249 research outputs found

    Human genome meeting 2016 : Houston, TX, USA. 28 February - 2 March 2016

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    : O1 The metabolomics approach to autism: identification of biomarkers for early detection of autism spectrum disorder A. K. Srivastava, Y. Wang, R. Huang, C. Skinner, T. Thompson, L. Pollard, T. Wood, F. Luo, R. Stevenson O2 Phenome-wide association study for smoking- and drinking-associated genes in 26,394 American women with African, Asian, European, and Hispanic descents R. Polimanti, J. Gelernter O3 Effects of prenatal environment, genotype and DNA methylation on birth weight and subsequent postnatal outcomes: findings from GUSTO, an Asian birth cohort X. Lin, I. Y. Lim, Y. Wu, A. L. Teh, L. Chen, I. M. Aris, S. E. Soh, M. T. Tint, J. L. MacIsaac, F. Yap, K. Kwek, S. M. Saw, M. S. Kobor, M. J. Meaney, K. M. Godfrey, Y. S. Chong, J. D. Holbrook, Y. S. Lee, P. D. Gluckman, N. Karnani, GUSTO study group O4 High-throughput identification of specific qt interval modulating enhancers at the SCN5A locus A. Kapoor, D. Lee, A. Chakravarti O5 Identification of extracellular matrix components inducing cancer cell migration in the supernatant of cultivated mesenchymal stem cells C. Maercker, F. Graf, M. Boutros O6 Single cell allele specific expression (ASE) IN T21 and common trisomies: a novel approach to understand DOWN syndrome and other aneuploidies G. Stamoulis, F. Santoni, P. Makrythanasis, A. Letourneau, M. Guipponi, N. Panousis, M. Garieri, P. Ribaux, E. Falconnet, C. Borel, S. E. Antonarakis O7 Role of microRNA in LCL to IPSC reprogramming S. Kumar, J. Curran, J. Blangero O8 Multiple enhancer variants disrupt gene regulatory network in Hirschsprung disease S. Chatterjee, A. Kapoor, J. Akiyama, D. Auer, C. Berrios, L. Pennacchio, A. Chakravarti O9 Metabolomic profiling for the diagnosis of neurometabolic disorders T. R. Donti, G. Cappuccio, M. Miller, P. Atwal, A. Kennedy, A. Cardon, C. Bacino, L. Emrick, J. Hertecant, F. Baumer, B. Porter, M. Bainbridge, P. Bonnen, B. Graham, R. Sutton, Q. Sun, S. Elsea O10 A novel causal methylation network approach to Alzheimer’s disease Z. Hu, P. Wang, Y. Zhu, J. Zhao, M. Xiong, David A Bennett O11 A microRNA signature identifies subtypes of triple-negative breast cancer and reveals MIR-342-3P as regulator of a lactate metabolic pathway A. Hidalgo-Miranda, S. Romero-Cordoba, S. Rodriguez-Cuevas, R. Rebollar-Vega, E. Tagliabue, M. Iorio, E. D’Ippolito, S. Baroni O12 Transcriptome analysis identifies genes, enhancer RNAs and repetitive elements that are recurrently deregulated across multiple cancer types B. Kaczkowski, Y. Tanaka, H. Kawaji, A. Sandelin, R. Andersson, M. Itoh, T. Lassmann, the FANTOM5 consortium, Y. Hayashizaki, P. Carninci, A. R. R. Forrest O13 Elevated mutation and widespread loss of constraint at regulatory and architectural binding sites across 11 tumour types C. A. Semple O14 Exome sequencing provides evidence of pathogenicity for genes implicated in colorectal cancer E. A. Rosenthal, B. Shirts, L. Amendola, C. Gallego, M. Horike-Pyne, A. Burt, P. Robertson, P. Beyers, C. Nefcy, D. Veenstra, F. Hisama, R. Bennett, M. Dorschner, D. Nickerson, J. Smith, K. Patterson, D. Crosslin, R. Nassir, N. Zubair, T. Harrison, U. Peters, G. Jarvik, NHLBI GO Exome Sequencing Project O15 The tandem duplicator phenotype as a distinct genomic configuration in cancer F. Menghi, K. Inaki, X. Woo, P. Kumar, K. Grzeda, A. Malhotra, H. Kim, D. Ucar, P. Shreckengast, K. Karuturi, J. Keck, J. Chuang, E. T. Liu O16 Modeling genetic interactions associated with molecular subtypes of breast cancer B. Ji, A. Tyler, G. Ananda, G. Carter O17 Recurrent somatic mutation in the MYC associated factor X in brain tumors H. Nikbakht, M. Montagne, M. Zeinieh, A. Harutyunyan, M. Mcconechy, N. Jabado, P. Lavigne, J. Majewski O18 Predictive biomarkers to metastatic pancreatic cancer treatment J. B. Goldstein, M. Overman, G. Varadhachary, R. Shroff, R. Wolff, M. Javle, A. Futreal, D. Fogelman O19 DDIT4 gene expression as a prognostic marker in several malignant tumors L. Bravo, W. Fajardo, H. Gomez, C. Castaneda, C. Rolfo, J. A. Pinto O20 Spatial organization of the genome and genomic alterations in human cancers K. C. Akdemir, L. Chin, A. Futreal, ICGC PCAWG Structural Alterations Group O21 Landscape of targeted therapies in solid tumors S. Patterson, C. Statz, S. Mockus O22 Genomic analysis reveals novel drivers and progression pathways in