Resultants in genetic Linkage Analysis - Ingileif B. Hallgrímsdóttir; Bernd Sturmfels
Statistical models for genetic linkage analysis of k locus diseases are k-dimensional subvarieties of a (3 k − 1)-dimensional probability simplex. We determine the algebraic invariants of these models with general characteristics for k = 1 and k = 2. In particular we recover, and generalize, the Hardy-Weinberg curve. For k = 2, the invariants are presented as determinants of 32 × 32-matrices of linear forms in 9 unknowns, a suitable format for computations with numerical data.
Genetic divergence among sympatric populations of three species of oyster drills (Urosalpinx) in Cedar Key, Florida - Robinson, John D.; Dillon, Robert T.
Three gastropod species of the genus Urosalpinx inhabit intertidal and subtidal regions of the southeastern United States. Urosalpinx cinerea (Say, 1822) is native to the Atlantic coast from Newfoundland to northeast Florida, while Urosalpinx perrugata (Conrad, 1846) and Urosalpinx tampaensis (Conrad, 1846) are largely restricted to the Gulf of Mexico. The morphological similarity of U. cinerea and U. perrugata is so striking that they have been suggested to be subspecies. We used a combination of molecular and morphological methods to examine divergence among populations of these three nominal species in a newly discovered area of sympatry: Cedar Key, Florida. Significant...
Variability and inheritance of peach SSR sequences - Sánchez-Pérez, Raquel; Dicenta, Federico; Ruiz, C.; Ballester, J.; Arús, Pere; Martínez-Gómez, Pedro
[EN] Variability and inheritance of six peach [Prunus persica (L.) Batsch] SSR (simple-sequence repeat)
markers was studied in 21 almond [P. dulcis (Mill.) D.A. Webb] cultivars and in a progeny of 180 descendants
from the cross between the French cultivar 'R1000' and the Spanish cultivar 'Desmayo Largueta'. The results
showed the molecular identification of the 21 cultivars using the six SSR polymorphic sequences. The number of
alleles revealed by the SSR analysis ranged from 4 to 13, with a high level of heterozygosity. A codominant
segregation of the SSRs was observed in this progeny. These results establish the value of SSR markers for
distinguishing different genetic...
[en] FORECASTING GEOPHYSICAL MEASUREMENTS: PSEUDO-WELLS - SAMUEL GUSTAVO HUAMAN BUSTAMANTE
[pt] No presente trabalho de tese é apresentado, analisado e avaliado um método inédito para prever perfis de poço (para um pseudo-poço), a partir de informações dos poços verticais vizinhos e dados de sísmica 3D. Este método é formado por quatro partes principais. Na primeira parte são processados os perfis de raio gama dos poços para produzir um conjunto de sinais estratificados. Estes resultados são utilizados na segunda parte para realizar a correlação lateral de poços, com um método baseado em Algoritmos Genéticos, cujos resultados são intervalos de estratos semelhantes que indicariam a existência de estruturas rochosas contínuas na subsuperfície....
Syndromes associated with mitochondrial DNA depletion - Nogueira, Célia; Almeida, Ligia S; Nesti, Claudia; Pezzini, Ilaria; Videira, Arnaldo; Vilarinho, Laura; Santorelli, Filippo M
Mitochondrial dysfunction accounts for a large group of inherited metabolic disorders most of which are due to a dysfunctional mitochondrial respiratory chain (MRC) and, consequently, deficient energy production. MRC function depends on the coordinated expression of both nuclear (nDNA) and mitochondrial (mtDNA) genomes. Thus, mitochondrial diseases can be caused by genetic defects in either the mitochondrial or the nuclear genome, or in the cross-talk between the two. This impaired cross-talk gives rise to so-called nuclear-mitochondrial intergenomic communication disorders, which result in loss or instability of the mitochondrial genome and, in turn, impaired maintenance of qualitative and quantitative mtDNA integrity. In...
