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27 results on '"Koval, Vyacheslav"'

1. A high-quality human reference panel reveals the complexity and distribution of genomic structural variants.

Author

Hehir-Kwa, Jayne Y, Marschall, Tobias, Kloosterman, Wigard P, Francioli, Laurent C, Baaijens, Jasmijn A, Dijkstra, Louis J, Abdellaoui, Abdel, Koval, Vyacheslav, Thung, Djie Tjwan, Wardenaar, René, Renkens, Ivo, Coe, Bradley P, Deelen, Patrick, de Ligt, Joep, Lameijer, Eric-Wubbo, van Dijk, Freerk, Hormozdiari, Fereydoun, Genome of the Netherlands Consortium, Uitterlinden, André G, van Duijn, Cornelia M, Eichler, Evan E, de Bakker, Paul IW, Swertz, Morris A, Wijmenga, Cisca, van Ommen, Gert-Jan B, Slagboom, P Eline, Boomsma, Dorret I, Schönhuth, Alexander, Ye, Kai, and Guryev, Victor

Subjects
Genome of the Netherlands Consortium, Chromosomes, Humans, RNA, Polymerase Chain Reaction, Sequence Analysis, DNA, Sequence Analysis, RNA, Computational Biology, Genomics, Gene Deletion, Genotype, Haplotypes, Linkage Disequilibrium, Polymorphism, Single Nucleotide, Genome, Human, Algorithms, Software, Netherlands, INDEL Mutation, Genomic Structural Variation, Sequence Analysis, DNA, Polymorphism, Single Nucleotide, Genome, Human
Abstract

Structural variation (SV) represents a major source of differences between individual human genomes and has been linked to disease phenotypes. However, the majority of studies provide neither a global view of the full spectrum of these variants nor integrate them into reference panels of genetic variation. Here, we analyse whole genome sequencing data of 769 individuals from 250 Dutch families, and provide a haplotype-resolved map of 1.9 million genome variants across 9 different variant classes, including novel forms of complex indels, and retrotransposition-mediated insertions of mobile elements and processed RNAs. A large proportion are previously under reported variants sized between 21 and 100 bp. We detect 4 megabases of novel sequence, encoding 11 new transcripts. Finally, we show 191 known, trait-associated SNPs to be in strong linkage disequilibrium with SVs and demonstrate that our panel facilitates accurate imputation of SVs in unrelated individuals.

Published
2016

2. Characteristics of de novo structural changes in the human genome

Author

Kloosterman, Wigard P, Francioli, Laurent C, Hormozdiari, Fereydoun, Marschall, Tobias, Hehir-Kwa, Jayne Y, Abdellaoui, Abdel, Lameijer, Eric-Wubbo, Moed, Matthijs H, Koval, Vyacheslav, Renkens, Ivo, van Roosmalen, Markus J, Arp, Pascal, Karssen, Lennart C, Coe, Bradley P, Handsaker, Robert E, Suchiman, Eka D, Cuppen, Edwin, Thung, Djie Tjwan, McVey, Mitch, Wendl, Michael C, Consortium, Genome of the Netherlands, Uitterlinden, André, van Duijn, Cornelia M, Swertz, Morris A, Wijmenga, Cisca, van Ommen, GertJan B, Slagboom, P Eline, Boomsma, Dorret I, Schönhuth, Alexander, Eichler, Evan E, de Bakker, Paul IW, Ye, Kai, and Guryev, Victor

Subjects
Genetics, Human Genome, Alleles, Amino Acid Sequence, Female, Genetic Variation, Genome, Human, Genomics, Haplotypes, Humans, INDEL Mutation, Male, Molecular Sequence Data, Mutation Rate, Polymorphism, Single Nucleotide, Retroelements, Sequence Alignment, Sequence Analysis, DNA, Genome of Netherlands Consortium, Biological Sciences, Medical and Health Sciences, Bioinformatics
Abstract

Small insertions and deletions (indels) and large structural variations (SVs) are major contributors to human genetic diversity and disease. However, mutation rates and characteristics of de novo indels and SVs in the general population have remained largely unexplored. We report 332 validated de novo structural changes identified in whole genomes of 250 families, including complex indels, retrotransposon insertions, and interchromosomal events. These data indicate a mutation rate of 2.94 indels (1-20 bp) and 0.16 SVs (>20 bp) per generation. De novo structural changes affect on average 4.1 kbp of genomic sequence and 29 coding bases per generation, which is 91 and 52 times more nucleotides than de novo substitutions, respectively. This contrasts with the equal genomic footprint of inherited SVs and substitutions. An excess of structural changes originated on paternal haplotypes. Additionally, we observed a nonuniform distribution of de novo SVs across offspring. These results reveal the importance of different mutational mechanisms to changes in human genome structure across generations.

Published
2015

3. Long-range percolation on the hierarchical lattice

Author

Koval, Vyacheslav, Meester, Ronald, and Trapman, Pieter

Subjects
Mathematics - Probability, 60K35(Primary) 82B28(Secondary)
Abstract

We study long-range percolation on the hierarchical lattice of order $N$, where any edge of length $k$ is present with probability $p_k=1-\exp(-\beta^{-k} \alpha)$, independently of all other edges. For fixed $\beta$, we show that the critical value $\alpha_c(\beta)$ is non-trivial if and only if $N < \beta < N^2$. Furthermore, we show uniqueness of the infinite component and continuity of the percolation probability and of $\alpha_c(\beta)$ as a function of $\beta$. This means that the phase diagram of this model is well understood., Comment: 24 pages

Published
2010
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4. WGS-based telomere length analysis in Dutch family trios implicates stronger maternal inheritance and a role for RRM1 gene

Author

Nersisyan, Lilit, Nikoghosyan, Maria, Arakelyan, Arsen, Francioli, Laurent, Menelaou, A. (Androniki), Pulit, S.L. (Sara L.), Elbers, C.C. (Clara C.), Kloosterman, Wigard, van Setten, J. (Jessica), Nijman, Isaac, Renkens, Ivo, de Bakker, P.I.W. (Paul I. W.), Dijk, Freerk, Neerincx, Pieter, Deelen, Patrick, Kanterakis, Alexandros, Dijkstra, Martijn, Byelas, H. (Heorhiy), van der Velde, K.J. (K. Joeri), Platteel, Mathieu, Swertz, M.A. (Morris A.), Wijmenga, Cisca, Palamara, P.F. (Pier Francesco), Pe’er, I. (Itsik), Ye, K. (Kai), Lameijer, Eric-Wubbo, Moed, M.H. (Matthijs H.), Beekman, M. (Marian), Craen, Anton, Suchiman, H.E.D. (H. Eka D.), Slagboom, Eline, Guryev, Victor, Abdellaoui, Abdel, Jan Hottenga, J. (Jouke), Kattenberg, M. (Mathijs), Willemsen, Gonneke, Boomsma, Dorret, van Leeuwen, E.M. (Elisabeth M.), Karssen, Lennart, Amin, N. (Najaf), Rivadeneira, F. (Fernando), Isaacs, A. (Aaron), Hofman, A. (Albert), Uitterlinden, André, Duijn, Cornelia, van Oven, M. (Mannis), Kayser, M. (Manfred), Vermaat, Martijn, Laros, Jeroen, Dunnen, Johan, Enckevort, David, Mei, Hailiang, Li, M. (Mingkun), Stoneking, M. (Mark), Schaik, Barbera, Bot, Jan, Marschall, Tobias, Schönhuth, Alexander, Hehir-Kwa, Jayne, Handsaker, Robert, Polak, P. (Paz), Sohail, M. (Mashaal), Vuzman, D. (Dana), Estrada, Karol, McCarroll, S.A. (Steven A.), Sunyaev, S.R. (Shamil R.), Hormozdiari, Fereydoun, Koval, Vyacheslav, Medina-Gomez, C. (Carolina), Oostra, B. (Ben), Veldink, Jan, van den Berg, L.H. (Leonard H.), Pitts, S.J. (Steven J.), Potluri, S. (Shobha), Sundar, P. (Purnima), Cox, D.R. (David R.), Knijff, Peter, Li, Q. (Qibin), Li, Y. (Yingrui), Du, Yuanping, Chen, Ruoyan, Cao, H. (Hongzhi), Wang, J. (Jun), Li, N. (Ning), Cao, S. (Sujie), Bovenberg, Jasper, Ommen, Gert-Jan, The Genome of the Netherlands Consortium, Biological Psychology, APH - Health Behaviors & Chronic Diseases, APH - Personalized Medicine, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Mental Health, APH - Methodology, Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Department of Health and Life Sciences, Groningen Research Institute for Asthma and COPD (GRIAC), Stem Cell Aging Leukemia and Lymphoma (SALL), Experimental Immunology, CCA - Cancer biology and immunology, Epidemiology and Data Science, Amsterdam Gastroenterology Endocrinology Metabolism, Epidemiology, Internal Medicine, Genetic Identification, Clinical Genetics, and Genome of the Netherlands Consortium

Subjects
Male, Telomere Homeostasis/genetics, Netherlands Twin Register (NTR), Non-Mendelian inheritance, lcsh:Medicine, Datasets as Topic, Ribonucleoside Diphosphate Reductase/genetics, Genome of the Netherlands consortium, Genome informatics, Genome, 0302 clinical medicine, Models, 80 and over, Inheritance Patterns, lcsh:Science, Child, Netherlands, Genetics, Aged, 80 and over, 0303 health sciences, Multidisciplinary, Age Factors, Functional genomics, Single Nucleotide, ASSOCIATION, Telomere, Middle Aged, 030220 oncology & carcinogenesis, Trait, Female, Maternal Inheritance, Biotechnology, Maternal Age, Adult, Ribonucleoside Diphosphate Reductase, Adolescent, Offspring, PROTEINS, Quantitative trait locus, Biology, Polymorphism, Single Nucleotide, Article, Paternal Age, 03 medical and health sciences, Young Adult, Sex Factors, LUNG-CANCER, Genetic, Humans, Polymorphism, Telomere/metabolism, General, Gene, METAANALYSIS, 030304 developmental biology, Aged, Whole genome sequencing, Models, Genetic, Whole Genome Sequencing, Human Genome, lcsh:R, Telomere Homeostasis, SIZE, SUBUNIT, CELLS, Linear Models, lcsh:Q, Genome-Wide Association Study
Abstract

Telomere length (TL) regulation is an important factor in ageing, reproduction and cancer development. Genetic, hereditary and environmental factors regulating TL are currently widely investigated, however, their relative contribution to TL variability is still understudied. We have used whole genome sequencing data of 250 family trios from the Genome of the Netherlands project to perform computational measurement of TL and a series of regression and genome-wide association analyses to reveal TL inheritance patterns and associated genetic factors. Our results confirm that TL is a largely heritable trait, primarily with mother’s, and, to a lesser extent, with father’s TL having the strongest influence on the offspring. In this cohort, mother’s, but not father’s age at conception was positively linked to offspring TL. Age-related TL attrition of 40 bp/year had relatively small influence on TL variability. Finally, we have identified TL-associated variations in ribonuclease reductase catalytic subunit M1 (RRM1 gene), which is known to regulate telomere maintenance in yeast. We also highlight the importance of multivariate approach and the limitations of existing tools for the analysis of TL as a polygenic heritable quantitative trait.