skin basal cell carcinoma S. N. Nikolaev, X. I. Bonilla, L. Parmentier, B. King, F. Bezrukov, G. Kaya, V. Zoete, V. Seplyarskiy, H. Sharpe, T. McKee, A. Letourneau, P. Ribaux, K. Popadin, N. Basset-Seguin, R. Ben Chaabene, F. Santoni, M. Andrianova, M. Guipponi, M. Garieri, C. Verdan, K. Grosdemange, O. Sumara, M. Eilers, I. Aifantis, O. Michielin, F. de Sauvage, S. Antonarakis O23 Identification of differential biomarkers of hepatocellular carcinoma and cholangiocarcinoma via transcriptome microarray meta-analysis S. Likhitrattanapisal O24 Clinical validity and actionability of multigene tests for hereditary cancers in a large multi-center study S. Lincoln, A. Kurian, A. Desmond, S. Yang, Y. Kobayashi, J. Ford, L. Ellisen O25 Correlation with tumor ploidy status is essential for correct determination of genome-wide copy number changes by SNP array T. L. Peters, K. R. Alvarez, E. F. Hollingsworth, D. H. Lopez-Terrada O26 Nanochannel based next-generation mapping for interrogation of clinically relevant structural variation A. Hastie, Z. Dzakula, A. W. Pang, E. T. Lam, T. Anantharaman, M. Saghbini, H. Cao, BioNano Genomics O27 Mutation spectrum in a pulmonary arterial hypertension (PAH) cohort and identification of associated truncating mutations in TBX4 C. Gonzaga-Jauregui, L. Ma, A. King, E. Berman Rosenzweig, U. Krishnan, J. G. Reid, J. D. Overton, F. Dewey, W. K. Chung O28 NORTH CAROLINA macular dystrophy (MCDR1): mutations found affecting PRDM13 K. Small, A. DeLuca, F. Cremers, R. A. Lewis, V. Puech, B. Bakall, R. Silva-Garcia, K. Rohrschneider, M. Leys, F. S. Shaya, E. Stone O29 PhenoDB and genematcher, solving unsolved whole exome sequencing data N. L. Sobreira, F. Schiettecatte, H. Ling, E. Pugh, D. Witmer, K. Hetrick, P. Zhang, K. Doheny, D. Valle, A. Hamosh O30 Baylor-Johns Hopkins Center for Mendelian genomics: a four year review S. N. Jhangiani, Z. Coban Akdemir, M. N. Bainbridge, W. Charng, W. Wiszniewski, T. Gambin, E. Karaca, Y. Bayram, M. K. Eldomery, J. Posey, H. Doddapaneni, J. Hu, V. R. Sutton, D. M. Muzny, E. A. Boerwinkle, D. Valle, J. R. Lupski, R. A. Gibbs O31 Using read overlap assembly to accurately identify structural genetic differences in an ashkenazi jewish trio S. Shekar, W. Salerno, A. English, A. Mangubat, J. Bruestle O32 Legal interoperability: a sine qua non for international data sharing A. Thorogood, B. M. Knoppers, Global Alliance for Genomics and Health - Regulatory and Ethics Working Group O33 High throughput screening platform of competent sineups: that can enhance translation activities of therapeutic target H. Takahashi, K. R. Nitta, A. Kozhuharova, A. M. Suzuki, H. Sharma, D. Cotella, C. Santoro, S. Zucchelli, S. Gustincich, P. Carninci O34 The undiagnosed diseases network international (UDNI): clinical and laboratory research to meet patient needs J. J. Mulvihill, G. Baynam, W. Gahl, S. C. Groft, K. Kosaki, P. Lasko, B. Melegh, D. Taruscio O36 Performance of computational algorithms in pathogenicity predictions for activating variants in oncogenes versus loss of function mutations in tumor suppressor genes R. Ghosh, S. Plon O37 Identification and electronic health record incorporation of clinically actionable pharmacogenomic variants using prospective targeted sequencing S. Scherer, X. Qin, R. Sanghvi, K. Walker, T. Chiang, D. Muzny, L. Wang, J. Black, E. Boerwinkle, R. Weinshilboum, R. Gibbs O38 Melanoma reprogramming state correlates with response to CTLA-4 blockade in metastatic melanoma T. Karpinets, T. Calderone, K. Wani, X. Yu, C. Creasy, C. Haymaker, M. Forget, V. Nanda, J. Roszik, J. Wargo, L. Haydu, X. Song, A. Lazar, J. Gershenwald, M. Davies, C. Bernatchez, J. Zhang, A. Futreal, S. Woodman O39 Data-driven refinement of complex disease classification from integration of heterogeneous functional genomics data in GeneWeaver E. J. Chesler, T. Reynolds, J. A. Bubier, C. Phillips, M. A. Langston, E. J. Baker O40 A general statistic framework for genome-based disease risk prediction M. Xiong, L. Ma, N. Lin, C. Amos O41 Integrative large-scale causal network analysis of imaging and genomic data and its application in schizophrenia studies N. Lin, P. Wang, Y. Zhu, J. Zhao, V. Calhoun, M. Xiong O42 Big data and NGS data analysis: the cloud to the rescue O. Dobretsberger, M. Egger, F. Leimgruber O43 Cpipe: a convergent clinical exome pipeline specialised for targeted sequencing S. Sadedin, A. Oshlack, Melbourne Genomics Health Alliance O44 A Bayesian classification of biomedical