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1. A DNA Algorithm for Calculating the Maximum Flow of a Network

Author

Sackmann Andrea, Brown Kristelle, Formanowicz Piotr, Morgan Kevin, Kalsheker Noor, Garibaldi Jon M., and Błażewicz Jacek

Subjects
dna computing, network problems, max-flow, min-cut, Electronic computers. Computer science, QA75.5-76.95
Abstract

DNA computing is a highly interdisciplinary field which combines molecular operations with theoretical algorithm design. A number of algorithms have been demonstrated in DNA computing, but to date network flow problems have not been studied. We aim to provide an approach to calculate the value of the maximum flow in networks by encoding the mathematical problem in DNA molecules and by using molecular biology techniques to manipulate the DNA. We present results which demonstrate that the algorithm works for an example network problem.

Published
2023
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7. Preface

Author

Kalsheker, Noor, primary and Stockley, Robert, additional

Published
2017
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8. List of Contributors

Author

Alam, Samuel, primary, Gooptu, Bibek, additional, Hill, Marian, additional, Irving, James A., additional, Jagger, Alistair, additional, Janciauskiene, Sabina, additional, Kalsheker, Noor, additional, Lomas, David A., additional, Mahadeva, Ravi, additional, Parr, David, additional, Rashid, S. Tamir, additional, Sandhaus, Robert A., additional, Stockley, Robert, additional, Stolk, Jan, additional, Stoller, James K., additional, Strange, Charlie, additional, Sveger, Tomas, additional, Teckman, Jeffrey H., additional, and Turner, Alice, additional

Published
2017
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11. Exome-wide analysis of rare coding variation identifies novel associations with COPD and airflow limitation in MOCS3, IFIT3 and SERPINA12

Author

Jackson, Victoria E, Ntalla, Ioanna, Sayers, Ian, Morris, Richard, Whincup, Peter, Casas, Juan-Pablo, Amuzu, Antoinette, Choi, Minkyoung, Dale, Caroline, Kumari, Meena, Engmann, Jorgen, Kalsheker, Noor, Chappell, Sally, Guetta-Baranes, Tamar, McKeever, Tricia M, Palmer, Colin N A, Tavendale, Roger, Holloway, John W, Sayer, Avan A, Dennison, Elaine M, Cooper, Cyrus, Bafadhel, Mona, Barker, Bethan, Brightling, Chris, Bolton, Charlotte E, John, Michelle E, Parker, Stuart G, Moffat, Miriam F, Wardlaw, Andrew J, Connolly, Martin J, Porteous, David J, Smith, Blair H, Padmanabhan, Sandosh, Hocking, Lynne, Stirrups, Kathleen E, Deloukas, Panos, Strachan, David P, Hall, Ian P, Tobin, Martin D, and Wain, Louise V

Published
2016
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14. Guidance for laboratories performing molecular pathology for cancer patients

Author

Cree, Ian A, Deans, Zandra, Ligtenberg, Marjolijn J L, Normanno, Nicola, Edsjö, Anders, Rouleau, Etienne, Solé, Francesc, Thunnissen, Erik, Timens, Wim, Schuuring, Ed, Dequeker, Elisabeth, Murray, Samuel, Dietel, Manfred, Groenen, Patricia, Van Krieken, J Han, Barnardo, Martin, Blackhall, Fiona, Boone, Elke, Botti, Gerardo, Butler, Rachel, Carneiro, Fatima, Celik, Ilhan, Ciardiello, Fortunato, Collins, Peter, Cotter, Finbarr, Duecker, Klaus, Finn, Stephen, Hall, Marta, Hodges, Elizabeth, Jawaid, Ansar, Jung, Andreas, Kalsheker, Noor, Kamarainen, Outi, Kerr, Keith, Kreipe, Hans, Martin, Jo, Marchetti, Antonio, Marondel, Ivonne, McCormack, Rose, Miller, Keith, Newland, Adrian, Nowak, Frederiqu, Opdam, Frank, Patterson, Scott, Patton, Simon, Paul, John, Pinto, Carmine, Pokinskyj, Peter, Prentice, Archie, Salto-Tellez, Manuel, Santucci, Marco, Sapino, Anna, Shaw, Emily, Siebers, Bert, Stahel, Rolf, Stanta, Giorgio, Szepessy, Edit, Taron, Miquel, Tejpar, Sabine, Vassiliou, George, Wells, Mike, and Wong, Newton