Published
2019

5. Integrated clinical and omics approach to rare diseases : Novel genes and oligogenic inheritance in holoprosencephaly

Author

Kim, Artem, Savary, Clara, Dubourg, Christèle, Carré, Wilfrid, Mouden, Charlotte, Hamdi-Rozé, Houda, Guyodo, Hélène, Douce, Jerome Le, Génin, Emmanuelle, Campion, Dominique, Dartigues, Jean François, Deleuze, Jean François, Lambert, Jean Charles, Redon, Richard, Ludwig, Thomas, Grenier-Boley, Benjamin, Letort, Sébastien, Lindenbaum, Pierre, Meyer, Vincent, Quenez, Olivier, Dina, Christian, Bellenguez, Céline, Charbonnier-Le Clézio, Camille, Giemza, Joanna, Chatel, Stéphanie, Férec, Claude, Le Marec, Hervé, Letenneur, Luc, Nicolas, Gaël, Rouault, Karen, Bacq, Delphine, Boland, Anne, Lechner, Doris, Wijmenga, Cisca, Swertz, Morris A., Eline Slagboom, P., Van Ommen, Gert Jan B., Van Duijn, Cornelia M., Boomsma, Dorret I., De Bakker, Paul I.W., Bovenberg, Jasper A., De Craen, Anton J.M., Beekman, Marian, Hofman, Albert, Willemsen, Gonneke, Wolffenbuttel, Bruce, Platteel, Mathieu, Du, Yuanping, Chen, Ruoyan, Cao, Hongzhi, Cao, Rui, Sun, Yushen, Sujie Cao, Jeremy, Van Dijk, Freerk, Neerincx, Pieter B.T., Deelen, Patrick, Dijkstra, Martijn, Byelas, George, Kanterakis, Alexandros, Bot, Jan, Ye, Kai, Lameijer, Eric Wubbo, Vermaat, Martijn, Laros, Jeroen F.J., Den Dunnen, Johan T., De Knijff, Peter, Karssen, Lennart C., Van Leeuwen, Elisa M., Amin, Najaf, Koval, Vyacheslav, Rivadeneira, Fernando, Estrada, Karol, Hehir-Kwa, Jayne Y., De Ligt, Joep, Abdellaoui, Abdel, Hottenga, Jouke Jan, Mathijs Kattenberg, V., Van Enckevort, David, Mei, Hailiang, Santcroos, Mark, Van Schaik, Barbera D.C., Handsaker, Robert E., McCarroll, Steven A., Eichler, Evan E., Ko, Arthur, Sudmant, Peter, Francioli, Laurent C., Kloosterman, Wigard P., Nijman, Isaac J., Guryev, Victor, Pasquier, Laurent, Flori, Elisabeth, Gonzales, Marie, Bénéteau, Claire, Boute, Odile, Attié-Bitach, Tania, Roume, Joelle, Goujon, Louise, Akloul, Linda, Odent, Sylvie, Watrin, Erwan, Dupé, Valérie, De Tayrac, Marie, David, Véronique, Kim, Artem, Savary, Clara, Dubourg, Christèle, Carré, Wilfrid, Mouden, Charlotte, Hamdi-Rozé, Houda, Guyodo, Hélène, Douce, Jerome Le, Génin, Emmanuelle, Campion, Dominique, Dartigues, Jean François, Deleuze, Jean François, Lambert, Jean Charles, Redon, Richard, Ludwig, Thomas, Grenier-Boley, Benjamin, Letort, Sébastien, Lindenbaum, Pierre, Meyer, Vincent, Quenez, Olivier, Dina, Christian, Bellenguez, Céline, Charbonnier-Le Clézio, Camille, Giemza, Joanna, Chatel, Stéphanie, Férec, Claude, Le Marec, Hervé, Letenneur, Luc, Nicolas, Gaël, Rouault, Karen, Bacq, Delphine, Boland, Anne, Lechner, Doris, Wijmenga, Cisca, Swertz, Morris A., Eline Slagboom, P., Van Ommen, Gert Jan B., Van Duijn, Cornelia M., Boomsma, Dorret I., De Bakker, Paul I.W., Bovenberg, Jasper A., De Craen, Anton J.M., Beekman, Marian, Hofman, Albert, Willemsen, Gonneke, Wolffenbuttel, Bruce, Platteel, Mathieu, Du, Yuanping, Chen, Ruoyan, Cao, Hongzhi, Cao, Rui, Sun, Yushen, Sujie Cao, Jeremy, Van Dijk, Freerk, Neerincx, Pieter B.T., Deelen, Patrick, Dijkstra, Martijn, Byelas, George, Kanterakis, Alexandros, Bot, Jan, Ye, Kai, Lameijer, Eric Wubbo, Vermaat, Martijn, Laros, Jeroen F.J., Den Dunnen, Johan T., De Knijff, Peter, Karssen, Lennart C., Van Leeuwen, Elisa M., Amin, Najaf, Koval, Vyacheslav, Rivadeneira, Fernando, Estrada, Karol, Hehir-Kwa, Jayne Y., De Ligt, Joep, Abdellaoui, Abdel, Hottenga, Jouke Jan, Mathijs Kattenberg, V., Van Enckevort, David, Mei, Hailiang, Santcroos, Mark, Van Schaik, Barbera D.C., Handsaker, Robert E., McCarroll, Steven A., Eichler, Evan E., Ko, Arthur, Sudmant, Peter, Francioli, Laurent C., Kloosterman, Wigard P., Nijman, Isaac J., Guryev, Victor, Pasquier, Laurent, Flori, Elisabeth, Gonzales, Marie, Bénéteau, Claire, Boute, Odile, Attié-Bitach, Tania, Roume, Joelle, Goujon, Louise, Akloul, Linda, Odent, Sylvie, Watrin, Erwan, Dupé, Valérie, De Tayrac, Marie, and David, Véronique

Published
2019

6. Integrated clinical and omics approach to rare diseases: Novel genes and oligogenic inheritance in holoprosencephaly

Author

CMM Groep Kaaij, Genetica Klinische Genetica, Cancer, CMM Groep De Ridder, Child Health, CMM Groep Kloosterman, CMM USEQ Facility, Hubrecht Institute with UMC, Kim, Artem, Savary, Clara, Dubourg, Christèle, Carré, Wilfrid, Mouden, Charlotte, Hamdi-Rozé, Houda, Guyodo, Hélène, Douce, Jerome Le, Génin, Emmanuelle, Campion, Dominique, Dartigues, Jean François, Deleuze, Jean François, Lambert, Jean Charles, Redon, Richard, Ludwig, Thomas, Grenier-Boley, Benjamin, Letort, Sébastien, Lindenbaum, Pierre, Meyer, Vincent, Quenez, Olivier, Dina, Christian, Bellenguez, Céline, Charbonnier-Le Clézio, Camille, Giemza, Joanna, Chatel, Stéphanie, Férec, Claude, Le Marec, Hervé, Letenneur, Luc, Nicolas, Gaël, Rouault, Karen, Bacq, Delphine, Boland, Anne, Lechner, Doris, Wijmenga, Cisca, Swertz, Morris A., Eline Slagboom, P., Van Ommen, Gert Jan B., Van Duijn, Cornelia M., Boomsma, Dorret I., De Bakker, Paul I.W., Bovenberg, Jasper A., De Craen, Anton J.M., Beekman, Marian, Hofman, Albert, Willemsen, Gonneke, Wolffenbuttel, Bruce, Platteel, Mathieu, Du, Yuanping, Chen, Ruoyan, Cao, Hongzhi, Cao, Rui, Sun, Yushen, Sujie Cao, Jeremy, Van Dijk, Freerk, Neerincx, Pieter B.T., Deelen, Patrick, Dijkstra, Martijn, Byelas, George, Kanterakis, Alexandros, Bot, Jan, Ye, Kai, Lameijer, Eric Wubbo, Vermaat, Martijn, Laros, Jeroen F.J., Den Dunnen, Johan T., De Knijff, Peter, Karssen, Lennart C., Van Leeuwen, Elisa M., Amin, Najaf, Koval, Vyacheslav, Rivadeneira, Fernando, Estrada, Karol, Hehir-Kwa, Jayne Y., De Ligt, Joep, Abdellaoui, Abdel, Hottenga, Jouke Jan, Mathijs Kattenberg, V., Van Enckevort, David, Mei, Hailiang, Santcroos, Mark, Van Schaik, Barbera D.C., Handsaker, Robert E., McCarroll, Steven A., Eichler, Evan E., Ko, Arthur, Sudmant, Peter, Francioli, Laurent C., Kloosterman, Wigard P., Nijman, Isaac J., Guryev, Victor, Pasquier, Laurent, Flori, Elisabeth, Gonzales, Marie, Bénéteau, Claire, Boute, Odile, Attié-Bitach, Tania, Roume, Joelle, Goujon, Louise, Akloul, Linda, Odent, Sylvie, Watrin, Erwan, Dupé, Valérie, De Tayrac, Marie, David, Véronique, CMM Groep Kaaij, Genetica Klinische Genetica, Cancer, CMM Groep De Ridder, Child Health, CMM Groep Kloosterman, CMM USEQ Facility, Hubrecht Institute with UMC, Kim, Artem, Savary, Clara, Dubourg, Christèle, Carré, Wilfrid, Mouden, Charlotte, Hamdi-Rozé, Houda, Guyodo, Hélène, Douce, Jerome Le, Génin, Emmanuelle, Campion, Dominique, Dartigues, Jean François, Deleuze, Jean François, Lambert, Jean Charles, Redon, Richard, Ludwig, Thomas, Grenier-Boley, Benjamin, Letort, Sébastien, Lindenbaum, Pierre, Meyer, Vincent, Quenez, Olivier, Dina, Christian, Bellenguez, Céline, Charbonnier-Le Clézio, Camille, Giemza, Joanna, Chatel, Stéphanie, Férec, Claude, Le Marec, Hervé, Letenneur, Luc, Nicolas, Gaël, Rouault, Karen, Bacq, Delphine, Boland, Anne, Lechner, Doris, Wijmenga, Cisca, Swertz, Morris A., Eline Slagboom, P., Van Ommen, Gert Jan B., Van Duijn, Cornelia M., Boomsma, Dorret I., De Bakker, Paul I.W., Bovenberg, Jasper A., De Craen, Anton J.M., Beekman, Marian, Hofman, Albert, Willemsen, Gonneke, Wolffenbuttel, Bruce, Platteel, Mathieu, Du, Yuanping, Chen, Ruoyan, Cao, Hongzhi, Cao, Rui, Sun, Yushen, Sujie Cao, Jeremy, Van Dijk, Freerk, Neerincx, Pieter B.T., Deelen, Patrick, Dijkstra, Martijn, Byelas, George, Kanterakis, Alexandros, Bot, Jan, Ye, Kai, Lameijer, Eric Wubbo, Vermaat, Martijn, Laros, Jeroen F.J., Den Dunnen, Johan T., De Knijff, Peter, Karssen, Lennart C., Van Leeuwen, Elisa M., Amin, Najaf, Koval, Vyacheslav, Rivadeneira, Fernando, Estrada, Karol, Hehir-Kwa, Jayne Y., De Ligt, Joep, Abdellaoui, Abdel, Hottenga, Jouke Jan, Mathijs Kattenberg, V., Van Enckevort, David, Mei, Hailiang, Santcroos, Mark, Van Schaik, Barbera D.C., Handsaker, Robert E., McCarroll, Steven A., Eichler, Evan E., Ko, Arthur, Sudmant, Peter, Francioli, Laurent C., Kloosterman, Wigard P., Nijman, Isaac J., Guryev, Victor, Pasquier, Laurent, Flori, Elisabeth, Gonzales, Marie, Bénéteau, Claire, Boute, Odile, Attié-Bitach, Tania, Roume, Joelle, Goujon, Louise, Akloul, Linda, Odent, Sylvie, Watrin, Erwan, Dupé, Valérie, De Tayrac, Marie, and David, Véronique

Published
2019

7. Transmission of human mtDNA heteroplasmy in the Genome of the Netherlands families: support for a variable-size bottleneck