images using feature extraction from deep neural networks implemented on lung cancer data V. A. A. Antonio, N. Ono, Clark Kendrick C. Go O45 MAV-SEQ: an interactive platform for the Management, Analysis, and Visualization of sequence data Z. Ahmed, M. Bolisetty, S. Zeeshan, E. Anguiano, D. Ucar O47 Allele specific enhancer in EPAS1 intronic regions may contribute to high altitude adaptation of Tibetans C. Zeng, J. Shao O48 Nanochannel based next-generation mapping for structural variation detection and comparison in trios and populations H. Cao, A. Hastie, A. W. Pang, E. T. Lam, T. Liang, K. Pham, M. Saghbini, Z. Dzakula O49 Archaic introgression in indigenous populations of Malaysia revealed by whole genome sequencing Y. Chee-Wei, L. Dongsheng, W. Lai-Ping, D. Lian, R. O. Twee Hee, Y. Yunus, F. Aghakhanian, S. S. Mokhtar, C. V. Lok-Yung, J. Bhak, M. Phipps, X. Shuhua, T. Yik-Ying, V. Kumar, H. Boon-Peng O50 Breast and ovarian cancer prevention: is it time for population-based mutation screening of high risk genes? I. Campbell, M.-A. Young, P. James, Lifepool O53 Comprehensive coverage from low DNA input using novel NGS library preparation methods for WGS and WGBS C. Schumacher, S. Sandhu, T. Harkins, V. Makarov O54 Methods for large scale construction of robust PCR-free libraries for sequencing on Illumina HiSeqX platform H. DoddapaneniR. Glenn, Z. Momin, B. Dilrukshi, H. Chao, Q. Meng, B. Gudenkauf, R. Kshitij, J. Jayaseelan, C. Nessner, S. Lee, K. Blankenberg, L. Lewis, J. Hu, Y. Han, H. Dinh, S. Jireh, K. Walker, E. Boerwinkle, D. Muzny, R. Gibbs O55 Rapid capture methods for clinical sequencing J. Hu, K. Walker, C. Buhay, X. Liu, Q. Wang, R. Sanghvi, H. Doddapaneni, Y. Ding, N. Veeraraghavan, Y. Yang, E. Boerwinkle, A. L. Beaudet, C. M. Eng, D. M. Muzny, R. A. Gibbs O56 A diploid personal human genome model for better genomes from diverse sequence data K. C. C. Worley, Y. Liu, D. S. T. Hughes, S. C. Murali, R. A. Harris, A. C. English, X. Qin, O. A. Hampton, P. Larsen, C. Beck, Y. Han, M. Wang, H. Doddapaneni, C. L. Kovar, W. J. Salerno, A. Yoder, S. Richards, J. Rogers, J. R. Lupski, D. M. Muzny, R. A. Gibbs O57 Development of PacBio long range capture for detection of pathogenic structural variants Q. Meng, M. Bainbridge, M. Wang, H. Doddapaneni, Y. Han, D. Muzny, R. Gibbs O58 Rhesus macaques exhibit more non-synonymous variation but greater impact of purifying selection than humans R. A. Harris, M. Raveenedran, C. Xue, M. Dahdouli, L. Cox, G. Fan, B. Ferguson, J. Hovarth, Z. Johnson, S. Kanthaswamy, M. Kubisch, M. Platt, D. Smith, E. Vallender, R. Wiseman, X. Liu, J. Below, D. Muzny, R. Gibbs, F. Yu, J. Rogers O59 Assessing RNA structure disruption induced by single-nucleotide variation J. Lin, Y. Zhang, Z. Ouyang P1 A meta-analysis of genome-wide association studies of mitochondrial dna copy number A. Moore, Z. Wang, J. Hofmann, M. Purdue, R. Stolzenberg-Solomon, S. Weinstein, D. Albanes, C.-S. Liu, W.-L. Cheng, T.-T. Lin, Q. Lan, N. Rothman, S. Berndt P2 Missense polymorphic genetic combinations underlying down syndrome susceptibility E. S. Chen P4 The evaluation of alteration of ELAM-1 expression in the endometriosis patients H. Bahrami, A. Khoshzaban, S. Heidari Keshal P5 Obesity and the incidence of apolipoprotein E polymorphisms in an assorted population from Saudi Arabia population K. K. R. Alharbi P6 Genome-associated personalized antithrombotical therapy for patients with high risk of thrombosis and bleeding M. Zhalbinova, A. Akilzhanova, S. Rakhimova, M. Bekbosynova, S. Myrzakhmetova P7 Frequency of Xmn1 polymorphism among sickle cell carrier cases in UAE population M. Matar P8 Differentiating inflammatory bowel diseases by using genomic data: dimension of the problem and network organization N. Mili, R. Molinari, Y. Ma, S. Guerrier P9 Vulnerability of genetic variants to the risk of autism among Saudi children N. Elhawary, M. Tayeb, N. Bogari, N. Qotb P10 Chromatin profiles from ex vivo purified dopaminergic neurons establish a promising model to support studies of neurological function and dysfunction S. A. McClymont, P. W. Hook, L. A. Goff, A. McCallion P11 Utilization of a sensitized chemical mutagenesis screen to identify genetic modifiers of retinal dysplasia in homozygous Nr2e3rd7 mice Y. Kong, J. R. Charette, W. L. Hicks, J. K. Naggert, L. Zhao, P. M. Nishina P12 Ion torrent next generation sequencing of recessive polycystic kidney disease in Saudi patients