Published
2014
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15. Genetic predisposition to hypertension is associated with preeclampsia in European and Central Asian women

Author

Steinthorsdottir, Valgerdur, McGinnis, Ralph, Williams, Nicholas O., Stefansdottir, Lilja, Thorleifsson, Gudmar, Shooter, Scott, Sigurdsson, Jon K., Auro, Kirsi M., Berezina, Galina, Borges, MariaCarolina, Bumpstead, Suzannah, Bybjerg-Grauholm, Jonas, Colgiu, Irina, Dolby, Vivien A., Dudbridge, Frank, Engel, Stephanie M., Franklin, Christopher S., Frigge, Michael L., Frisbaek, Yr, Geirsson, Reynir T., Geller, Frank, Gretarsdottir, Solveig, Gudbjartsson, Daniel F., Harmon, Quaker, Hougaard, David Michael, Hegay, Tatyana, Helgadottir, Anna, Hjartardottir, Sigrun, Johannsdottir, Hrefna, Jonsdottir, Ingileif, Juliusdottir, Thorhildur, Kalsheker, Noor, Kasimov, Abdumadjit, Kemp, John P., Kivinen, Katja, Lee, Wai K., Melbye, Mads, Miedzybrodska, Zosia, Moffett, Ashley, Najmutdinova, Dilbar, Nishanova, Firuza, Olafsdottir, Thorunn, Perola, Markus, Broughton Pipkin, Fiona, Poston, Lucilla, Prescott, Gordon, Saevarsdottir, Saedis, Salimbayeva, Damilya, Juliet Scaife, Paula, Skotte, Line, Staines-Urias, Eleonora, Stefansson, Olafur A., Cecilie Vestrheim Thomsen, Liv, Tragante, Vinicius, Trogstad, Lill, Simpson, Nigel A.B., FINNPEC Consortium, GOPEC Consortium, Aripova, Tamara, Casas, Juan P., Dominiczak, Anna F., Walker, James J., Thorsteinsdottir, Unnur, Iversen, Ann-Charlotte, Feenstra, Bjarke, Lawlor, Deborah A., Boyd, Heather Allison, Magnus, Per, Laivuori, Hannele, Zakhidova, Nodira, Svyatova, Gulnara, Stefansson, Kari, and Morgan, Linda

Subjects
General Physics and Astronomy, General Chemistry, General Biochemistry, Genetics and Molecular Biology
Published
2020

17. Rare coding variants in the phospholipase D3 gene confer risk for Alzheimer’s disease

Author

Cruchaga, Carlos, Karch, Celeste M., Jin, Sheng Chih, Benitez, Bruno A., Cai, Yefei, Guerreiro, Rita, Harari, Oscar, Norton, Joanne, Budde, John, Bertelsen, Sarah, Jeng, Amanda T., Cooper, Breanna, Skorupa, Tara, Carrell, David, Levitch, Denise, Hsu, Simon, Choi, Jiyoon, Ryten, Mina, Trabzuni, Daniah, Weale, Michael E., Ramasamy, Adaikalavan, Smith, Colin, Sassi, Celeste, Bras, Jose, Gibbs, Raphael J., Hernandez, Dena G., Lupton, Michelle K., Powell, John, Forabosco, Paola, Ridge, Perry G., Corcoran, Christopher D., Tschanz, JoAnn T., Norton, Maria C., Munger, Ronald G., Schmutz, Cameron, Leary, Maegan, Demirci, Yesim F., Bamne, Mikhil N., Wang, Xingbin, Lopez, Oscar L., Ganguli, Mary, Medway, Christopher, Turton, James, Lord, Jenny, Braae, Anne, Barber, Imelda, Passmore, Peter, Craig, David, Johnston, Janet, McGuinness, Bernadette, Todd, Stephen, Heun, Reinhard, Kölsch, Heike, Kehoe, Patrick G., Hooper, Nigel M., Vardy, Emma R.L.C., Mann, David M., Pickering-Brown, Stuart, Brown, Kristelle, Kalsheker, Noor, Lowe, James, Morgan, Kevin, Smith, David A., Wilcock, Gordon, Warden, Donald, Holmes, Clive, Pastor, Pau, Lorenzo-Betancor, Oswaldo, Brkanac, Zoran, Scott, Erick, Topol, Eric, Rogaeva, Ekaterina, Singleton, Andrew B., Hardy, John, Kamboh, Ilyas M., St George-Hyslop, Peter, Cairns, Nigel, Morris, John C., Kauwe, John S. K., and Goate, Alison M.