Author

Li, Mingkun, Rothwell, Rebecca, Vermaat, Martijn, Wachsmuth, Manja, Schröder, Roland, Laros, Jeroen F J, Van Oven, Mannis, De Bakker, Paul I W, Bovenberg, Jasper A., Van Duijn, Cornelia M., Van Ommen, Gert Jan B, Slagboom, P. Eline, Swertz, Morris A., Wijmenga, Cisca, Kayser, Manfred, Boomsma, Dorret I., Zöllner, Sebastian, De Knijff, Peter, Stoneking, Mark, De Craen, Anton J M, Beekman, Marian, Hofman, Albert, Willemsen, Gonneke, Wolffenbuttel, Bruce, Platteel, Mathieu, Du, Yuanping, Chen, Ruoyan, Cao, Hongzhi, Cao, Rui, Sun, Yushen, Cao, Jeremy Sujie, Van Dijk, Freerk, Neerincx, Pieter B T, Deelen, Patrick, Dijkstra, Martijn, Byelas, George, Kanterakis, Alexandros, Bot, Jan, Ye, Kai, Lameijer, Eric Wubbo, Den Dunnen, Johan T., Karssen, Lennart C., Van Leeuwen, Elisa M., Amin, Najaf, Koval, Vyacheslav, Rivadeneira, Fernando, Estrada, Karol, Hehir-Kwa, Jayne Y., De Ligt, Joep, Abdellaoui, Abdel, Hottenga, Jouke Jan, Kattenberg, V. Mathijs, Van Enckevort, David, Mei, Hailiang, Santcroos, Mark, Van Schaik, Barbera D C, Handsaker, Robert E., McCarroll, Steven A., Eichler, Evan E., Ko, Arthur, Sudmant, Peter, Francioli, Laurent C., Kloosterman, Wigard P., Nijman, Isaac J., Guryev, Victor, Genetic Identification, Epidemiology, Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Biological Psychology, EMGO+ - Quality of Care, and Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep

Subjects
Male, Netherlands Twin Register (NTR), 0301 basic medicine, LEVEL, Inheritance Patterns, Twins, Twin Study, POINT MUTATIONS, Genome, Gene Frequency, Paternal mtDNA transmission, Genetics(clinical), Non-U.S. Gov't, Genetics (clinical), Netherlands, Genetics, Research Support, Non-U.S. Gov't, PURIFYING SELECTION, MITOCHONDRIAL-DNA MUTATIONS, RANDOM GENETIC DRIFT, HUMAN-DISEASE, Heteroplasmy, Female, Mitochondrial DNA, TISSUES, OOCYTES, Biology, Research Support, INHERITANCE, DNA, Mitochondrial, White People, Genetic Heterogeneity, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Journal Article, Humans, Family, Selection, Genetic, Allele, Allele frequency, Alleles, Models, Statistical, Polymorphism, Genetic, Models, Genetic, Research, Twin study, Minor allele frequency, 030104 developmental biology, Mutation, MELAS SYNDROME
Abstract

Although previous studies have documented a bottleneck in the transmission of mtDNA genomes from mothers to offspring, several aspects remain unclear, including the size and nature of the bottleneck. Here, we analyze the dynamics of mtDNA heteroplasmy transmission in the Genomes of the Netherlands (GoNL) data, which consists of complete mtDNA genome sequences from 228 trios, eight dizygotic (DZ) twin quartets, and 10 monozygotic (MZ) twin quartets. Using a minor allele frequency (MAF) threshold of 2%, we identified 189 heteroplasmies in the trio mothers, of which 59% were transmitted to offspring, and 159 heteroplasmies in the trio offspring, of which 70% were inherited from the mothers. MZ twin pairs exhibited greater similarity in MAF at heteroplasmic sites than DZ twin pairs, suggesting that the heteroplasmy MAF in the oocyte is the major determinant of the heteroplasmy MAF in the offspring. We used a likelihood method to estimate the effective number of mtDNA genomes transmitted to offspring under different bottleneck models; a variable bottleneck size model provided the best fit to the data, with an estimated mean of nine individual mtDNA genomes transmitted. We also found evidence for negative selection during transmission against novel heteroplasmies (in which the minor allele has never been observed in polymorphism data). These novel heteroplasmies are enhanced for tRNA and rRNA genes, and mutations associated with mtDNA diseases frequently occur in these genes. Our results thus suggest that the female germ line is able to recognize and select against deleterious heteroplasmies.

Published
2016

8. A high-quality human reference panel reveals the complexity and distribution of genomic structural variants

Author

Hehir-Kwa, Jayne, Marschall, Tobias, Kloosterman, Wigard, Francioli, Laurent, Baaijens, Jasmijn, Dijkstra, Louis, Abdellaoui, Abdel, Koval, Vyacheslav, Thung, (), Djie Tjwan, Wardenaar, René, Renkens, Ivo, Coe, Bradley, Deelen, Patrick, Ligt, Joep, Lameijer, Eric-Wubbo, Dijk, Freerk, Hormozdiari, Fereydoun, Uitterlinden, André, Duijn, Cornelia, Eichler, Evan, Bakker, Paul, Swertz, Morris, Wijmenga, Cisca, Ommen, Gert-Jan, Slagboom, Eline, Boomsma, Dorret, Schönhuth, Alexander, Ye, Kai, Guryev, Victor, Bovenberg, Jasper, Craen, Anton, Beekman, Marian, Hofman, Albert, Willemsen, Gonneke, Wolffenbuttel, Bruce, Platteel, Mathieu, Du, Yuanping, Chen, Ruoyan, Cao, Hongzhi, Cao, Rui, Sun, Yushen, Cao, Jeremy Sujie, Neerincx, Pieter, Dijkstra, Martijn, Byelas, George, Kanterakis, Alexandros, Bot, Jan, Vermaat, Martijn, Laros, Jeroen, Dunnen, Johan, Knijff, Peter, Karssen, Lennart, van Leeuwen, Elisa, Amin, Najaf, Rivadeneira, Fernando, Estrada, Karol, Hottenga, Jouke-Jan, Kattenberg, Mathijs, Enckevort, David, Mei, Hailiang, Santcroos, Mark, Schaik, Barbera, Handsaker, Robert, McCarroll, Steven, Ko, Arthur, Sudmant, Peter, Nijman, Isaac, Internal Medicine, Epidemiology, Biological Psychology, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Bioinformatics, Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Stem Cell Aging Leukemia and Lymphoma (SALL), Groningen Research Institute for Asthma and COPD (GRIAC), Adult Psychiatry, Epidemiology and Data Science, APH - Methodology, AII - Inflammatory diseases, AII - Cancer immunology, CCA - Cancer biology and immunology, APH - Personalized Medicine, ACS - Amsterdam Cardiovascular Sciences, AII - Amsterdam institute for Infection and Immunity, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, ANS - Amsterdam Neuroscience, and CCA -Cancer Center Amsterdam

Subjects
0301 basic medicine, Netherlands Twin Register (NTR), Chemistry(all), IMPACT, General Physics and Astronomy, SUSCEPTIBILITY, Genome informatics, Biochemistry, Genome, Polymerase Chain Reaction, Linkage Disequilibrium, DISEASE, INDEL Mutation, IMPUTATION, 2.1 Biological and endogenous factors, Copy-number variation, Aetiology, Netherlands, Genetics, Multidisciplinary, Genomics, Single Nucleotide, ASSOCIATION, Genome of the Netherlands Consortium, Sequence Analysis, Algorithms, Human, Biotechnology, Genotype, DATABASE, Science, Genomic Structural Variation, Computational biology, Physics and Astronomy(all), Biology, Polymorphism, Single Nucleotide, General Biochemistry, Genetics and Molecular Biology, Article, Chromosomes, GENETIC ARCHITECTURE, Structural variation, 03 medical and health sciences, Journal Article, Humans, Polymorphism, COPY NUMBER VARIATION, Whole genome sequencing, Biochemistry, Genetics and Molecular Biology(all), Genome, Human, Sequence Analysis, RNA, DELETION, Human Genome, Computational Biology, General Chemistry, Sequence Analysis, DNA, DNA, 030104 developmental biology, TRIOS, Haplotypes, Next-generation sequencing, RNA, Human genome, Generic health relevance, Imputation (genetics), Gene Deletion, Software, Genetics and Molecular Biology(all)
Abstract

Structural variation (SV) represents a major source of differences between individual human genomes and has been linked to disease phenotypes. However, the majority of studies provide neither a global view of the full spectrum of these variants nor integrate them into reference panels of genetic variation. Here, we analyse whole genome sequencing data of 769 individuals from 250 Dutch families, and provide a haplotype-resolved map of 1.9 million genome variants across 9 different variant classes, including novel forms of complex indels, and retrotransposition-mediated insertions of mobile elements and processed RNAs. A large proportion are previously under reported variants sized between 21 and 100 bp. We detect 4 megabases of novel sequence, encoding 11 new transcripts. Finally, we show 191 known, trait-associated SNPs to be in strong linkage disequilibrium with SVs and demonstrate that our panel facilitates accurate imputation of SVs in unrelated individuals., Structural variants (SVs) are prevalent in genomes of the general population. Here, Guryev and The Genome of the Netherlands Consortium describe the reference panel of haplotype-resolved SVs from 769 individuals from 250 Dutch families and show its utility for studying heritable traits.

Published
2016

9. Characteristics of de novo structural changes in the human genome

Author

Kloosterman, Wigard P., Francioli, Laurent C., Hormozdiari, Fereydoun, Marschall, Tobias, Hehir-Kwa, Jayne Y., Abdellaoui, Abdel, Lameijer, Eric Wubbo, Moed, Matthijs H., Koval, Vyacheslav, Renkens, Ivo, Van Roosmalen, Markus J., Arp, Pascal, Karssen, Lennart C., Coe, Bradley P., Handsaker, Robert E., Suchiman, Eka D., Cuppen, Edwin, Thung, Djie Tjwan, McVey, Mitch, Wendl, Michael C., Uitterlinden, André, Van Duijn, Cornelia M., Swertz, Morris A., Wijmenga, Cisca, Van Ommen, Gert Jan B, Slagboom, P. Eline, Boomsma, Dorret I., Schönhuth, Alexander, Eichler, Evan E., De Bakker, Paul I W, Ye, Kai, Guryev, Victor, Bovenberg, Jasper A., De Craen, Anton J M, Beekman, Marian, Hofman, Albert, Willemsen, Gonneke, Wolffenbuttel, Bruce, Platteel, Mathieu, Du, Yuanping, Chen, Ruoyan, Cao, Hongzhi, Cao, Rui, Sun, Yushen, Cao, Jeremy Sujie, Van Dijk, Freerk, Neerincx, Pieter B T, Deelen, Patrick, Dijkstra, Martijn, Byelas, George, Kanterakis, Alexandros, Bot, Jan, Vermaat, Martijn, Laros, Jeroen F J, Den Dunnen, Johan T., De Knijff, Peter, Van Leeuwen, Elisa M., Amin, Najaf, Rivadeneira, Fernando, Estrada, Karol, De Ligt, Joep, Hottenga, Jouke Jan, Kattenberg, V. Mathijs, Van Enckevort, David, Mei, Hailiang, Santcroos, Mark, Van Schaik, Barbera D C, McCarroll, Steven A., Ko, Arthur, Sudmant, Peter, Nijman, Isaac J., Adult Psychiatry, Epidemiology and Data Science, ACS - Amsterdam Cardiovascular Sciences, AII - Amsterdam institute for Infection and Immunity, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, ANS - Amsterdam Neuroscience, CCA -Cancer Center Amsterdam, Biological Psychology, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, Internal Medicine, Epidemiology, Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Stem Cell Aging Leukemia and Lymphoma (SALL), and Groningen Research Institute for Asthma and COPD (GRIAC)