B. M. Edrees, M. Athar, F. A. Al-Allaf, M. M. Taher, W. Khan, A. Bouazzaoui, N. A. Harbi, R. Safar, H. Al-Edressi, A. Anazi, N. Altayeb, M. A. Ahmed, K. Alansary, Z. Abduljaleel P13 Digital expression profiling of Purkinje neurons and dendrites in different subcellular compartments A. Kratz, P. Beguin, S. Poulain, M. Kaneko, C. Takahiko, A. Matsunaga, S. Kato, A. M. Suzuki, N. Bertin, T. Lassmann, R. Vigot, P. Carninci, C. Plessy, T. Launey P14 The evolution of imperfection and imperfection of evolution: the functional and functionless fractions of the human genome D. Graur P16 Species-independent identification of known and novel recurrent genomic entities in multiple cancer patients J. Friis-Nielsen, J. M. Izarzugaza, S. Brunak P18 Discovery of active gene modules which are densely conserved across multiple cancer types reveal their prognostic power and mutually exclusive mutation patterns B. S. Soibam P19 Whole exome sequencing of dysplastic leukoplakia tissue indicates sequential accumulation of somatic mutations from oral precancer to cancer D. Das, N. Biswas, S. Das, S. Sarkar, A. Maitra, C. Panda, P. Majumder P21 Epigenetic mechanisms of carcinogensis by hereditary breast cancer genes J. J. Gruber, N. Jaeger, M. Snyder P22 RNA direct: a novel RNA enrichment strategy applied to transcripts associated with solid tumors K. Patel, S. Bowman, T. Davis, D. Kraushaar, A. Emerman, S. Russello, N. Henig, C. Hendrickson P23 RNA sequencing identifies gene mutations for neuroblastoma K. Zhang P24 Participation of SFRP1 in the modulation of TMPRSS2-ERG fusion gene in prostate cancer cell lines M. Rodriguez-Dorantes, C. D. Cruz-Hernandez, C. D. P. Garcia-Tobilla, S. Solorzano-Rosales P25 Targeted Methylation Sequencing of Prostate Cancer N. Jäger, J. Chen, R. Haile, M. Hitchins, J. D. Brooks, M. Snyder P26 Mutant TPMT alleles in children with acute lymphoblastic leukemia from México City and Yucatán, Mexico S. Jiménez-Morales, M. Ramírez, J. Nuñez, V. Bekker, Y. Leal, E. Jiménez, A. Medina, A. Hidalgo, J. Mejía P28 Genetic modifiers of Alström syndrome J. Naggert, G. B. Collin, K. DeMauro, R. Hanusek, P. M. Nishina P31 Association of genomic variants with the occurrence of angiotensin-converting-enzyme inhibitor (ACEI)-induced coughing among Filipinos E. M. Cutiongco De La Paz, R. Sy, J. Nevado, P. Reganit, L. Santos, J. D. Magno, F. E. Punzalan , D. Ona , E. Llanes, R. L. Santos-Cortes , R. Tiongco, J. Aherrera, L. Abrahan, P. Pagauitan-Alan; Philippine Cardiogenomics Study Group P32 The use of “humanized” mouse models to validate disease association of a de novo GARS variant and to test a novel gene therapy strategy for Charcot-Marie-Tooth disease type 2D K. H. Morelli, J. S. Domire, N. Pyne, S. Harper, R. Burgess P34 Molecular regulation of chondrogenic human induced pluripotent stem cells M. A. Gari, A. Dallol, H. Alsehli, A. Gari, M. Gari, A. Abuzenadah P35 Molecular profiling of hematologic malignancies: implementation of a variant assessment algorithm for next generation sequencing data analysis and clinical reporting M. Thomas, M. Sukhai, S. Garg, M. Misyura, T. Zhang, A. Schuh, T. Stockley, S. Kamel-Reid P36 Accessing genomic evidence for clinical variants at NCBI S. Sherry, C. Xiao, D. Slotta, K. Rodarmer, M. Feolo, M. Kimelman, G. Godynskiy, C. O’Sullivan, E. Yaschenko P37 NGS-SWIFT: a cloud-based variant analysis framework using control-accessed sequencing data from DBGAP/SRA C. Xiao, E. Yaschenko, S. Sherry P38 Computational assessment of drug induced hepatotoxicity through gene expression profiling C. Rangel-Escareño, H. Rueda-Zarate P40 Flowr: robust and efficient pipelines using a simple language-agnostic approach;ultraseq; fast modular pipeline for somatic variation calling using flowr S. Seth, S. Amin, X. Song, X. Mao, H. Sun, R. G. Verhaak, A. Futreal, J. Zhang P41 Applying “Big data” technologies to the rapid analysis of heterogenous large cohort data S. J. Whiite, T. Chiang, A. English, J. Farek, Z. Kahn, W. Salerno, N. Veeraraghavan, E. Boerwinkle, R. Gibbs P42 FANTOM5 web resource for the large-scale genome-wide transcription start site activity profiles of wide-range of mammalian cells T. Kasukawa, M. Lizio, J. Harshbarger, S. Hisashi, J. Severin, A. Imad, S. Sahin, T. C. Freeman, K. Baillie, A. Sandelin, P. Carninci, A. R. R. Forrest, H. Kawaji, The FANTOM Consortium P43 Rapid and scalable typing of structural variants for disease cohorts W. Salerno, A. English, S. N. Shekar, A. Mangubat, J. Bruestle, E. Boerwinkle, R. A. Gibbs P44 