Published
2014
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25. Genetic landscape of chronic obstructive pulmonary disease identifies heterogeneous cell-type and phenotype associations

Author

Sakornsakolpat, Phuwanat, Prokopenko, Dmitry, Lamontagne, Maxime, Reeve, Nicola F., Guyatt, Anna L., Jackson, Victoria E., Shrine, Nick, Qiao, Dandi, Bartz, Traci M., Kim, Deog Kyeom, Lee, Mi Kyeong, Latourelle, Jeanne C., Li, Xingnan, Morrow, Jarrett D., Obeidat, Ma’en, Wyss, Annah B., Bakke, Per, Barr, R. Graham, Beaty, Terri H., Belinsky, Steven A., Brusselle, Guy G., Crapo, James D., de Jong, Kim, DeMeo, Dawn L., Fingerlin, Tasha E., Gharib, Sina A., Gulsvik, Amund, Hall, Ian P., Hokanson, John E., Kim, Woo Jin, Lomas, David A., London, Stephanie J., Meyers, Deborah A., O’Connor, George T., Rennard, Stephen I., Schwartz, David A., Sliwinski, Pawel, Sparrow, David, Strachan, David P., Tal-Singer, Ruth, Tesfaigzi, Yohannes, Vestbo, Jørgen, Vonk, Judith M., Yim, Jae-Joon, Zhou, Xiaobo, Bossé, Yohan, Manichaikul, Ani, Lahousse, Lies, Silverman, Edwin K., Boezen, H. Marike, Wain, Louise V., Tobin, Martin D., Hobbs, Brian D., Cho, Michael H., Batini, Chiara, Zhao, Jing Hua, Wielscher, Matthias, Weiss, Stefan, Kentistou, Katherine A., Cook, James P., Hui, Jennie, Karrasch, Stefan, Imboden, Medea, Harris, Sarah E., Marten, Jonathan, Enroth, Stefan, Kerr, Shona M., Surakka, Ida, Vitart, Veronique, Lehtimäki, Terho, Ewert, Ralf, Gieger, Christian, Homuth, Georg, Joshi, Peter K., Langenberg, Claudia, Lind, Lars, Luan, Jian’an, Mahajan, Anubha, Murray, Alison, Porteous, David J., Rawal, Rajesh, Smith, Blair H., Timmers, Paul R. H. J., Raitakari, Olli T., Kähönen, Mika, Polasek, Ozren, Gyllensten, Ulf, Rudan, Igor, Deary, Ian J., Probst-Hensch, Nicole M., Schulz, Holger, James, Alan L., Wilson, James F., Stubbe, Beate, Zeggini, Eleftheria, Jarvelin, Marjo-Riitta, Wareham, Nick, Hayward, Caroline, Morris, Andrew P., Agusti, Alvar, Anderson, Wayne, Bakerly, Nawar, Bals, Robert, Barnes, Kathleen C., Bleecker, Eugene R., Bowler, Russell, Brightling, Christopher, de Bruijne, Marleen, Castaldi, Peter J., Celli, Bartolome, Coxson, Harvey O., Crystal, Ron, de Jong, Pim, Dirksen, Asger, Dy, Jennifer, Foreman, Marilyn, Garcia-Aymerich, Judith, Gevenois, Pierre, Ghosh, Soumitra, Gietema, Hester, Hansel, Nadia, Hersh, Craig P., Hoffman, Eric, Kalsheker, Noor, Kauczor, Hans-Ulrich, Laitinen, Tarja, Lambrechts, Diether, Lee, Sang-Do, Litonjua, Augusto A., Loth, Daan W., Lutz, Sharon M., Lynch, David, MacNee, William, McDonald, Merry-Lynn, Newell, John D., Nordestgaard, Borge G., Oh, Yeon-Mok, Paré, Peter D., Pistolesi, Massimo, Postma, Dirkje S., Puhan, Milo, Regan, Elizabeth, Rich, Stephen S., Seo, Joon Beom, Short, Andrea, Stoel, Berend, Sverzellati, Nicola, ter Riet, Gerben, Van Beek, Edwin J. R., van Ginneken, Bram, Vogelmeier, Claus F., Wanner, Adam, Washko, George, Wauters, Els, Wouters, Emiel F. M., Young, Robert P., Zeigler-Heitbrock, Loems, SpiroMeta Consortium, Understanding Society Scientific Group, International COPD Genetics Consortium, Institute for Molecular Medicine Finland, Groningen Research Institute for Asthma and COPD (GRIAC), Life Course Epidemiology (LCE), Beeldvorming, MUMC+: DA BV Medisch Specialisten Radiologie (9), MUMC+: MA Longziekten (3), RS: NUTRIM - R3 - Respiratory & Age-related Health, Pulmonologie, General practice, APH - Aging & Later Life, APH - Personalized Medicine, ACS - Diabetes & metabolism, Epidemiology, Pulmonary Medicine, Medical Informatics, and Radiology & Nuclear Medicine