Subjects
Male, Netherlands Twin Register (NTR), Mutation rate, INTELLECTUAL DISABILITY, Retrotransposon, Genome of Netherlands Consortium, VARIANTS, Medical and Health Sciences, Genome, 0302 clinical medicine, INDEL Mutation, Mutation Rate, Genetics(clinical), Copy-number variation, Genetics (clinical), Genetics, 0303 health sciences, education.field_of_study, food and beverages, Genomics, Single Nucleotide, Biological Sciences, Female, Sequence Analysis, Human, Retroelements, SEQUENCING DATA, Bioinformatics, Molecular Sequence Data, Population, MUTATION-RATES, POPULATION-SCALE, Biology, Polymorphism, Single Nucleotide, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Humans, Amino Acid Sequence, Polymorphism, Indel, education, Alleles, 030304 developmental biology, COPY NUMBER VARIATION, INDIVIDUAL HUMAN, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], IDENTIFICATION, Genome, Human, Research, Human Genome, Genetic Variation, Sequence Analysis, DNA, DNA, GENE, Haplotypes, DISCOVERY, Human genome, Sequence Alignment, 030217 neurology & neurosurgery
Abstract

Contains fulltext : 154750.pdf (Publisher’s version ) (Open Access) Small insertions and deletions (indels) and large structural variations (SVs) are major contributors to human genetic diversity and disease. However, mutation rates and characteristics of de novo indels and SVs in the general population have remained largely unexplored. We report 332 validated de novo structural changes identified in whole genomes of 250 families, including complex indels, retrotransposon insertions, and interchromosomal events. These data indicate a mutation rate of 2.94 indels (1-20 bp) and 0.16 SVs (>20 bp) per generation. De novo structural changes affect on average 4.1 kbp of genomic sequence and 29 coding bases per generation, which is 91 and 52 times more nucleotides than de novo substitutions, respectively. This contrasts with the equal genomic footprint of inherited SVs and substitutions. An excess of structural changes originated on paternal haplotypes. Additionally, we observed a nonuniform distribution of de novo SVs across offspring. These results reveal the importance of different mutational mechanisms to changes in human genome structure across generations. 01 juni 2015

Published
2015

10. A high-quality human reference panel reveals the complexity and distribution of genomic structural variants

Author

Hehir-Kwa, Jayne Y., Marschall, Tobias, Kloosterman, Wigard P., Francioli, Laurent C., Baaijens, Jasmijn A., Dijkstra, Louis J., Abdellaoui, Abdel, Koval, Vyacheslav, Thung, Djie Tjwan, Wardenaar, René, Renkens, Ivo, Coe, Bradley P., Deelen, Patrick, De Ligt, Joep, Lameijer, Eric Wubbo, Van Dijk, Freerk, Hormozdiari, Fereydoun, Uitterlinden, André G., Van Duijn, Cornelia M., Eichler, Evan E., De Bakker, Paul I.W., Swertz, Morris A., Wijmenga, Cisca, Van Ommen, Gert Jan B, Slagboom, P. Eline, Boomsma, Dorret I., Schönhuth, Alexander, Ye, Kai, Guryev, Victor, Bovenberg, Jasper A., De Craen, Anton J M, Beekman, Marian, Hofman, Albert, Willemsen, Gonneke, Wolffenbuttel, Bruce, Platteel, Mathieu, Du, Yuanping, Chen, Ruoyan, Cao, Hongzhi, Cao, Rui, Sun, Yushen, Cao, Jeremy Sujie, Neerincx, Pieter B T, Dijkstra, Martijn, Byelas, George, Kanterakis, Alexandros, Bot, Jan, Vermaat, Martijn, Laros, Jeroen F., den Dunnen, Johan T., De Knijff, Peter, Karssen, Lennart C., Van Leeuwen, Elisa M., Amin, Najaf, Rivadeneira, Fernando, Estrada, Karol, Hottenga, Jouke-Jan, Kattenberg, V. Mathijs, Van Enckevort, David, Mei, Hailiang, Santcroos, Mark, Van Schaik, Barbera D C, Handsaker, Robert E., McCarroll, Steven A., Ko, Arthur, Sudmant, Peter, Nijman, Isaac J., Hehir-Kwa, Jayne Y., Marschall, Tobias, Kloosterman, Wigard P., Francioli, Laurent C., Baaijens, Jasmijn A., Dijkstra, Louis J., Abdellaoui, Abdel, Koval, Vyacheslav, Thung, Djie Tjwan, Wardenaar, René, Renkens, Ivo, Coe, Bradley P., Deelen, Patrick, De Ligt, Joep, Lameijer, Eric Wubbo, Van Dijk, Freerk, Hormozdiari, Fereydoun, Uitterlinden, André G., Van Duijn, Cornelia M., Eichler, Evan E., De Bakker, Paul I.W., Swertz, Morris A., Wijmenga, Cisca, Van Ommen, Gert Jan B, Slagboom, P. Eline, Boomsma, Dorret I., Schönhuth, Alexander, Ye, Kai, Guryev, Victor, Bovenberg, Jasper A., De Craen, Anton J M, Beekman, Marian, Hofman, Albert, Willemsen, Gonneke, Wolffenbuttel, Bruce, Platteel, Mathieu, Du, Yuanping, Chen, Ruoyan, Cao, Hongzhi, Cao, Rui, Sun, Yushen, Cao, Jeremy Sujie, Neerincx, Pieter B T, Dijkstra, Martijn, Byelas, George, Kanterakis, Alexandros, Bot, Jan, Vermaat, Martijn, Laros, Jeroen F., den Dunnen, Johan T., De Knijff, Peter, Karssen, Lennart C., Van Leeuwen, Elisa M., Amin, Najaf, Rivadeneira, Fernando, Estrada, Karol, Hottenga, Jouke-Jan, Kattenberg, V. Mathijs, Van Enckevort, David, Mei, Hailiang, Santcroos, Mark, Van Schaik, Barbera D C, Handsaker, Robert E., McCarroll, Steven A., Ko, Arthur, Sudmant, Peter, and Nijman, Isaac J.

Published
2016

11. A high-quality human reference panel reveals the complexity and distribution of genomic structural variants

Author

Genetica, CMM Groep Kloosterman, Child Health, Cancer, CMM Groep Kaaij, CMM Groep Cuppen, CMM Groep De Ridder, Epi Methoden Team 2, Infection & Immunity, Circulatory Health, Hubrecht Institute with UMC, Genetica Medische Informatica, Genetica Sectie Genoomdiagnostiek, Hehir-Kwa, Jayne Y., Marschall, Tobias, Kloosterman, Wigard P., Francioli, Laurent C., Baaijens, Jasmijn A., Dijkstra, Louis J., Abdellaoui, Abdel, Koval, Vyacheslav, Thung, Djie Tjwan, Wardenaar, René, Renkens, Ivo, Coe, Bradley P., Deelen, Patrick, De Ligt, Joep, Lameijer, Eric Wubbo, Van Dijk, Freerk, Hormozdiari, Fereydoun, Uitterlinden, André G., Van Duijn, Cornelia M., Eichler, Evan E., De Bakker, Paul I.W., Swertz, Morris A., Wijmenga, Cisca, Van Ommen, Gert Jan B, Slagboom, P. Eline, Boomsma, Dorret I., Schönhuth, Alexander, Ye, Kai, Guryev, Victor, Bovenberg, Jasper A., De Craen, Anton J M, Beekman, Marian, Hofman, Albert, Willemsen, Gonneke, Wolffenbuttel, Bruce, Platteel, Mathieu, Du, Yuanping, Chen, Ruoyan, Cao, Hongzhi, Cao, Rui, Sun, Yushen, Cao, Jeremy Sujie, Neerincx, Pieter B T, Dijkstra, Martijn, Byelas, George, Kanterakis, Alexandros, Bot, Jan, Vermaat, Martijn, Laros, Jeroen F., den Dunnen, Johan T., De Knijff, Peter, Karssen, Lennart C., Van Leeuwen, Elisa M., Amin, Najaf, Rivadeneira, Fernando, Estrada, Karol, Hottenga, Jouke-Jan, Kattenberg, V. Mathijs, Van Enckevort, David, Mei, Hailiang, Santcroos, Mark, Van Schaik, Barbera D C, Handsaker, Robert E., McCarroll, Steven A., Ko, Arthur, Sudmant, Peter, Nijman, Isaac J., Genetica, CMM Groep Kloosterman, Child Health, Cancer, CMM Groep Kaaij, CMM Groep Cuppen, CMM Groep De Ridder, Epi Methoden Team 2, Infection & Immunity, Circulatory Health, Hubrecht Institute with UMC, Genetica Medische Informatica, Genetica Sectie Genoomdiagnostiek, Hehir-Kwa, Jayne Y., Marschall, Tobias, Kloosterman, Wigard P., Francioli, Laurent C., Baaijens, Jasmijn A., Dijkstra, Louis J., Abdellaoui, Abdel, Koval, Vyacheslav, Thung, Djie Tjwan, Wardenaar, René, Renkens, Ivo, Coe, Bradley P., Deelen, Patrick, De Ligt, Joep, Lameijer, Eric Wubbo, Van Dijk, Freerk, Hormozdiari, Fereydoun, Uitterlinden, André G., Van Duijn, Cornelia M., Eichler, Evan E., De Bakker, Paul I.W., Swertz, Morris A., Wijmenga, Cisca, Van Ommen, Gert Jan B, Slagboom, P. Eline, Boomsma, Dorret I., Schönhuth, Alexander, Ye, Kai, Guryev, Victor, Bovenberg, Jasper A., De Craen, Anton J M, Beekman, Marian, Hofman, Albert, Willemsen, Gonneke, Wolffenbuttel, Bruce, Platteel, Mathieu, Du, Yuanping, Chen, Ruoyan, Cao, Hongzhi, Cao, Rui, Sun, Yushen, Cao, Jeremy Sujie, Neerincx, Pieter B T, Dijkstra, Martijn, Byelas, George, Kanterakis, Alexandros, Bot, Jan, Vermaat, Martijn, Laros, Jeroen F., den Dunnen, Johan T., De Knijff, Peter, Karssen, Lennart C., Van Leeuwen, Elisa M., Amin, Najaf, Rivadeneira, Fernando, Estrada, Karol, Hottenga, Jouke-Jan, Kattenberg, V. Mathijs, Van Enckevort, David, Mei, Hailiang, Santcroos, Mark, Van Schaik, Barbera D C, Handsaker, Robert E., McCarroll, Steven A., Ko, Arthur, Sudmant, Peter, and Nijman, Isaac J.

Published
2016

12. Transmission of human mtDNA heteroplasmy in the genome of the Netherlands families: Support for a variable-size bottleneck

