopher W., additional, Haradhvala, Nicholas J., additional, Freeman, Samuel S., additional, Reed, Sarah C., additional, Rhoades, Justin, additional, Polak, Paz, additional, Cipicchio, Michelle, additional, Wankowicz, Stephanie A., additional, Wong, Alicia, additional, Kamath, Tushar, additional, Zhang, Zhenwei, additional, Gydush, Gregory J., additional, Rotem, Denisse, additional, Love, J. Christopher, additional, Getz, Gad, additional, Gabriel, Stacey, additional, Zhang, Cheng-Zhong, additional, Dehm, Scott M., additional, Nelson, Peter S., additional, Van Allen, Eliezer M., additional, Choudhury, Atish D., additional, Adalsteinsson, Viktor A., additional, Beroukhim, Rameen, additional, Taplin, Mary-Ellen, additional, and Meyerson, Matthew, additional

Published
2018
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18. Ring chromosomes, breakpoint clusters, and neocentromeres in sarcomas

Author

Macchia, Gemma, Nord, Karolin H., D'Addabbo, Pietro, Whelan, Christopher W., Carbone, Lucia, Mertens, Fredrik, Rocchi, Mariano, Storlazzi, Clelia Tiziana, ZOLI, MONICA, PURGATO, STEFANIA, PERINI, GIOVANNI, Macchia, Gemma, Nord, Karolin H., Zoli, Monica, Purgato, Stefania, D'Addabbo, Pietro, Whelan, Christopher W., Carbone, Lucia, Perini, Giovanni, Mertens, Fredrik, Rocchi, Mariano, and Storlazzi, Clelia Tiziana

Subjects
Ring Chromosome, Cancer Research, Medicine (all), Centromere, Gene Amplification, Sarcoma, Epigenesis, Genetic, Chromosome Breakpoints, Chromosome Breakpoint, Genetic, Humans, Ring Chromosomes, In Situ Hybridization, Fluorescence, Human
Abstract

Gene amplification is relatively common in tumors. In certain subtypes of sarcoma, it often occurs in the form of ring and/or giant rod-shaped marker (RGM) chromosomes whose mitotic stability is frequently rescued by ectopic novel centromeres (neocentromeres). Little is known about the origin and structure of these RGM chromosomes, including how they arise, their internal organization, and which sequences underlie the neocentromeres. To address these questions, 42 sarcomas with RGM chromosomes were investigated to detect regions prone to double strand breaks and possible functional or structural constraints driving the amplification process. We found nine breakpoint cluster regions potentially involved in the genesis of RGM chromosomes, which turned out to be significantly enriched in poly-pyrimidine traits. Some of the clusters were located close to genes already known to be relevant for sarcomas, thus indicating a potential functional constraint, while others mapped to transcriptionally inactive chromatin domains enriched in heterochromatic sites. Of note, five neocentromeres were identified after analyzing 13 of the cases by fluorescent in situ hybridization. ChIP-on-chip analysis with antibodies against the centromeric protein CENP-A showed that they were a patchwork of small genomic segments derived from different chromosomes, likely joint to form a contiguous sequence during the amplification process.

Published
2014

19. Overexpression of schizophrenia susceptibility factor human complement C4Apromotes excessive synaptic loss and behavioral changes in mice

Author

Yilmaz, Melis, Yalcin, Esra, Presumey, Jessy, Aw, Ernest, Ma, Minghe, Whelan, Christopher W., Stevens, Beth, McCarroll, Steven A., and Carroll, Michael C.

Abstract

The complement component 4 (C4) gene is linked to schizophrenia and synaptic refinement. In humans, greater expression of C4Ain the brain is associated with an increased risk of schizophrenia. To investigate this genetic finding and address how C4Ashapes brain circuits in vivo, here, we generated a mouse model with primate-lineage-specific isoforms of C4, human C4Aand/or C4B. Human C4A bound synapses more efficiently than C4B. C4A(but not C4B) rescued the visual system synaptic refinement deficits of C4knockout mice. Intriguingly, mice without C4 had normal numbers of cortical synapses, which suggests that complement is not required for normal developmental synaptic pruning. However, overexpressing C4Ain mice reduced cortical synapse density, increased microglial engulfment of synapses and altered mouse behavior. These results suggest that increased C4A-mediated synaptic elimination results in abnormal brain circuits and behavior. Understanding pathological overpruning mechanisms has important therapeutic implications in disease conditions such as schizophrenia.