Subjects
Male, Lydia Becker Institute, Pulmonary Fibrosis, LD SCORE REGRESSION, Gene Expression, Genome-wide association study, Pulmonary Disease, Chronic Obstructive, 0302 clinical medicine, Pulmonary fibrosis, GWAS, Lung, GENOME-WIDE ASSOCIATION, ACIDIC-MAMMALIAN-CHITINASE, LUNG-FUNCTION, EXTRACELLULAR-MATRIX, PREDOMINANT EMPHYSEMA, CONNECTIVITY MAP, ATOPIC ASTHMA, RISK LOCI, 0303 health sciences, COPD, education.field_of_study, Smoking, 1184 Genetics, developmental biology, physiology, Middle Aged, 3. Good health, Phenotype, medicine.anatomical_structure, Medical genetics, Female, Rare cancers Radboud Institute for Health Sciences [Radboudumc 9], Adult, medicine.medical_specialty, Population, Biology, Polymorphism, Single Nucleotide, Article, 03 medical and health sciences, All institutes and research themes of the Radboud University Medical Center, ResearchInstitutes_Networks_Beacons/lydia_becker_institute_of_immunology_and_inflammation, Genetics, medicine, Genetic predisposition, Humans, Genetic Predisposition to Disease, education, Aged, 030304 developmental biology, Asthma, medicine.disease, respiratory tract diseases, Genetic Loci, Case-Control Studies, Immunology, 3111 Biomedicine, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract

Chronic obstructive pulmonary disease (COPD) is the leading cause of respiratory mortality worldwide. Genetic risk loci provide novel insights into disease pathogenesis. We performed a genome-wide association study in 35,735 cases and 222,076 controls from the UK Biobank and additional studies from the International COPD Genetics Consortium. We identified 82 loci with P-value < 5 × 10−8; 47 were previously described in association with either COPD or population-based lung function. Of the remaining 35 novel loci, 13 were associated with lung function in 79,055 individuals from the SpiroMeta consortium. Using gene expression and regulation data, we identified enrichment for loci in lung tissue, smooth muscle and several lung cell types. We found 14 COPD loci shared with either asthma or pulmonary fibrosis. COPD genetic risk loci clustered into groups of quantitative imaging features and comorbidity associations. Our analyses provide further support to the genetic susceptibility and heterogeneity of COPD., Editorial summary Genome-wide analysis of chronic obstructive pulmonary disease identifies 82 loci, 35 of which are new. Integration of gene expression and genomic annotation data shows enrichment of signals in lung tissue, smooth muscle and several lung cell types.