Polymorphisms in the XRCC1 gene modify survival of bladder cancer patients treated with chemotherapy - Sacerdote, Carlotta; Guarrera, Simonetta; Ricceri, Fulvio; Pardini, Barbara; Polidoro, Silvia; Allione, Alessandra; Critelli, Rossana; Russo, Alessia; Andrew, Angeline S.; Ye, Yuanqing; Wu, Xifeng; Kiemeney, Lambertus A.; Bosio, Andrea; Casetta, Giovanni; Cucchiarale, Giuseppina; Destefanis, Paolo; Gontero, Paolo; Rolle, Luigi; Zitella, Andrea; Fontana, Dario; Vineis, Paolo; Matullo, Giuseppe
Survival of bladder cancer patients depends on several factors including disease stage and grade at diagnosis, age, health status of the patient and the applied treatment. Several studies investigated the role of DNA repair genetic variants in cancer susceptibility, but only few studies investigated their role in survival and response to chemotherapy for bladder cancer. We genotyped 28 single nucleotide polymorphisms (SNP) in DNA repair genes in 456 bladder cancer patients, reconstructed haplotypes and calculated a score for combinations of the SNPs. We estimated Hazard Ratios (adjHR) for time to death. Among patients treated with chemotherapy, variant alleles of five...
Prognostic significance of 2-hydroxyglutarate levels in acute myeloid leukemia in China - Wang, Jiang-Han; Chen, Wen-Lian; Li, Jun-Min; Wu, Song-Fang; Chen, Tian-Lu; Zhu, Yong-Mei; Zhang, Wei-Na; Li, Yang; Qiu, Yun-Ping; Zhao, Ai-Hua; Mi, Jian-Qing; Jin, Jie; Wang, Yun-Gui; Ma, Qiu-Ling; Huang, He; Wu, De-Pei; Wang, Qin-Rong; Li, Yan; Yan, Xiao-Jing; Yan, Jin-Song; Li, Jian-Yong; Wang, Shuai; Huang, Xiao-Jun; Wang, Bing-Shun; Jia, Wei; Shen, Yang; Chen, Zhu; Chen, Sai-Juan
Acute myeloid leukemia (AML) consists of a group of hematopoietic malignancies with considerable diversities in clinical and biological features. Recently, not only genetic abnormalities but also “oncometabolites,” such as 2-hydroxyglutarate (2-HG), have been found to play a role in driving AML pathogenesis and serve as potential disease markers. In this study on a large cohort of AML, we found that the serum 2-HG level was increased in 62 of 367 (17%) cases with distinct hematologic and biological features. Survival analysis performed in 234 patients without prognostic cytogenetic markers showed that increased 2-HG level was a poor predictor, demonstrating the potential...
Convergence in feeding posture occurs through different genetic loci in independently evolved cave populations of Astyanax mexicanus - Kowalko, Johanna E.; Rohner, Nicolas; Linden, Tess A.; Rompani, Santiago B.; Warren, Wesley C.; Borowsky, Richard; Tabin, Clifford J.; Jeffery, William R.; Yoshizawa, Masato
Relatively little is known about the genetic basis of behavioral evolution, in particular for behaviors without any obvious related morphological changes. We have focused on changes in feeding posture that evolved in the small tetra Astyanax mexicanus as it adapted from life in the rivers to the very different ecological conditions found in caves. Using comparative quantitative genetics/genomics, we find that behavioral differences in feeding posture between surface and cave populations arose independently, through different polygenic genetic mechanisms in multiple, independent cave populations. This work provides insights into the genetic architecture of this behavioral trait and shows that this hard-wired...
A cytochrome P450 regulates a domestication trait in cultivated tomato - Chakrabarti, Manohar; Zhang, Na; Sauvage, Christopher; Muños, Stéphane; Blanca, Jose; Cañizares, Joaquin; Diez, Maria Jose; Schneider, Rhiannon; Mazourek, Michael; McClead, Jammi; Causse, Mathilde; van der Knaap, Esther
This study reports the cloning of a tomato gene, SlKLUH, that controls fruit mass by increased cell layers and delayed fruit ripening. In addition, we identified a potential regulatory SNP in the promoter of SlKLUH that is significantly associated with the fruit mass. Altogether, our study encompasses several genetic analyses, as well as association mapping, plant transformation experiments, and phenotypic evaluations to offer insights into the molecular basis of the regulation of tomato fruit mass, a critical trait in the domestication of fruit and vegetable crops.