Polymorphism of glutathione S-transferases and sulphotransferases genes in an Arab population A. H. Salem, M. Ali, A. Ibrahim, M. Ibrahim P46 Genetic divergence of CYP3A5*3 pharmacogenomic marker for native and admixed Mexican populations J. C. Fernandez-Lopez, V. Bonifaz-Peña, C. Rangel-Escareño, A. Hidalgo-Miranda, A. V. Contreras P47 Whole exome sequence meta-analysis of 13 white blood cell, red blood cell, and platelet traits L. Polfus, CHARGE and NHLBI Exome Sequence Project Working Groups P48 Association of adipoq gene with type 2 diabetes and related phenotypes in african american men and women: The jackson heart study S. Davis, R. Xu, S. Gebeab, P Riestra, A Gaye, R. Khan, J. Wilson, A. Bidulescu P49 Common variants in casr gene are associated with serum calcium levels in koreans S. H. Jung, N. Vinayagamoorthy, S. H. Yim, Y. J. Chung P50 Inference of multiple-wave population admixture by modeling decay of linkage disequilibrium with multiple exponential functions Y. Zhou, S. Xu P51 A Bayesian framework for generalized linear mixed models in genome-wide association studies X. Wang, V. Philip, G. Carter P52 Targeted sequencing approach for the identification of the genetic causes of hereditary hearing impairment A. A. Abuzenadah, M. Gari, R. Turki, A. Dallol P53 Identification of enhancer sequences by ATAC-seq open chromatin profiling A. Uyar, A. Kaygun, S. Zaman, E. Marquez, J. George, D. Ucar P54 Direct enrichment for the rapid preparation of targeted NGS libraries C. L. Hendrickson, A. Emerman, D. Kraushaar, S. Bowman, N. Henig, T. Davis, S. Russello, K. Patel P56 Performance of the Agilent D5000 and High Sensitivity D5000 ScreenTape assays for the Agilent 4200 Tapestation System R. Nitsche, L. Prieto-Lafuente P57 ClinVar: a multi-source archive for variant interpretation M. Landrum, J. Lee, W. Rubinstein, D. Maglott P59 Association of functional variants and protein physical interactions of human MUTY homolog linked with familial adenomatous polyposis and colorectal cancer syndrome Z. Abduljaleel, W. Khan, F. A. Al-Allaf, M. Athar , M. M. Taher, N. Shahzad P60 Modification of the microbiom constitution in the gut using chicken IgY antibodies resulted in a reduction of acute graft-versus-host disease after experimental bone marrow transplantation A. Bouazzaoui, E. Huber, A. Dan, F. A. Al-Allaf, W. Herr, G. Sprotte, J. Köstler, A. Hiergeist, A. Gessner, R. Andreesen, E. Holler P61 Compound heterozygous mutation in the LDLR gene in Saudi patients suffering severe hypercholesterolemia F. Al-Allaf, A. Alashwal, Z. Abduljaleel, M. Taher, A. Bouazzaoui, H. Abalkhail, A. Al-Allaf, R. Bamardadh, M. Atha

    GENOMIC SIGNATURES OF ADAPTIVE EVOLUTION

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    Comparative genomics has revolutionized virtually all fields of biology including the study of evolution. In this dissertation, I used next-generation sequencing to explore the evolutionary histories and adaptive evolution of a diverse set of taxa. Comparisons ranged across time scales, from population-level genetic diversity studies to questions spanning the deepest branches of the metazoan lineage. Whole genome sequencing of 50 unrelated Korean individuals revealed that Koreans have a distinct genetic history from the Chinese and Japanese populations. Our Korean-specific variome database was used to identify novel disease-causing variants in the Korean population, highlighting the value of high-quality ethnic variation databases for the accurate interpretation of individual genomes and genetic variations. Using multi-species comparative genomics of mammals, I identified signatures of high-altitude adaptation in the endangered long-tailed goral (Naemorhedus caudatus) in the mountains of Korea, and in a separate study in three species of closely-related montane guinea pigs in the Andes of South America. Phylogenomic analyses were used to confirm that the source species of the domestic guinea pig (Cavia porcellus) was the high-altitude species Cavia tschudii, not the lowland Cavia aperea. Finally, the first jellyfish (Nemopilema nomurai) and shark (Rhinocodon typus) genomes were assembled and used to identify genetic features unique to those lineages. Large scale genomic comparisons of over 80 metazoans revealed correlations between a number of physiological and genetic traits. Taken together, this dissertation shows the power of comparative genomics to address fundamental biological questions across evolutionary time and diverse non-model systems