Published
2019
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37. The role of IREB2 and transforming growth factor beta-1 genetic variants in COPD: a replication case-control study

Author

Stolk Jan, MacNee William, Keatings Vera, Donnelly Seamas C, Millar Ann B, Morgan Kevin, Rabinovich Roberto, Roca Josep, Guetta-Baranes Tamar, Alsaegh Aiman, Lotya Juzer, Daly Leslie, Chappell Sally L, Hiemstra Pieter S, Miniati Massimo, Monti Simonetta, O'Connor Clare M, and Kalsheker Noor

Subjects
Internal medicine, RC31-1245, Genetics, QH426-470
Abstract

Abstract Background Genetic factors are known to contribute to COPD susceptibility and these factors are not fully understood. Conflicting results have been reported for many genetic studies of candidate genes based on their role in the disease. Genome-wide association studies in combination with expression profiling have identified a number of new candidates including IREB2. A meta-analysis has implicated transforming growth factor beta-1 (TGFbeta1) as a contributor to disease susceptibility. Methods We have examined previously reported associations in both genes in a collection of 1017 white COPD patients and 912 non-diseased smoking controls. Genotype information was obtained for seven SNPs in the IREB2 gene, and for four SNPs in the TGFbeta1 gene. Allele and genotype frequencies were compared between COPD cases and controls, and odds ratios were calculated. The analysis was adjusted for age, sex, smoking and centre, including interactions of age, sex and smoking with centre. Results Our data replicate the association of IREB2 SNPs in association with COPD for SNP rs2568494, rs2656069 and rs12593229 with respective adjusted p-values of 0.0018, 0.0039 and 0.0053. No significant associations were identified for TGFbeta1. Conclusions These studies have therefore confirmed that the IREB2 locus is a contributor to COPD susceptibility and suggests a new pathway in COPD pathogenesis invoking iron homeostasis.

Published
2011
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38. Association of MMP - 12 polymorphisms with severe and very severe COPD: A case control study of MMPs - 1, 9 and 12 in a European population

Author

Keatings Vera, Donnelly Seamas C, Millar Ann B, Rabinovich Roberto, Roca Josep, Guetta-Baranes Tamar, Morgan Kevin, Daly Leslie, Lotya Juzer, Johnson Simon R, Chappell Sally, Haq Imran, MacNee William, Stolk Jan, Hiemstra Pieter S, Miniati Massimo, Monti Simonetta, O'Connor Clare M, and Kalsheker Noor

Subjects
Internal medicine, RC31-1245, Genetics, QH426-470
Abstract

Abstract Background Genetic factors play a role in chronic obstructive pulmonary disease (COPD) but are poorly understood. A number of candidate genes have been proposed on the basis of the pathogenesis of COPD. These include the matrix metalloproteinase (MMP) genes which play a role in tissue remodelling and fit in with the protease - antiprotease imbalance theory for the cause of COPD. Previous genetic studies of MMPs in COPD have had inadequate coverage of the genes, and have reported conflicting associations of both single nucleotide polymorphisms (SNPs) and SNP haplotypes, plausibly due to under-powered studies. Methods To address these issues we genotyped 26 SNPs, providing comprehensive coverage of reported SNP variation, in MMPs- 1, 9 and 12 from 977 COPD patients and 876 non-diseased smokers of European descent and evaluated their association with disease singly and in haplotype combinations. We used logistic regression to adjust for age, gender, centre and smoking history. Results Haplotypes of two SNPs in MMP-12 (rs652438 and rs2276109), showed an association with severe/very severe disease, corresponding to GOLD Stages III and IV. Conclusions Those with the common A-A haplotype for these two SNPs were at greater risk of developing severe/very severe disease (p = 0.0039) while possession of the minor G variants at either SNP locus had a protective effect (adjusted odds ratio of 0.76; 95% CI 0.61 - 0.94). The A-A haplotype was also associated with significantly lower predicted FEV1 (42.62% versus 44.79%; p = 0.0129). This implicates haplotypes of MMP-12 as modifiers of disease severity.