Dysregulated NOD2 predisposes SAMP1/YitFc mice to chronic intestinal inflammation - Corridoni, Daniele; Kodani, Tomohiro; Rodriguez-Palacios, Alexander; Pizarro, Theresa T.; Xin, Wei; Nickerson, Kourtney P.; McDonald, Christine; Ley, Klaus F.; Abbott, Derek W.; Cominelli, Fabio
We discovered that SAMP1/YitFc (SAMP) mice, which develop spontaneous Crohn’s disease (CD)-like ileitis in the absence of nucleotide-binding oligomerization domain-containing 2 (NOD2) genetic mutations, fail to respond to muramyl dipeptide and display impaired bacterial clearance. These results support the concept that a dysregulated NOD2 in SAMP mice predisposes them to chronic intestinal inflammation. We believe that our study provides a paradigm shift by demonstrating that CD-like ileitis is caused by an innate immune defect, rather than an overly aggressive adaptive immune response. Therefore, preventive and curative treatments for CD should be directed to boost, rather than suppress, mucosal innate immune...
Genetic topography of brain morphology - Chen, Chi-Hua; Fiecas, Mark; Gutiérrez, E. D.; Panizzon, Matthew S.; Eyler, Lisa T.; Vuoksimaa, Eero; Thompson, Wesley K.; Fennema-Notestine, Christine; Hagler, Donald J.; Jernigan, Terry L.; Neale, Michael C.; Franz, Carol E.; Lyons, Michael J.; Fischl, Bruce; Tsuang, Ming T.; Dale, Anders M.; Kremen, William S.
How diverse functional cortical regions develop is an important neuroscience question. Animal experiments show that regional differentiation is controlled by genes that express in a graded and regionalized pattern; however, such investigation in humans is scarce. Using noninvasive imaging techniques to acquire brain structure data of genetically related subjects (i.e., twins), we estimated the spatial pattern of genetic influences on cortical structure. We developed a genetic parcellation of cortical thickness to delineate the boundaries of cortical divisions that are—within each division—maximally under control of shared genetic influences. We also found differences in genetic influences on cortical surface area and thickness...
Invadolysin, a conserved lipid-droplet-associated metalloproteinase, is required for mitochondrial function in Drosophila - Di Cara, Francesca; Duca, Edward; Dunbar, Donald R.; Cagney, Gerard; Heck, Margarete M. S.
Mitochondria are the main producers of ATP, the principal energy source of the cell, and reactive oxygen species (ROS), important signaling molecules. Mitochondrial morphogenesis and function depend on a hierarchical network of mechanisms in which proteases appear to be center stage. The invadolysin gene encodes an essential conserved metalloproteinase of the M8 family that is necessary for mitosis and cell migration during Drosophila development. We previously demonstrated that invadolysin is found associated with lipid droplets in cells. Here, we present data demonstrating that invadolysin interacts physically with three mitochondrial ATP synthase subunits. Our studies have focused on the genetic phenotypes...
Dynein light chain interaction with the peroxisomal import docking complex modulates peroxisome biogenesis in yeast - Chang, Jinlan; Tower, Robert J.; Lancaster, David L.; Rachubinski, Richard A.
Dynein is a large macromolecular motor complex that moves cargo along microtubules. A motor-independent role for the light chain of dynein, Dyn2p, in peroxisome biology in Saccharomyces cerevisiae was suggested from its interaction with Pex14p, a component of the peroxisomal matrix protein import docking complex. Here we show that cells of the yeast Yarrowia lipolytica deleted for the gene encoding the homologue of Dyn2p are impaired in peroxisome function and biogenesis. These cells exhibit compromised growth on medium containing oleic acid as the carbon source, the metabolism of which requires functional peroxisomes. Their peroxisomes have abnormal morphology, atypical matrix protein...