Author

Epidemiology & Health Economics, CMM Groep Kaaij, Brain, Infection & Immunity, Circulatory Health, JC onderzoeksprogramma Methodologie, CMM Groep Cuppen, Cancer, CMM Groep Kloosterman, Child Health, Genetica Medische Informatica, Genetica Sectie Genoomdiagnostiek, Li, Mingkun, Rothwell, Rebecca, Vermaat, Martijn, Wachsmuth, Manja, Schröder, Roland, Laros, Jeroen F J, Van Oven, Mannis, De Bakker, Paul I W, Bovenberg, Jasper A., Van Duijn, Cornelia M., Van Ommen, Gert Jan B, Slagboom, P. Eline, Swertz, Morris A., Wijmenga, Cisca, Kayser, Manfred, Boomsma, Dorret I., Zöllner, Sebastian, De Knijff, Peter, Stoneking, Mark, De Craen, Anton J M, Beekman, Marian, Hofman, Albert, Willemsen, Gonneke, Wolffenbuttel, Bruce, Platteel, Mathieu, Du, Yuanping, Chen, Ruoyan, Cao, Hongzhi, Cao, Rui, Sun, Yushen, Cao, Jeremy Sujie, Van Dijk, Freerk, Neerincx, Pieter B T, Deelen, Patrick, Dijkstra, Martijn, Byelas, George, Kanterakis, Alexandros, Bot, Jan, Ye, Kai, Lameijer, Eric Wubbo, Den Dunnen, Johan T., Karssen, Lennart C., Van Leeuwen, Elisa M., Amin, Najaf, Koval, Vyacheslav, Rivadeneira, Fernando, Estrada, Karol, Hehir-Kwa, Jayne Y., De Ligt, Joep, Abdellaoui, Abdel, Hottenga, Jouke Jan, Kattenberg, V. Mathijs, Van Enckevort, David, Mei, Hailiang, Santcroos, Mark, Van Schaik, Barbera D C, Handsaker, Robert E., McCarroll, Steven A., Eichler, Evan E., Ko, Arthur, Sudmant, Peter, Francioli, Laurent C., Kloosterman, Wigard P., Nijman, Isaac J., Guryev, Victor, Epidemiology & Health Economics, CMM Groep Kaaij, Brain, Infection & Immunity, Circulatory Health, JC onderzoeksprogramma Methodologie, CMM Groep Cuppen, Cancer, CMM Groep Kloosterman, Child Health, Genetica Medische Informatica, Genetica Sectie Genoomdiagnostiek, Li, Mingkun, Rothwell, Rebecca, Vermaat, Martijn, Wachsmuth, Manja, Schröder, Roland, Laros, Jeroen F J, Van Oven, Mannis, De Bakker, Paul I W, Bovenberg, Jasper A., Van Duijn, Cornelia M., Van Ommen, Gert Jan B, Slagboom, P. Eline, Swertz, Morris A., Wijmenga, Cisca, Kayser, Manfred, Boomsma, Dorret I., Zöllner, Sebastian, De Knijff, Peter, Stoneking, Mark, De Craen, Anton J M, Beekman, Marian, Hofman, Albert, Willemsen, Gonneke, Wolffenbuttel, Bruce, Platteel, Mathieu, Du, Yuanping, Chen, Ruoyan, Cao, Hongzhi, Cao, Rui, Sun, Yushen, Cao, Jeremy Sujie, Van Dijk, Freerk, Neerincx, Pieter B T, Deelen, Patrick, Dijkstra, Martijn, Byelas, George, Kanterakis, Alexandros, Bot, Jan, Ye, Kai, Lameijer, Eric Wubbo, Den Dunnen, Johan T., Karssen, Lennart C., Van Leeuwen, Elisa M., Amin, Najaf, Koval, Vyacheslav, Rivadeneira, Fernando, Estrada, Karol, Hehir-Kwa, Jayne Y., De Ligt, Joep, Abdellaoui, Abdel, Hottenga, Jouke Jan, Kattenberg, V. Mathijs, Van Enckevort, David, Mei, Hailiang, Santcroos, Mark, Van Schaik, Barbera D C, Handsaker, Robert E., McCarroll, Steven A., Eichler, Evan E., Ko, Arthur, Sudmant, Peter, Francioli, Laurent C., Kloosterman, Wigard P., Nijman, Isaac J., and Guryev, Victor

Published
2016

13. Genome of the Netherlands population-specific imputations identify an ABCA6 variant associated with cholesterol levels

Author

Van Leeuwen, Elisabeth M., Karssen, Lennart C., Deelen, Joris, Isaacs, Aaron, Medina-Gomez, Carolina, Mbarek, Hamdi, Kanterakis, Alexandros, Trompet, Stella, Postmus, Iris, Verweij, Niek, Van Enckevort, David J., Huffman, Jennifer E., White, Charles C., Feitosa, Mary F., Bartz, Traci M., Manichaikul, Ani, Joshi, Peter K., Peloso, Gina M., Deelen, Patrick, Van Dijk, Freerk, Willemsen, Gonneke, De Geus, Eco J., Milaneschi, Yuri, Penninx, Brenda W J H, Francioli, Laurent C., Menelaou, Androniki, Pulit, Sara L., Rivadeneira, Fernando, Hofman, Albert, Oostra, Ben A., Franco, Oscar H., Leach, Irene Mateo, Beekman, Marian, De Craen, Anton J M, Uh, Hae Won, Trochet, Holly, Hocking, Lynne J., Porteous, David J., Sattar, Naveed, Packard, Chris J., Buckley, Brendan M., Brody, Jennifer A., Bis, Joshua C., Rotter, Jerome I., Mychaleckyj, Josyf C., Campbell, Harry, Duan, Qing, Lange, Leslie A., Wilson, James F., Hayward, Caroline, Polasek, Ozren, Vitart, Veronique, Rudan, Igor, Wright, Alan F., Rich, Stephen S., Psaty, Bruce M., Borecki, Ingrid B., Kearney, Patricia M., Stott, David J., Cupples, L. Adrienne, Jukema, J. Wouter, Van Der Harst, Pim, Sijbrands, Eric J., Hottenga, Jouke Jan, Uitterlinden, Andre G., Swertz, Morris A., Van Ommen, Gert Jan B, De Bakker, Paul I W, Eline Slagboom, P., Boomsma, Dorret I., Wijmenga, Cisca, Van Duijn, Cornelia M., Neerincx, Pieter B T, Elbers, Clara C., Palamara, Pier Francesco, Peer, Itsik, Abdellaoui, Abdel, Kloosterman, Wigard P., Van Oven, Mannis, Vermaat, Martijn, Li, Mingkun, Laros, Jeroen F J, Stoneking, Mark, De Knijff, Peter, Kayser, Manfred, Veldink, Jan H., Van Den Berg, Leonard H., Byelas, Heorhiy, Den Dunnen, Johan T., Dijkstra, Martijn, Amin, Najaf, Van Der Velde, K. Joeri, Van Setten, Jessica, Kattenberg, Mathijs, Van Schaik, Barbera D C, Bot, Jan, Nijman, Isaäc J., Mei, Hailiang, Koval, Vyacheslav, Ye, Kai, Lameijer, Eric Wubbo, Moed, Matthijs H., Hehir-Kwa, Jayne Y., Handsaker, Robert E., Sunyaev, Shamil R., Sohail, Mashaal, Hormozdiari, Fereydoun, Marschall, Tobias, Schönhuth, Alexander, Guryev, Victor, Suchiman, H. Eka D, Wolffenbuttel, Bruce H., Platteel, Mathieu, Pitts, Steven J., Potluri, Shobha, Cox, David R., Li, Qibin, Li, Yingrui, Du, Yuanping, Chen, Ruoyan, Cao, Hongzhi, Li, Ning, Cao, Sujie, Wang, Jun, Bovenberg, Jasper A., Van Leeuwen, Elisabeth M., Karssen, Lennart C., Deelen, Joris, Isaacs, Aaron, Medina-Gomez, Carolina, Mbarek, Hamdi, Kanterakis, Alexandros, Trompet, Stella, Postmus, Iris, Verweij, Niek, Van Enckevort, David J., Huffman, Jennifer E., White, Charles C., Feitosa, Mary F., Bartz, Traci M., Manichaikul, Ani, Joshi, Peter K., Peloso, Gina M., Deelen, Patrick, Van Dijk, Freerk, Willemsen, Gonneke, De Geus, Eco J., Milaneschi, Yuri, Penninx, Brenda W J H, Francioli, Laurent C., Menelaou, Androniki, Pulit, Sara L., Rivadeneira, Fernando, Hofman, Albert, Oostra, Ben A., Franco, Oscar H., Leach, Irene Mateo, Beekman, Marian, De Craen, Anton J M, Uh, Hae Won, Trochet, Holly, Hocking, Lynne J., Porteous, David J., Sattar, Naveed, Packard, Chris J., Buckley, Brendan M., Brody, Jennifer A., Bis, Joshua C., Rotter, Jerome I., Mychaleckyj, Josyf C., Campbell, Harry, Duan, Qing, Lange, Leslie A., Wilson, James F., Hayward, Caroline, Polasek, Ozren, Vitart, Veronique, Rudan, Igor, Wright, Alan F., Rich, Stephen S., Psaty, Bruce M., Borecki, Ingrid B., Kearney, Patricia M., Stott, David J., Cupples, L. Adrienne, Jukema, J. Wouter, Van Der Harst, Pim, Sijbrands, Eric J., Hottenga, Jouke Jan, Uitterlinden, Andre G., Swertz, Morris A., Van Ommen, Gert Jan B, De Bakker, Paul I W, Eline Slagboom, P., Boomsma, Dorret I., Wijmenga, Cisca, Van Duijn, Cornelia M., Neerincx, Pieter B T, Elbers, Clara C., Palamara, Pier Francesco, Peer, Itsik, Abdellaoui, Abdel, Kloosterman, Wigard P., Van Oven, Mannis, Vermaat, Martijn, Li, Mingkun, Laros, Jeroen F J, Stoneking, Mark, De Knijff, Peter, Kayser, Manfred, Veldink, Jan H., Van Den Berg, Leonard H., Byelas, Heorhiy, Den Dunnen, Johan T., Dijkstra, Martijn, Amin, Najaf, Van Der Velde, K. Joeri, Van Setten, Jessica, Kattenberg, Mathijs, Van Schaik, Barbera D C, Bot, Jan, Nijman, Isaäc J., Mei, Hailiang, Koval, Vyacheslav, Ye, Kai, Lameijer, Eric Wubbo, Moed, Matthijs H., Hehir-Kwa, Jayne Y., Handsaker, Robert E., Sunyaev, Shamil R., Sohail, Mashaal, Hormozdiari, Fereydoun, Marschall, Tobias, Schönhuth, Alexander, Guryev, Victor, Suchiman, H. Eka D, Wolffenbuttel, Bruce H., Platteel, Mathieu, Pitts, Steven J., Potluri, Shobha, Cox, David R., Li, Qibin, Li, Yingrui, Du, Yuanping, Chen, Ruoyan, Cao, Hongzhi, Li, Ning, Cao, Sujie, Wang, Jun, and Bovenberg, Jasper A.

Abstract

Variants associated with blood lipid levels may be population-specific. To identify low-frequency variants associated with this phenotype, population-specific reference panels may be used. Here we impute nine large Dutch biobanks (∼35,000 samples) with the population-specific reference panel created by the Genome of the Netherlands Project and perform association testing with blood lipid levels. We report the discovery of five novel associations at four loci (P value -4), including a rare missense variant in ABCA6 (rs77542162, p.Cys1359Arg, frequency 0.034), which is predicted to be deleterious. The frequency of this ABCA6 variant is 3.65-fold increased in the Dutch and its effect (βLDL-C =0.135, βTC =0.140) is estimated to be very similar to those observed for single variants in well-known lipid genes, such as LDLR.