    Pig Genomics and Genetics

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    In this Special Issue, we present the state of the art in the field of pig genetics and genomics, including the identification of gene candidates linked to important pig traits and to nutritional modifications, with the aim of collecting the most recent advances. The published manuscripts focused on high-throughput methodologies, such as RNA sequencing, ATAC-seq, MACE-seq, chip-seq, and RRBS, and covered other fields of pig genetics. The pig (Sus scrofa) is the most common large mammal in the world. The Sus genus includes domestic pig and wild boar. Since the draft reference genome sequence of S. scrofa was assembled in 2012, the processes of identification of genes related to important phenotypic traits and of search of genetic markers for pig selection have been significantly refined. In addition, the newest wide-range high-throughput techniques, including microarrays, next-generation sequencing, and the recent PacBio sequencing platform providing ultra-long sequencing reads, allow identifying gene mutations and gene candidates throughout the whole genome, transcriptome, or epigenome and estimating quantitative traits important for breeding as well as the genetic backgrounds of inherited diseases

    Evolution of Animal Microbial Communities in Response to Environmental Stress

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    info:eu-repo/semantics/publishedVersio

    Ocular and systemic vascular alterations in overweight and obese individuals undergoing weight-loss interventions

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    Obesity and its accompanying comorbidities play a crucial role in the pathogenesis of endothelial function which is a pre-cursor to atherosclerosis, subsequently leading to increases in cardiovascular risk. However, amelioration of these risk factors and improvements in endothelial function have never been fully explored in functional assessments of the retinal and peripheral microcirculations.The aim of this thesis was therefore to investigate the presence and impact of weight-loss interventions in overweight and obese individuals and also the relationships between functional measurements of different vascular beds. The principle findings of this work were:1. The relationship between retinal and peripheral vascular function in healthy individuals with low cardiovascular risk• Participants with higher peripheral vascular reactivity indices had a higher amplitude change from maximum to minimum and also showed enhanced reaction times to flicker provocation, which correlated to the degree of peripheral vascular function. 2. The effects of physical training on retinal and systemic microvascular function• Physical exercise positively influenced the retinal microcirculation through improvements in dilation and constriction reaction times to flicker provocation. 3. The long-lasting effects of fasting during the month of Ramadan on retinal and peripheral vascular function• Participants during fasting had a higher capacity to reach maximum dilation and also a greater percentage increase from baseline diameters. The retinal veins were also significantly less variable during baseline corrected measurements. 4. The effect of bariatric surgery on retinal vessels structure and systemic microvascular function• Increases were recorded for the diameter of retinal arteries but also for the veins. Peripheral vascular function was significantly improved and arterial stiffness was decreased. CVD risk was significantly decreased and also correlated with retinal vessel calibre measurements. 5. Is there an improvement in anterior ocular health after bariatric surgery?• Anterior surface health doesn’t necessarily cause ocular health problems in obese individuals nor can it be improved or ameliorated through bariatric surger

    The genetic background of five canine models of rare human disease