Published
2010
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44. Variants in the fetal genome near FLT1 are associated with risk of preeclampsia

Author

McGinnis, Ralph, Steinthorsdottir, Valgerdur, Williams, Nicholas O, Thorleifsson, Gudmar, Shooter, Scott, Hjartardottir, Sigrun, Bumpstead, Suzannah, Stefansdottir, Lilja, Hildyard, Lucy, Sigurdsson, Jon K, Kemp, John P, Silva, Gabriela B, Thomsen, Liv Cecilie V, Jääskeläinen, Tiina, Kajantie, Eero, Chappell, Sally, Kalsheker, Noor, Moffett, Ashley, Hiby, Susan, Lee, Wai Kwong, Padmanabhan, Sandosh, Simpson, Nigel AB, Dolby, Vivien A, Staines-Urias, Eleonora, Engel, Stephanie M, Haugan, Anita, Trogstad, Lill, Svyatova, Gulnara, Zakhidova, Nodira, Najmutdinova, Dilbar, FINNPEC Consortium, GOPEC Consortium, Dominiczak, Anna F, Gjessing, Håkon K, Casas, Juan P, Dudbridge, Frank, Walker, James J, Pipkin, Fiona Broughton, Thorsteinsdottir, Unnur, Geirsson, Reynir T, Lawlor, Debbie A, Iversen, Ann-Charlotte, Magnus, Per, Laivuori, Hannele, Stefansson, Kari, and Morgan, Linda

Subjects
embryonic structures, female genital diseases and pregnancy complications, reproductive and urinary physiology
Abstract

Preeclampsia, which affects approximately 5% of pregnancies, is a leading cause of maternal and perinatal death. The causes of preeclampsia remain unclear, but there is evidence for inherited susceptibility. Genome-wide association studies (GWAS) have not identified maternal sequence variants of genome-wide significance that replicate in independent data sets. We report the first GWAS of offspring from preeclamptic pregnancies and discovery of the first genome-wide significant susceptibility locus (rs4769613; P = 5.4 × 10-11) in 4,380 cases and 310,238 controls. This locus is near the FLT1 gene encoding Fms-like tyrosine kinase 1, providing biological support, as a placental isoform of this protein (sFlt-1) is implicated in the pathology of preeclampsia. The association was strongest in offspring from pregnancies in which preeclampsia developed during late gestation and offspring birth weights exceeded the tenth centile. An additional nearby variant, rs12050029, associated with preeclampsia independently of rs4769613. The newly discovered locus may enhance understanding of the pathophysiology of preeclampsia and its subtypes.

Published
2017

47. Copy number variation of the beta-defensin genes in Europeans: no supporting evidence for association with lung function, chronic obstructive pulmonary disease or asthma

Author

Ahuja, Sunil K., Wain, Louise V., Odenthal-Hesse, Linda, Abujaber, Razan, Sayers, Ian, Beardsmore, Caroline, Gaillard, Erol A., Chappell, Sally, Dogaru, Cristian M., McKeever, Tricia M., Guetta-Baranes, Tamar, Kalsheker, Noor, Kuehni, Claudia E., Hall, Ian P., Tobin, Martin D., and Hollox, Edward J.

Subjects
Male, beta-Defensins, Pulmonology, Chronic Obstructive Pulmonary Diseases, Epidemiology, Genome-wide association study, Pulmonary Disease, Chronic Obstructive, Missing heritability problem, Gene Duplication, Copy-number variation, Child, Aged, 80 and over, Genetics, education.field_of_study, COPD, Multidisciplinary, Middle Aged, 3. Good health, Genetic Epidemiology, Medicine, Female, Research Article, Adult, Adolescent, DNA Copy Number Variations, Science, Population, 610 Medicine & health, Single-nucleotide polymorphism, White People, Molecular Genetics, 360 Social problems & social services, medicine, Humans, Genetic Predisposition to Disease, education, Biology, Genetic Association Studies, Aged, Asthma, Population Biology, business.industry, Case-control study, Human Genetics, medicine.disease, respiratory tract diseases, Case-Control Studies, Genetics of Disease, Immunology, Genetic Polymorphism, business, Population Genetics
Abstract