Published
2015

14. Genome of the Netherlands population-specific imputations identify an ABCA6 variant associated with cholesterol levels

Author

CMM Groep Kaaij, CMM Groep Kloosterman, Child Health, Cancer, ZL Neuromusculaire Ziekten Medisch, Experimentele Afd. Cardiologie 1, CMM Groep Cuppen, JC onderzoeksprogramma Methodologie, Van Leeuwen, Elisabeth M., Karssen, Lennart C., Deelen, Joris, Isaacs, Aaron, Medina-Gomez, Carolina, Mbarek, Hamdi, Kanterakis, Alexandros, Trompet, Stella, Postmus, Iris, Verweij, Niek, Van Enckevort, David J., Huffman, Jennifer E., White, Charles C., Feitosa, Mary F., Bartz, Traci M., Manichaikul, Ani, Joshi, Peter K., Peloso, Gina M., Deelen, Patrick, Van Dijk, Freerk, Willemsen, Gonneke, De Geus, Eco J., Milaneschi, Yuri, Penninx, Brenda W J H, Francioli, Laurent C., Menelaou, Androniki, Pulit, Sara L., Rivadeneira, Fernando, Hofman, Albert, Oostra, Ben A., Franco, Oscar H., Leach, Irene Mateo, Beekman, Marian, De Craen, Anton J M, Uh, Hae Won, Trochet, Holly, Hocking, Lynne J., Porteous, David J., Sattar, Naveed, Packard, Chris J., Buckley, Brendan M., Brody, Jennifer A., Bis, Joshua C., Rotter, Jerome I., Mychaleckyj, Josyf C., Campbell, Harry, Duan, Qing, Lange, Leslie A., Wilson, James F., Hayward, Caroline, Polasek, Ozren, Vitart, Veronique, Rudan, Igor, Wright, Alan F., Rich, Stephen S., Psaty, Bruce M., Borecki, Ingrid B., Kearney, Patricia M., Stott, David J., Cupples, L. Adrienne, Jukema, J. Wouter, Van Der Harst, Pim, Sijbrands, Eric J., Hottenga, Jouke Jan, Uitterlinden, Andre G., Swertz, Morris A., Van Ommen, Gert Jan B, De Bakker, Paul I W, Eline Slagboom, P., Boomsma, Dorret I., Wijmenga, Cisca, Van Duijn, Cornelia M., Neerincx, Pieter B T, Elbers, Clara C., Palamara, Pier Francesco, Peer, Itsik, Abdellaoui, Abdel, Kloosterman, Wigard P., Van Oven, Mannis, Vermaat, Martijn, Li, Mingkun, Laros, Jeroen F J, Stoneking, Mark, De Knijff, Peter, Kayser, Manfred, Veldink, Jan H., Van Den Berg, Leonard H., Byelas, Heorhiy, Den Dunnen, Johan T., Dijkstra, Martijn, Amin, Najaf, Van Der Velde, K. Joeri, Van Setten, Jessica, Kattenberg, Mathijs, Van Schaik, Barbera D C, Bot, Jan, Nijman, Isaäc J., Mei, Hailiang, Koval, Vyacheslav, Ye, Kai, Lameijer, Eric Wubbo, Moed, Matthijs H., Hehir-Kwa, Jayne Y., Handsaker, Robert E., Sunyaev, Shamil R., Sohail, Mashaal, Hormozdiari, Fereydoun, Marschall, Tobias, Schönhuth, Alexander, Guryev, Victor, Suchiman, H. Eka D, Wolffenbuttel, Bruce H., Platteel, Mathieu, Pitts, Steven J., Potluri, Shobha, Cox, David R., Li, Qibin, Li, Yingrui, Du, Yuanping, Chen, Ruoyan, Cao, Hongzhi, Li, Ning, Cao, Sujie, Wang, Jun, Bovenberg, Jasper A., de Bakker, Paul I W, CMM Groep Kaaij, CMM Groep Kloosterman, Child Health, Cancer, ZL Neuromusculaire Ziekten Medisch, Experimentele Afd. Cardiologie 1, CMM Groep Cuppen, JC onderzoeksprogramma Methodologie, Van Leeuwen, Elisabeth M., Karssen, Lennart C., Deelen, Joris, Isaacs, Aaron, Medina-Gomez, Carolina, Mbarek, Hamdi, Kanterakis, Alexandros, Trompet, Stella, Postmus, Iris, Verweij, Niek, Van Enckevort, David J., Huffman, Jennifer E., White, Charles C., Feitosa, Mary F., Bartz, Traci M., Manichaikul, Ani, Joshi, Peter K., Peloso, Gina M., Deelen, Patrick, Van Dijk, Freerk, Willemsen, Gonneke, De Geus, Eco J., Milaneschi, Yuri, Penninx, Brenda W J H, Francioli, Laurent C., Menelaou, Androniki, Pulit, Sara L., Rivadeneira, Fernando, Hofman, Albert, Oostra, Ben A., Franco, Oscar H., Leach, Irene Mateo, Beekman, Marian, De Craen, Anton J M, Uh, Hae Won, Trochet, Holly, Hocking, Lynne J., Porteous, David J., Sattar, Naveed, Packard, Chris J., Buckley, Brendan M., Brody, Jennifer A., Bis, Joshua C., Rotter, Jerome I., Mychaleckyj, Josyf C., Campbell, Harry, Duan, Qing, Lange, Leslie A., Wilson, James F., Hayward, Caroline, Polasek, Ozren, Vitart, Veronique, Rudan, Igor, Wright, Alan F., Rich, Stephen S., Psaty, Bruce M., Borecki, Ingrid B., Kearney, Patricia M., Stott, David J., Cupples, L. Adrienne, Jukema, J. Wouter, Van Der Harst, Pim, Sijbrands, Eric J., Hottenga, Jouke Jan, Uitterlinden, Andre G., Swertz, Morris A., Van Ommen, Gert Jan B, De Bakker, Paul I W, Eline Slagboom, P., Boomsma, Dorret I., Wijmenga, Cisca, Van Duijn, Cornelia M., Neerincx, Pieter B T, Elbers, Clara C., Palamara, Pier Francesco, Peer, Itsik, Abdellaoui, Abdel, Kloosterman, Wigard P., Van Oven, Mannis, Vermaat, Martijn, Li, Mingkun, Laros, Jeroen F J, Stoneking, Mark, De Knijff, Peter, Kayser, Manfred, Veldink, Jan H., Van Den Berg, Leonard H., Byelas, Heorhiy, Den Dunnen, Johan T., Dijkstra, Martijn, Amin, Najaf, Van Der Velde, K. Joeri, Van Setten, Jessica, Kattenberg, Mathijs, Van Schaik, Barbera D C, Bot, Jan, Nijman, Isaäc J., Mei, Hailiang, Koval, Vyacheslav, Ye, Kai, Lameijer, Eric Wubbo, Moed, Matthijs H., Hehir-Kwa, Jayne Y., Handsaker, Robert E., Sunyaev, Shamil R., Sohail, Mashaal, Hormozdiari, Fereydoun, Marschall, Tobias, Schönhuth, Alexander, Guryev, Victor, Suchiman, H. Eka D, Wolffenbuttel, Bruce H., Platteel, Mathieu, Pitts, Steven J., Potluri, Shobha, Cox, David R., Li, Qibin, Li, Yingrui, Du, Yuanping, Chen, Ruoyan, Cao, Hongzhi, Li, Ning, Cao, Sujie, Wang, Jun, Bovenberg, Jasper A., and de Bakker, Paul I W

Published
2015

15. Characteristics of de novo structural changes in the human genome

Author

CMM Groep Kloosterman, Child Health, Cancer, Genetica, CMM Sectie Genomics and Bioinformatics, Hubrecht Institute with UMC, JC onderzoeksprogramma Methodologie, Epi Methoden Team 1, Kloosterman, Wigard P., Francioli, Laurent C., Hormozdiari, Fereydoun, Marschall, Tobias, Hehir-Kwa, Jayne Y., Abdellaoui, Abdel, Lameijer, Eric Wubbo, Moed, Matthijs H., Koval, Vyacheslav, Renkens, Ivo, Van Roosmalen, Markus J., Arp, Pascal, Karssen, Lennart C., Coe, Bradley P., Handsaker, Robert E., Suchiman, Eka D., Cuppen, Edwin, Thung, Djie Tjwan, McVey, Mitch, Wendl, Michael C., Uitterlinden, André, Van Duijn, Cornelia M., Swertz, Morris A., Wijmenga, Cisca, Van Ommen, Gert Jan B, Slagboom, P. Eline, Boomsma, Dorret I., Schönhuth, Alexander, Eichler, Evan E., De Bakker, Paul I W, Ye, Kai, Guryev, Victor, Bovenberg, Jasper A., De Craen, Anton J M, Beekman, Marian, Hofman, Albert, Willemsen, Gonneke, Wolffenbuttel, Bruce, Platteel, Mathieu, Du, Yuanping, Chen, Ruoyan, Cao, Hongzhi, Cao, Rui, Sun, Yushen, Cao, Jeremy Sujie, Van Dijk, Freerk, Neerincx, Pieter B T, Deelen, Patrick, Dijkstra, Martijn, Byelas, George, Kanterakis, Alexandros, Bot, Jan, Vermaat, Martijn, Laros, Jeroen F J, Den Dunnen, Johan T., De Knijff, Peter, Van Leeuwen, Elisa M., Amin, Najaf, Rivadeneira, Fernando, Estrada, Karol, De Ligt, Joep, Hottenga, Jouke Jan, Kattenberg, V. Mathijs, Van Enckevort, David, Mei, Hailiang, Santcroos, Mark, Van Schaik, Barbera D C, McCarroll, Steven A., Ko, Arthur, Sudmant, Peter, Nijman, Isaac J., CMM Groep Kloosterman, Child Health, Cancer, Genetica, CMM Sectie Genomics and Bioinformatics, Hubrecht Institute with UMC, JC onderzoeksprogramma Methodologie, Epi Methoden Team 1, Kloosterman, Wigard P., Francioli, Laurent C., Hormozdiari, Fereydoun, Marschall, Tobias, Hehir-Kwa, Jayne Y., Abdellaoui, Abdel, Lameijer, Eric Wubbo, Moed, Matthijs H., Koval, Vyacheslav, Renkens, Ivo, Van Roosmalen, Markus J., Arp, Pascal, Karssen, Lennart C., Coe, Bradley P., Handsaker, Robert E., Suchiman, Eka D., Cuppen, Edwin, Thung, Djie Tjwan, McVey, Mitch, Wendl, Michael C., Uitterlinden, André, Van Duijn, Cornelia M., Swertz, Morris A., Wijmenga, Cisca, Van Ommen, Gert Jan B, Slagboom, P. Eline, Boomsma, Dorret I., Schönhuth, Alexander, Eichler, Evan E., De Bakker, Paul I W, Ye, Kai, Guryev, Victor, Bovenberg, Jasper A., De Craen, Anton J M, Beekman, Marian, Hofman, Albert, Willemsen, Gonneke, Wolffenbuttel, Bruce, Platteel, Mathieu, Du, Yuanping, Chen, Ruoyan, Cao, Hongzhi, Cao, Rui, Sun, Yushen, Cao, Jeremy Sujie, Van Dijk, Freerk, Neerincx, Pieter B T, Deelen, Patrick, Dijkstra, Martijn, Byelas, George, Kanterakis, Alexandros, Bot, Jan, Vermaat, Martijn, Laros, Jeroen F J, Den Dunnen, Johan T., De Knijff, Peter, Van Leeuwen, Elisa M., Amin, Najaf, Rivadeneira, Fernando, Estrada, Karol, De Ligt, Joep, Hottenga, Jouke Jan, Kattenberg, V. Mathijs, Van Enckevort, David, Mei, Hailiang, Santcroos, Mark, Van Schaik, Barbera D C, McCarroll, Steven A., Ko, Arthur, Sudmant, Peter, and Nijman, Isaac J.

Published
2015

16. The Genome of the Netherlands:design, and project goals

Author

Boomsma, Dorret I., Wijmenga, Cisca, Slagboom, Eline P., Swertz, Morris A., Karssen, Lennart C., Abdellaoui, Abdel, Ye, Kai, Guryev, Victor, Vermaat, Martijn, van Dijk, Freerk, Francioli, Laurent C., Hottenga, Jouke Jan, Laros, Jeroen F. J., Li, Qibin, Li, Yingrui, Cao, Hongzhi, Chen, Ruoyan, Du, Yuanping, Li, Ning, Cao, Sujie, van Setten, Jessica, Menelaou, Androniki, Pulit, Sara L., Hehir-Kwa, Jayne Y., Beekman, Marian, Elbers, Clara C., Byelas, Heorhiy, de Craen, Anton J. M., Deelen, Patrick, Dijkstra, Martijn, den Dunnen, Johan T., de Knijff, Peter, Houwing-Duistermaat, Jeanine, Koval, Vyacheslav, Estrada, Karol, Hofman, Albert, Kanterakis, Alexandros, van Enckevort, David, Mai, Hailiang, Kattenberg, Mathijs, van Leeuwen, Elisabeth M., Neerincx, Pieter B. T., Oostra, Ben, Rivadeneira, Fernanodo, Suchiman, Eka H. D., Uitterlinden, Andre G., Willemsen, Gonneke, Wolffenbuttel, Bruce H., Wang, Jun, de Bakker, Paul I. W., van Ommen, Gert-Jan, van Duijn, Cornelia M., Boomsma, Dorret I., Wijmenga, Cisca, Slagboom, Eline P., Swertz, Morris A., Karssen, Lennart C., Abdellaoui, Abdel, Ye, Kai, Guryev, Victor, Vermaat, Martijn, van Dijk, Freerk, Francioli, Laurent C., Hottenga, Jouke Jan, Laros, Jeroen F. J., Li, Qibin, Li, Yingrui, Cao, Hongzhi, Chen, Ruoyan, Du, Yuanping, Li, Ning, Cao, Sujie, van Setten, Jessica, Menelaou, Androniki, Pulit, Sara L., Hehir-Kwa, Jayne Y., Beekman, Marian, Elbers, Clara C., Byelas, Heorhiy, de Craen, Anton J. M., Deelen, Patrick, Dijkstra, Martijn, den Dunnen, Johan T., de Knijff, Peter, Houwing-Duistermaat, Jeanine, Koval, Vyacheslav, Estrada, Karol, Hofman, Albert, Kanterakis, Alexandros, van Enckevort, David, Mai, Hailiang, Kattenberg, Mathijs, van Leeuwen, Elisabeth M., Neerincx, Pieter B. T., Oostra, Ben, Rivadeneira, Fernanodo, Suchiman, Eka H. D., Uitterlinden, Andre G., Willemsen, Gonneke, Wolffenbuttel, Bruce H., Wang, Jun, de Bakker, Paul I. W., van Ommen, Gert-Jan, and van Duijn, Cornelia M.