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    This thesis addresses the genetic background of five spontaneous canine models of rare human disease. By utilizing genome-wide mapping methods, next-generation sequencing analyses and variant validation combined with detailed clinical and post-mortem examinations, we characterized new canine models, identified novel disease-associated variants and dissected their effects on health and morphology. In Study I, next-generation sequencing analysis in a Central Asian Shepherd dog affected by epidermolysis bullosa revealed a nonsense variant in COL7A1. Validation of the variant in 190 dogs confirmed the disease type as recessive dystrophic epidermolysis bullosa. Immunohistochemical stainings in skin samples illustrated the lack of full-length type VII collagen protein in the affected dog. In Study II, genome-wide association analysis combined with next-generation sequence analysis identified a locus and candidate variant associated with recessive pituitary dwarfism in Karelian Bear Dogs. A splice site variant in POU1F1 was confirmed with validation in over 8000 dogs. Computational predictions indicated weakening of the splice acceptor site at the affected intron-exon junction. In Study III, homozygosity mapping combined with next-generation sequence analysis identified candidate regions and variants associated with recessive congenital hearing loss in Rottweilers. A missense variant in LOXHD1 was confirmed with validation in over 800 000 dogs, revealing a link between the variant and Rottweiler breed background. In Study IV, variant screening combined with clinical examinations and statistical analyses revealed novel morphological consequences of a previously described variant in DVL2. The findings showed that the variant is involved in variable caudal vertebral anomalies and contributes to a brachycephalic phenotype. Varying allele frequencies were identified across populations, indicating the differential impact of the variant on the genetic health of dog breeds. In Study V, clinical and post-mortem examinations revealed malignant polymorphic ventricular arrhythmia and sudden cardiac death in young Leonberger dogs. The high prevalence of the disorder in litters and families strongly indicated a genetic aetiology. However, genome-wide association analyses failed to reveal associated loci, likely due to genetic or phenotypic heterogeneity. Future studies aim to overcome these obstacles with expanded cohorts and improved clinical and molecular phenotypes. Our findings have multiple scientific and practical implications. The discoveries facilitate diagnostics and treatment by revealing the molecular and pathophysiological mechanisms of the disorders. Affected dogs also provide novel large animal models for preclinical studies, benefitting both human and veterinary medicine. Finally, the development of gene tests support dog owners and breeders in revising breeding programmes to improve the health of dog breeds.Tässä väitöskirjatyössä selvitettiin viiden koirilla esiintyvän perinnöllisen sairauden taustaa. Tutkimuksissa käytettiin genominlaajuista assosiaatioanalyysiä, seuraavan sukupolven sekvensointianalyysiä ja geneettisten varianttien validaatiota yhdessä yksityiskohtaisten kliinisten ja patologisten tutkimusten kanssa. Työn tuloksena kuvattiin uusia koirilla esiintyviä sairauksia ja tunnistettiin sairauksia aiheuttavia geenimuunnoksia ja niiden vaikutuksia koirien terveyteen ja ruumiinrakenteeseen. Osatyössä I tunnistettiin seuraavan sukupolven sekvensointianalyysillä keskiaasiankoirien epidermolysis bullosa -ihosairauteen liittyvä ehdokasgeenivirhe COL7A1-geenissä. Geenivirheen yhteys sairauteen varmennettiin 190 koiran perimässä, ja sairauden alatyypiksi tarkennettiin resessiivinen dystrofinen epidermolysis bullosa. Immunohistokemialliset värjäykset ihonäytteissä paljastivat täyspitkän kollageeni VII -proteiinin puutoksen sairastuneen koiran ihossa. Osatyössä II tunnistettiin genominlaajuista assosiaatioanalyysiä ja seuraavan sukupolven sekvensointianalyysiä käyttäen karjalankarhukoirien aivolisäkeperäiseen lyhytkasvuisuuteen liittyvä perimän alue ja ehdokasgeenivirhe. POU1F1-geenin silmukointialueella sijaitsevan geenivirheen yhteys sairauteen varmennettiin yli 8000 koiran perimässä. Laskennallinen ennuste viittasi geenivirheen sisältävän introni-eksoni -liitoksen silmukointialueen heikentymiseen. Osatyössä III tunnistettiin homotsygotiakartoitusta ja seuraavan sukupolven sekvensointianalyysiä käyttäen rottweilerien synnynnäiseen kuurouteen liittyviä perimän ehdokasalueita ja -geenivirheitä. LOXHD1-geenissä sijaitsevan geenivirheen yhteys sairauteen varmennettiin yli 800 000 koiran perimässä. Varmennus paljasti myös geenivirheen esiintyvän lähes yksinomaan rottweiler-taustaisissa koirissa. Osatyössä IV tarkennettiin varianttiseulontaa, kliinisiä tutkimuksia ja tilastoanalyysejä käyttäen aiemmin kuvatun DVL2-geenivirheen vaikutuksia koirien