Lung function measures are heritable, predict mortality and are relevant in diagnosis of chronic obstructive pulmonary disease (COPD). COPD and asthma are diseases of the airways with major public health impacts and each have a heritable component. Genome-wide association studies of SNPs have revealed novel genetic associations with both diseases but only account for a small proportion of the heritability. Complex copy number variation may account for some of the missing heritability. A well-characterised genomic region of complex copy number variation contains beta-defensin genes (DEFB103, DEFB104 and DEFB4), which have a role in the innate immune response. Previous studies have implicated these and related genes as being associated with asthma or COPD. We hypothesised that copy number variation of these genes may play a role in lung function in the general population and in COPD and asthma risk. We undertook copy number typing of this locus in 1149 adult and 689 children using a paralogue ratio test and investigated association with COPD, asthma and lung function. Replication of findings was assessed in a larger independent sample of COPD cases and smoking controls. We found evidence for an association of beta-defensin copy number with COPD in the adult cohort (OR = 1.4, 95%CI:1.02–1.92, P = 0.039) but this finding, and findings from a previous study, were not replicated in a larger follow-up sample(OR = 0.89, 95%CI:0.72–1.07, P = 0.217). No robust evidence of association with asthma in children was observed. We found no evidence for association between beta-defensin copy number and lung function in the general populations. Our findings suggest that previous reports of association of beta-defensin copy number with COPD should be viewed with caution. Suboptimal measurement of copy number can lead to spurious associations. Further beta-defensin copy number measurement in larger sample sizes of COPD cases and children with asthma are needed.

Published
2014
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49. Next generation sequencing of CLU, PICALM and CR1: pitfalls and potential solutions

Author

Lord, Jenny, Turton, James, Medway, Christopher, Shi, Hui, Brown, Kristelle, Lowe, James, Mann, David, Pickering-Brown, Stuart, Kalsheker, Noor, Passmore, Peter, Morgan, Kevin, and Alzheimers Research UK Consortium

Abstract

CLU, PICALM and CR1 were identified as genetic risk factors for late onset Alzheimer’s disease (AD) in two large genome wide association studies (GWAS) published in 2009, but the variants that convey this alteration in disease risk, and how the genes relate to AD pathology is yet to be discovered. A next generation sequencing (NGS) project was conducted targeting CLU, CR1 and PICALM, in 96 AD samples (8 pools of 12), in an attempt to discover rare variants within these AD associated genes. Inclusion of repetitive regions in the design of the SureSelect capture lead to significant issues in alignment of the data, leading to poor specificity and a lower than expected depth of coverage. A strong positive correlation (0.964, p

Published
2012

50. The Future Role of Biomarkers in Alzheimer’s Disease Diagnostics

Author

Morgan, Kevin, Carrasquillo, Minerva M., Richens, Joanna L., Vafadar-Isfahani, Bharak, Vere, Kelly Ann, Ball, Graham, Kalsheker, Noor, Rees, Robert, Bajaj, Nin, O'Shea, Paul, Morgan, Kevin, Carrasquillo, Minerva M., Richens, Joanna L., Vafadar-Isfahani, Bharak, Vere, Kelly Ann, Ball, Graham, Kalsheker, Noor, Rees, Robert, Bajaj, Nin, and O'Shea, Paul

Abstract

Diagnosis of Alzheimer's disease can be confirmed presently only upon post-mortem examination of amyloid plaques and neurofibrillary tangles in brain tissue. Developments in diagnostic imaging tools including MRI, PET and SPECT scans are enabling greater insight into these pathologies but these techniques are insufficient for disease stratification or early diagnosis and ideally would be employed alongside diagnostics tests for biochemical biomarkers of disease. Attempts to identify biomarkers for Alzheimer's disease have centred on the beta amyloid and tau pathologies characteristic of disease, but advances in genomic and proteomic technologies are facilitating a more complete approach to biomarker discovery. Here we discuss the impact such technologies could potentially achieve in Alzheimer's disease diagnostics.

Published
2013

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