Published
2014

17. Whole-genome sequence variation, population structure and demographic history of the Dutch population

Author

Francioli, Laurent C., Menelaou, Andronild, Pulit, Sara L., Van Dijk, Freerk, Palamara, Pier Francesco, Elbers, Clara C., Neerincx, Pieter B. T., Ye, Kai, Guryev, Victor, Kloosterman, Wigard P., Deelen, Patrick, Abdellaoui, Abdel, Van Leeuwen, Elisabeth M., Van Oven, Mannis, Vermaat, Martijn, Li, Mingkun, Laros, Jeroen F. J., Karssen, Lennart C., Kanterakis, Alexandros, Amin, Najaf, Hottenga, Jouke Jan, Lameijer, Eric-Wubbo, Kattenberg, Mathijs, Dijkstra, Martijn, Byelas, Heorhiy, Van Settenl, Jessica, Van Schaik, Barbera D. C., Bot, Jan, Nijman, Isaac J., Renkens, Ivo, Marscha, Tobias, Schonhuth, Alexander, Hehir-Kwa, Jayne Y., Handsaker, Robert E., Polak, Paz, Sohail, Mashaal, Vuzman, Dana, Hormozdiari, Fereydoun, Van Enckevort, David, Mei, Hailiang, Koval, Vyacheslav, Moed, Ma-Tthijs H., Van der Velde, K. Joeri, Rivadeneira, Fernando, Estrada, Karol, Medina-Gomez, Carolina, Isaacs, Aaron, McCarroll, Steven A., Beekrnan, Marian, De Craen, Anton J. M., Suchiman, H. Eka D., Hofman, Albert, Oostra, Ben, Uitterlinden, Andre G., Willemsen, Gonneke, Plattee, Mathieu, Veldink, Jan H., Van den Berg, Leonard H., Pitts, Steven J., Potluri, Shobha, Sundar, Purnima, Cox, David R., Sunyaev, Shamil R., Den Dunnen, Johan T., Stoneking, Mark, De Knijff, Peter, Kayser, Manfred, Li, Qibin, Li, Yingrui, Du, Yuanping, Chen, Ruoyan, Cao, Hongzhi, Li, Ning, Cao, Sujie, Wang, Jun, Bovenberg, Jasper A., Peer, Itsik, Slagboom, P. Eline, Van Duijn, Cornelia M., Boomsma, Dorret I., Van Ommen, Gert-Jan B., De Bakker, Paul I. W., Swertz, Morris A., Wijmenga, Cisca, Francioli, Laurent C., Menelaou, Andronild, Pulit, Sara L., Van Dijk, Freerk, Palamara, Pier Francesco, Elbers, Clara C., Neerincx, Pieter B. T., Ye, Kai, Guryev, Victor, Kloosterman, Wigard P., Deelen, Patrick, Abdellaoui, Abdel, Van Leeuwen, Elisabeth M., Van Oven, Mannis, Vermaat, Martijn, Li, Mingkun, Laros, Jeroen F. J., Karssen, Lennart C., Kanterakis, Alexandros, Amin, Najaf, Hottenga, Jouke Jan, Lameijer, Eric-Wubbo, Kattenberg, Mathijs, Dijkstra, Martijn, Byelas, Heorhiy, Van Settenl, Jessica, Van Schaik, Barbera D. C., Bot, Jan, Nijman, Isaac J., Renkens, Ivo, Marscha, Tobias, Schonhuth, Alexander, Hehir-Kwa, Jayne Y., Handsaker, Robert E., Polak, Paz, Sohail, Mashaal, Vuzman, Dana, Hormozdiari, Fereydoun, Van Enckevort, David, Mei, Hailiang, Koval, Vyacheslav, Moed, Ma-Tthijs H., Van der Velde, K. Joeri, Rivadeneira, Fernando, Estrada, Karol, Medina-Gomez, Carolina, Isaacs, Aaron, McCarroll, Steven A., Beekrnan, Marian, De Craen, Anton J. M., Suchiman, H. Eka D., Hofman, Albert, Oostra, Ben, Uitterlinden, Andre G., Willemsen, Gonneke, Plattee, Mathieu, Veldink, Jan H., Van den Berg, Leonard H., Pitts, Steven J., Potluri, Shobha, Sundar, Purnima, Cox, David R., Sunyaev, Shamil R., Den Dunnen, Johan T., Stoneking, Mark, De Knijff, Peter, Kayser, Manfred, Li, Qibin, Li, Yingrui, Du, Yuanping, Chen, Ruoyan, Cao, Hongzhi, Li, Ning, Cao, Sujie, Wang, Jun, Bovenberg, Jasper A., Peer, Itsik, Slagboom, P. Eline, Van Duijn, Cornelia M., Boomsma, Dorret I., Van Ommen, Gert-Jan B., De Bakker, Paul I. W., Swertz, Morris A., and Wijmenga, Cisca

Published
2014

18. Long range percolation on the hierarchical lattice

Author

Koval, Vyacheslav, Meester, Ronald, Trapman, Pieter, Koval, Vyacheslav, Meester, Ronald, and Trapman, Pieter

Abstract

We study long-range percolation on the hierarchical lattice of order N, where any edge of length k is present with probability p(k) = 1 - exp (-beta(-k)alpha), independently of all other edges. For fixed beta, we show that alpha(c)(beta) ( the infimum of those alpha for which an infinite cluster exists a.s.) is non-trivial if and only if N < beta < N-2. Furthermore, we show uniqueness of the infinite component and continuity of the percolation probability and of alpha(c)(beta) as a function of beta. This means that the phase diagram of this model is well understood., AuthorCount:3

Published
2012
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19. The experience of social adaptation problem solving in the Donbass region of Ukraine

Author

Ivanov, Sergei, Koval, Vyacheslav, and Lyakh, Alexander

Subjects
ddc:330
Abstract

Old industrial regions such as Donbass region in Ukraine, require intensive restructurization to facilitate them full participation in the economic life of the country on equal rights as other regions of Ukraine as well as to ensure proper life conditions to the inhabitants of these regions, in which huge part of the country's population concentrate. Now this problem is solving mostly by means of technical closing of unprofitable enterprises. Especially it concerns the coal mine industry. This is a right way assuming that exists a real program of restructuring which includes not only the main steps of it but also the evaluation of all the process along with estimation of social transition cost. But because of absence of a sober policy in this process and poor information dissemination the government gets into a much more complicated problem - the growth of social unprotection, unsettleness and pauperization of a huge layer of the active able-bodied population. Such social cost of ungrounded restructurization is difficult to be accepted in modern state. In order to facilitate process of adaptation of population to new conditions the International Renaissance Foundation with Polish partners have jointly launched a project aimed at the development and dissemination of a strategy and methods of economic and social problems solving which connected to the process of restructurization of old industrial regions in countries in transition. The main topics of the project: - Regional community member's awareness. - General education, training the present and future managerial cadre, re-qualification and socio-professional reconversion. - Role of information in the process of restructurization. - Transformation the old and setting up new enterprises. - Creation and improvement of the instruments and the institutions of regional restructurization. - Conducting a forum of public dialogue. There are steps that have been already done on the way of project implementation: - Quantitative investigations - sociological analysis of four sites in Donetsk region mostly populated with coal miner's families. - Qualitative investigations on the above mentioned topics. - Three workshops conducted in Donetsk region (sities of Donetsk, Mekeevka and Stakhanov). - One workshop conducted in Gliwice (Poland). All the workshops were dedicated to investigation of the approaches to the creation of a decision making strategy which would help to solve problems of industrial restructurization, rebuilding of country's economy, and economic and social consequences of this processes. Along with the project implementation there have been established the Agency for Regional Development in Donetsk as an institution that is aimed to help the economic reforms promotion and practical implementation of the steps on structural rebuilding in the Donetsk region. In addition, two centers for Social Adaptation of Coal Miners were set in the sites of closed coal mines in Donetsk with the help of the International Renaissance Foundation. The future development of this project assumes to widen the circle of its participants including representatives from Nord-Rhein Westphalen (Germany) and Nord-Pas-de-Calais (France). The overall objective of the new phase of it is to use the combined experience of the project partners in order to develop and implement strategies which effectively address the economic problems caused by the decline in the coal mine industry. Key words: restructurization, social adaptation, decision making strategy.

Published
1998

20. The Genome of the Netherlands: design, and project goals

Author

Boomsma, Dorret I, primary, Wijmenga, Cisca, additional, Slagboom, Eline P, additional, Swertz, Morris A, additional, Karssen, Lennart C, additional, Abdellaoui, Abdel, additional, Ye, Kai, additional, Guryev, Victor, additional, Vermaat, Martijn, additional, van Dijk, Freerk, additional, Francioli, Laurent C, additional, Hottenga, Jouke Jan, additional, Laros, Jeroen F J, additional, Li, Qibin, additional, Li, Yingrui, additional, Cao, Hongzhi, additional, Chen, Ruoyan, additional, Du, Yuanping, additional, Li, Ning, additional, Cao, Sujie, additional, van Setten, Jessica, additional, Menelaou, Androniki, additional, Pulit, Sara L, additional, Hehir-Kwa, Jayne Y, additional, Beekman, Marian, additional, Elbers, Clara C, additional, Byelas, Heorhiy, additional, de Craen, Anton J M, additional, Deelen, Patrick, additional, Dijkstra, Martijn, additional, den Dunnen, Johan T, additional, de Knijff, Peter, additional, Houwing-Duistermaat, Jeanine, additional, Koval, Vyacheslav, additional, Estrada, Karol, additional, Hofman, Albert, additional, Kanterakis, Alexandros, additional, Enckevort, David van, additional, Mai, Hailiang, additional, Kattenberg, Mathijs, additional, van Leeuwen, Elisabeth M, additional, Neerincx, Pieter B T, additional, Oostra, Ben, additional, Rivadeneira, Fernanodo, additional, Suchiman, Eka H D, additional, Uitterlinden, Andre G, additional, Willemsen, Gonneke, additional, Wolffenbuttel, Bruce H, additional, Wang, Jun, additional, de Bakker, Paul I W, additional, van Ommen, Gert-Jan, additional, and van Duijn, Cornelia M, additional

Published
2013
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23. A framework for the detection of de novo mutations in family-based sequencing data