Published
2021
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20. Ultra-rare disruptive and damaging mutations influence educational attainment in the general population

Author

Ganna, Andrea, primary, Genovese, Giulio, additional, Howrigan, Daniel P, additional, Byrnes, Andrea, additional, Kurki, Mitja I, additional, Zekavat, Seyedeh M, additional, Whelan, Christopher W, additional, Kals, Mart, additional, Nivard, Michel G, additional, Bloemendal, Alex, additional, Bloom, Jonathan M, additional, Goldstein, Jacqueline I, additional, Poterba, Timothy, additional, Seed, Cotton, additional, Handsaker, Robert E, additional, Natarajan, Pradeep, additional, Mägi, Reedik, additional, Gage, Diane, additional, Robinson, Elise B, additional, Metspalu, Andres, additional, Salomaa, Veikko, additional, Suvisaari, Jaana, additional, Purcell, Shaun M, additional, Sklar, Pamela, additional, Kathiresan, Sekar, additional, Daly, Mark J, additional, McCarroll, Steven A, additional, Sullivan, Patrick F, additional, Palotie, Aarno, additional, Esko, Tõnu, additional, Hultman, Christina M, additional, and Neale, Benjamin M, additional

Published
2016
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21. Genomic organization and evolution of double minutes/homogeneously staining regions withMYCamplification in human cancer

Author

L'Abbate, Alberto, primary, Macchia, Gemma, additional, D'Addabbo, Pietro, additional, Lonoce, Angelo, additional, Tolomeo, Doron, additional, Trombetta, Domenico, additional, Kok, Klaas, additional, Bartenhagen, Christoph, additional, Whelan, Christopher W., additional, Palumbo, Orazio, additional, Severgnini, Marco, additional, Cifola, Ingrid, additional, Dugas, Martin, additional, Carella, Massimo, additional, De Bellis, Gianluca, additional, Rocchi, Mariano, additional, Carbone, Lucia, additional, and Storlazzi, Clelia Tiziana, additional

Published
2014
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24. Genomic organization and evolution of double minutes/homogeneously staining regions with MYC amplification in human cancer.

Author

L'Abbate, Alberto, Macchia, Gemma, D'Addabbo, Pietro, Lonoce, Angelo, Tolomeo, Doron, Trombetta, Domenico, Kok, Klaas, Bartenhagen, Christoph, Whelan, Christopher W., Palumbo, Orazio, Severgnini, Marco, Cifola, Ingrid, Dugas, Martin, Carella, Massimo, De Bellis, Gianluca, Rocchi, Mariano, Carbone, Lucia, and Storlazzi, Clelia Tiziana

Published
2014
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25. Ultra-rare disruptive and damaging mutations influence educational attainment in the general population

Author

Ganna, Andrea, Genovese, Giulio, Howrigan, Daniel P., Byrnes, Andrea, Kurki, Mitja, Zekavat, Seyedeh M., Whelan, Christopher W., Kals, Mart, Nivard, Michel G., Bloemendal, Alex, Bloom, Jonathan M., Goldstein, Jacqueline I., Poterba, Timothy, Seed, Cotton, Handsaker, Robert E., Natarajan, Pradeep, Mägi, Reedik, Gage, Diane, Robinson, Elise B., Metspalu, Andres, Salomaa, Veikko, Suvisaari, Jaana, Purcell, Shaun M., Sklar, Pamela, Kathiresan, Sekar, Daly, Mark J., McCarroll, Steven A., Sullivan, Patrick F., Palotie, Aarno, Esko, Tõnu, Hultman, Christina, and Neale, Benjamin M.

Abstract

Disruptive and damaging ultra-rare variants (URVs) in highly constrained (HC) genes are enriched in individuals with neurodevelopmental disorders. In the general population, this class of variants was associated with a decrease in years of education (YOE; −3.1 months; P-value=3.3×10−8). This effect was stronger among high brain-expressed genes and explained more YOE variance than pathogenic copy number variation, but less than common variants. Disruptive and damaging URVs in HC genes influence the determinants of YOE in the general population.

Published
2016
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26. Author Correction: A structural variation reference for medical and population genetics.

Author

Collins, Ryan L., Brand, Harrison, Karczewski, Konrad J., Zhao, Xuefang, Alföldi, Jessica, Francioli, Laurent C., Khera, Amit V., Lowther, Chelsea, Gauthier, Laura D., Wang, Harold, Watts, Nicholas A., Solomonson, Matthew, O'Donnell-Luria, Anne, Baumann, Alexander, Munshi, Ruchi, Walker, Mark, Whelan, Christopher W., Huang, Yongqing, Brookings, Ted, and Sharpe, Ted

Abstract

A Correction to this paper has been published: https://doi.org/10.1038/s41586-020-03176-6. [ABSTRACT FROM AUTHOR]

Published
2021
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