ruumiinrakenteeseen. Tulokset osoittivat geenivirheen yhteyden erilaisiin kaudaalinikamien epämuodostumiin ja kuonon pituuden lyhenemiseen. Vaihteleva frekvenssi osoitti geenivirheeseen liittyvien terveysongelmien kuorman eroavan rotujen välillä. Osatyössä V tunnistettiin kliinisiä ja patologisia tutkimuksia käyttäen pahanlaatuisia kammiorytmihäiriöitä ja äkillisiä sydänperäisiä kuolemia nuorissa leonberginkoirissa. Sairauden korkea esiintyvyys pentueittain ja suvuittain viittasi perinnölliseen taustaan, mutta genominlaajuista analyysiä käyttäen ei tunnistettu ehdokasalueita perimästä. Tämä johtui todennäköisesti geneettisestä tai fenotyyppisestä heterogeniasta, mikä pyritään tulevissa analyyseissä huomioimaan suuremmalla otoskoolla ja tarkemmilla kliinisillä ja molekyylitason tutkimuksilla. Väitöstyön tuloksilla on useita tieteellisiä ja käytännön vaikutuksia. Löydökset edistävät diagnostiikkaa ja hoidon kehittämistä paljastamalla sairauksien taustalla olevat molekyylitason patofysiologiset mekanismit. Sairastuneet koirat voivat toimia mallieläiminä prekliinisissä tutkimuksissa, mikä hyödyttää sekä ihmis- että eläinlääketiedettä. Löydöksiin perustuvat geenitestit tukevat lisäksi koiranomistajia ja -kasvattajia jalostussuunnitelmien kehittämisessä terveempään suuntaan

    Integrating Human Population Genetics And Genomics To Elucidate The Etiology Of Brain Disorders

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    Brain disorders present a significant burden on affected individuals, their families and society at large. Existing diagnostic tests suffer from a lack of genetic biomarkers, particularly for substance use disorders, such as alcohol dependence (AD). Numerous studies have demonstrated that AD has a genetic heritability of 40-60%. The existing genetics literature of AD has primarily focused on linkage analyses in small family cohorts and more recently on genome-wide association analyses (GWAS) in large case-control cohorts, fueled by rapid advances in next generation sequencing (NGS). Numerous AD-associated genomic variations are present at a common frequency in the general population, making these variants of public health significance. However, known AD-associated variants explain only a fraction of the expected heritability. In this dissertation, we demonstrate that systems biology applications that integrate evolutionary genomics, rare variants and structural variation can dissect the genetic architecture of AD and elucidate its heritability. We identified several complex human diseases, including AD and other brain disorders, as potential targets of natural selection forces in diverse world populations. Further evidence of natural selection forces affecting AD was revealed when we identified an association between eye color, a trait under strong selection, and AD. These findings provide strong support for conducting GWAS on brain disorder phenotypes. However, with the ever-increasing abundance of rare genomic variants and large cohorts of multi-ethnic samples, population stratification becomes a serious confounding factor for GWAS. To address this problem, we designed a novel approach to identify ancestry informative single nucleotide polymorphisms (SNPs) for population stratification adjustment in association analyses. Furthermore, to leverage untyped variants from genotyping arrays – particularly rare variants – for GWAS and meta-analysis through rapid imputation, we designed a tool that converts genotype definitions across various array platforms. To further elucidate the genetic heritability of brain disorders, we designed approaches aimed at identifying Copy Number Variations (CNVs) and viral insertions into the human genome. We conducted the first CNV-based whole genome meta-analysis for AD. We also designed an integrated approach to estimate the sensitivity of NGS-based methods of viral insertion detection. For the first time in the literature, we identified herpesvirus in NGS data from an Alzheimer’s disease brain sample. The work in this dissertation represents a three-faceted advance in our understanding of brain disease etiology: 1) evolutionary genomic insights, 2) novel resources and tools to leverage rare variants, and 3) the discovery of disease-associated structural genomic aberrations. Our findings have broad implications on the genetics of complex human disease and hold promise for delivering clinically useful knowledge and resources
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