Author

Francioli, Laurent C, Cretu-Stancu, Mircea, Garimella, Kiran V, Fromer, Menachem, Kloosterman, Wigard P, Wijmenga, Cisca, Investigator, Principal, Swertz, Morris A, van Duijn, Cornelia M, Boomsma, Dorret I, Slagboom, PEline, van Ommen, Gertjan B, de Bakker, Paul IW, van Dijk, Freerk, Menelaou, Androniki, Neerincx, Pieter BT, Pulit, Sara L, Deelen, Patrick, Elbers, Clara C, Francesco Palamara, Pier, Pe'er, Itsik, Abdellaoui, Abdel, van Oven, Mannis, Vermaat, Martijn, Li, Mingkun, Laros, Jeroen FJ, Stoneking, Mark, de Knijff, Peter, Kayser, Manfred, Veldink, Jan H, van den Berg, Leonard H, Byelas, Heorhiy, den Dunnen, Johan T, Dijkstra, Martijn, Amin, Najaf, van der Velde, K Joeri, Hottenga, Jouke Jan, van Setten, Jessica, van Leeuwen, Elisabeth M, Kanterakis, Alexandros, Kattenberg, Mathijs, Karssen, Lennart C, van Schaik, Barbera DC, Bot, Jan, Nijman, Isaäc J, Renkens, Ivo, van Enckevort, David, Mei, Hailiang, Koval, Vyacheslav, Estrada, Karol, Medina-Gomez, Carolina, Ye, Kai, Lameijer, Eric-Wubbo, Moed, Matthijs H, Hehir-Kwa, Jayne Y, Handsaker, Robert E, McCarroll, Steven A, Sunyaev, Shamil R, Polak, Paz, Vuzman, Dana, Sohail, Mashaal, Hormozdiari, Fereydoun, Marschall, Tobias, Schönhuth, Alexander, Guryev, Victor, Slagboom, P Eline, Beekman, Marian B, de Craen, Anton JM, Suchiman, H Eka D, Hofman, Albert, Oostra, Ben, Isaacs, Aaron, Rivadeneira, Fernando, Uitterlinden, André G, Willemsen, Gonneke, Platteel, Mathieu, Pitts, Steven J, Potluri, Shobha, Sundar, Purnima, Cox, David R, Li, Qibin, Li, Yingrui, Du, Yuanping, Chen, Ruoyan, Cao, Hongzhi, Li, Ning, Cao, Sujie, Wang, Jun, Bovenberg, Jasper A, Brandsma, Margreet, Samocha, Kaitlin E, Neale, Benjamin M, Daly, Mark J, Banks, Eric, and DePristo, Mark A

Abstract

Germline mutation detection from human DNA sequence data is challenging due to the rarity of such events relative to the intrinsic error rates of sequencing technologies and the uneven coverage across the genome. We developed PhaseByTransmission (PBT) to identify de novo single nucleotide variants and short insertions and deletions (indels) from sequence data collected in parent-offspring trios. We compute the joint probability of the data given the genotype likelihoods in the individual family members, the known familial relationships and a prior probability for the mutation rate. Candidate de novo mutations (DNMs) are reported along with their posterior probability, providing a systematic way to prioritize them for validation. Our tool is integrated in the Genome Analysis Toolkit and can be used together with the ReadBackedPhasing module to infer the parental origin of DNMs based on phase-informative reads. Using simulated data, we show that PBT outperforms existing tools, especially in low coverage data and on the X chromosome. We further show that PBT displays high validation rates on empirical parent-offspring sequencing data for whole-exome data from 104 trios and X-chromosome data from 249 parent-offspring families. Finally, we demonstrate an association between father's age at conception and the number of DNMs in female offspring's X chromosome, consistent with previous literature reports.

Published
2016
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24. On classification of singular measures and fractal properties of quasi-self-affine measures in R2.

Author

Albeverio, Sergio, Koval, Vyacheslav, Pratsiovytyi, Mykola, and Torbin, G.

Subjects
*PROBABILITY theory, *REAL numbers, *HAUSDORFF measures, *MEASURE theory, *MATHEMATICAL transformations, *FRACTALS
Abstract

A multidimensional classification of singularly continuous (w.r.t. the Lebesgue measure) probability measures in R2 is introduced and a theorem on canonical representation of such measures is proven. A class of random elements on the unit square which is defined by a system of partitions generated by the Q*-representation of real numbers is introduced and studied in details. Conditions for the discreteness, absolute continuity resp. singular continuity (w.r.t. Lebesgue measure) of the corresponding probability measures are found. Metric, topological and fractal properties of the spectra of the corresponding probability distributions are investigated. A class of transformations preserving the Hausdorff-Besicovitch dimension of any subset of the unit square (DP-transformations) is also studied. [ABSTRACT FROM AUTHOR]

Published
2008
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25. On classification of singular measures and fractal properties of quasi-self-affine measures in R2.

Author

Albeverio, Sergio, Koval, Vyacheslav, Pratsiovytyi, Mykola, and Torbin, G.

Subjects
PROBABILITY theory, REAL numbers, HAUSDORFF measures, MEASURE theory, MATHEMATICAL transformations, FRACTALS
Abstract

A multidimensional classification of singularly continuous (w.r.t. the Lebesgue measure) probability measures in R2 is introduced and a theorem on canonical representation of such measures is proven. A class of random elements on the unit square which is defined by a system of partitions generated by the Q*-representation of real numbers is introduced and studied in details. Conditions for the discreteness, absolute continuity resp. singular continuity (w.r.t. Lebesgue measure) of the corresponding probability measures are found. Metric, topological and fractal properties of the spectra of the corresponding probability distributions are investigated. A class of transformations preserving the Hausdorff-Besicovitch dimension of any subset of the unit square (DP-transformations) is also studied. [ABSTRACT FROM AUTHOR]

Published
2008
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26. Improved imputation quality of low-frequency and rare variants in European samples using the ‘Genome of The Netherlands'

Author

Deelen, Patrick, Menelaou, Androniki, van Leeuwen, Elisabeth M, Kanterakis, Alexandros, van Dijk, Freerk, Medina-Gomez, Carolina, Francioli, Laurent C, Hottenga, Jouke Jan, Karssen, Lennart C, Estrada, Karol, Kreiner-Møller, Eskil, Rivadeneira, Fernando, van Setten, Jessica, Gutierrez-Achury, Javier, Westra, Harm-Jan, Franke, Lude, van Enckevort, David, Dijkstra, Martijn, Byelas, Heorhiy, van Duijn, Cornelia M, Swertz, Morris A, Neerincx, Pieter B T, Pulit, Sara L, Elbers, Clara C, Francesco Palamara, Pier, Pe'er, Itsik, Abdellaoui, Abdel, Kloosterman, Wigard P, van Oven, Mannis, Vermaat, Martijn, Li, Mingkun, Laros, Jeroen F J, Stoneking, Mark, de Knijff, Peter, Kayser, Manfred, Veldink, Jan H, van den Berg, Leonard H, den Dunnen, Johan T, Amin, Najaf, van der Velde, K Joeri, Jan Hottenga, Jouke, Kattenberg, Mathijs, van Schaik, Barbera D C, Bot, Jan, Nijman, Isaäuc J, Mei, Hailiang, Koval, Vyacheslav, Ye, Kai, Lameijer, Eric-Wubbo, Moed, Matthijs H, Hehir-Kwa, Jayne Y, Handsaker, Robert E, Sunyaev, Shamil R, Sohail, Mashaal, Hormozdiari, Fereydoun, Marschall, Tobias, Marschall, Schönhuth, Guryev, Victor, de Bakker, Paul I W, Slagboom, P Eline, Beekman, Marian B, de Craen, Anton J M, Suchiman, H Eka D, Hofman, Albert, van Duijn, Cornelia, Boomsma, Dorret I, Willemsen, Gonneke, Wolffenbuttel, Bruce H, Platteel, Mathieu, Pitts, Steven J, Potluri, Shobha, Cox, David R, Li, Qibin, Li, Yingrui, Du, Yuanping, Chen, Ruoyan, Cao, Hongzhi, Li, Ning, Cao, Sujie, Wang, Jun, Bovenberg, Jasper A, committee, Steering, Wijmenga, Cisca, and van Ommen, Gertjan B

Subjects
genotype imputation, GWAS, GoNL, rare variants, reference sets, reference panel
Abstract

Although genome-wide association studies (GWAS) have identified many common variants associated with complex traits, low-frequency and rare variants have not been interrogated in a comprehensive manner. Imputation from dense reference panels, such as the 1000 Genomes Project (1000G), enables testing of ungenotyped variants for association. Here we present the results of imputation using a large, new population-specific panel: the Genome of The Netherlands (GoNL). We benchmarked the performance of the 1000G and GoNL reference sets by comparing imputation genotypes with ‘true' genotypes typed on ImmunoChip in three European populations (Dutch, British, and Italian). GoNL showed significant improvement in the imputation quality for rare variants (MAF 0.05–0.5%) compared with 1000G. In Dutch samples, the mean observed Pearson correlation, r2, increased from 0.61 to 0.71. We also saw improved imputation accuracy for other European populations (in the British samples, r2 improved from 0.58 to 0.65, and in the Italians from 0.43 to 0.47). A combined reference set comprising 1000G and GoNL improved the imputation of rare variants even further. The Italian samples benefitted the most from this combined reference (the mean r2 increased from 0.47 to 0.50). We conclude that the creation of a large population-specific reference is advantageous for imputing rare variants and that a combined reference panel across multiple populations yields the best imputation results.

Published
2014
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27. The Genome of the Netherlands: design, and project goals.

Author

Boomsma DI, Wijmenga C, Slagboom EP, Swertz MA, Karssen LC, Abdellaoui A, Ye K, Guryev V, Vermaat M, van Dijk F, Francioli LC, Hottenga JJ, Laros JF, Li Q, Li Y, Cao H, Chen R, Du Y, Li N, Cao S, van Setten J, Menelaou A, Pulit SL, Hehir-Kwa JY, Beekman M, Elbers CC, Byelas H, de Craen AJ, Deelen P, Dijkstra M, den Dunnen JT, de Knijff P, Houwing-Duistermaat J, Koval V, Estrada K, Hofman A, Kanterakis A, Enckevort Dv, Mai H, Kattenberg M, van Leeuwen EM, Neerincx PB, Oostra B, Rivadeneira F, Suchiman EH, Uitterlinden AG, Willemsen G, Wolffenbuttel BH, Wang J, de Bakker PI, van Ommen GJ, and van Duijn CM

Subjects
Adult, Aged, Aged, 80 and over, Databases, Genetic, Female, Gene Frequency, High-Throughput Nucleotide Sequencing, Humans, Male, Middle Aged, Netherlands, Phylogeography, Sequence Analysis, DNA, Young Adult, Genetic Variation, Genome, Human
Abstract

Within the Netherlands a national network of biobanks has been established (Biobanking and Biomolecular Research Infrastructure-Netherlands (BBMRI-NL)) as a national node of the European BBMRI. One of the aims of BBMRI-NL is to enrich biobanks with different types of molecular and phenotype data. Here, we describe the Genome of the Netherlands (GoNL), one of the projects within BBMRI-NL. GoNL is a whole-genome-sequencing project in a representative sample consisting of 250 trio-families from all provinces in the Netherlands, which aims to characterize DNA sequence variation in the Dutch population. The parent-offspring trios include adult individuals ranging in age from 19 to 87 years (mean=53 years; SD=16 years) from birth cohorts 1910-1994. Sequencing was done on blood-derived DNA from uncultured cells and accomplished coverage was 14-15x. The family-based design represents a unique resource to assess the frequency of regional variants, accurately reconstruct haplotypes by family-based phasing, characterize short indels and complex structural variants, and establish the rate of de novo mutational events. GoNL will also serve as a reference panel for imputation in the available genome-wide association studies in Dutch and other cohorts to refine association signals and uncover population-specific variants. GoNL will create a catalog of human genetic variation in this sample that is uniquely characterized with respect to micro-geographic location and a wide range of phenotypes. The resource will be made available to the research and medical community to guide the interpretation of sequencing projects. The present paper summarizes the global characteristics of the project.

Published
2014
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