Dbf4: The whole is greater than the sum of its parts - Matthews, Lindsay A.; Guarné, Alba
Together with cyclin-dependent kinases, the Dbf4-dependent kinase (DDK) is essential to activate the Mcm2-7 helicase and, hence, initiate DNA replication in eukaryotes. Beyond its role as the regulatory subunit of the DDK complex, the Dbf4 protein also regulates the activity of other cell cycle kinases to mediate the checkpoint response and prevent premature mitotic exit under stress. Two features that are unusual in DNA replication proteins characterize Dbf4. The first is its evolutionary divergence; the second is how its conserved motifs are combined to form distinct functional units. This structural plasticity appears to be at odds with the conserved functions...
Loci influencing blood pressure identified using a cardiovascular gene-centric array - Ganesh, Santhi K.; Tragante, Vinicius; Guo, Wei; Guo, Yiran; Lanktree, Matthew B.; Smith, Erin N.; Johnson, Toby; Castillo, Berta Almoguera; Barnard, John; Baumert, Jens; Chang, Yen-Pei Christy; Elbers, Clara C.; Farrall, Martin; Fischer, Mary E.; Franceschini, Nora; Gaunt, Tom R.; Gho, Johannes M.I.H.; Gieger, Christian; Gong, Yan; Isaacs, Aaron; Kleber, Marcus E.; Leach, Irene Mateo; McDonough, Caitrin W.; Meijs, Matthijs F.L.; Mellander, Olle; Molony, Cliona M.; Nolte, Ilja M.; Padmanabhan, Sandosh; Price, Tom S.; Rajagopalan, Ramakrishnan; Shaffer, Jonathan; Shah, Sonia; Shen, Haiqing; Soranzo, Nicole; van der Most, Peter J.; Van Iperen, Erik P.A.; Van Setten, Jessic A.; Vonk, Judith M.; Zhang, Li; Beitelshees, Amber L.; Berenson, Gerald S.; Bhatt, Deepak L.; Boer, Jolanda M.A.; Boerwinkle, Eric; Burkley, Ben; Burt, Amber; Chakravarti, Aravinda; Chen, Wei; Cooper-DeHoff, Rhonda M.; Curtis, Sean P.; Dreisbach, Albert; Duggan, David; Ehret, Georg B.; Fabsitz, Richard R.; Fornage, Myriam; Fox, Ervin; Furlong, Clement E.; Gansevoort, Ron T.; Hofker, Marten H.; Hovingh, G. Kees; Kirkland, Susan A.; Kottke-Marchant, Kandice; Kutlar, Abdullah; LaCroix, Andrea Z.; Langaee, Taimour Y.; Li, Yun R.; Lin, Honghuang; Liu, Kiang; Maiwald, Steffi; Malik, Rainer; ; Murugesan, Gurunathan; Newton-Cheh, Christopher; O'Connell, Jeffery R.; Onland-Moret, N. Charlotte; Ouwehand, Willem H.; Palmas, Walter; Penninx, Brenda W.; Pepine, Carl J.; Pettinger, Mary; Polak, Joseph F.; Ramachandran, Vasan S.; Ranchalis, Jane; Redline, Susan; Ridker, Paul M.; Rose, Lynda M.; Scharnag, Hubert; Schork, Nicholas J.; Shimbo, Daichi; Shuldiner, Alan R.; Srinivasan, Sathanur R.; Stolk, Ronald P.; Taylor, Herman A.; Thorand, Barbara; Trip, Mieke D.; van Duijn, Cornelia M.; Verschuren, W. Monique; Wijmenga, Cisca; Winkelmann, Bernhard R.; Wyatt, Sharon; Young, J. Hunter; Boehm, Bernhard O.; Caulfield, Mark J.; Chasman, Daniel I.; Davidson, Karina W.; Doevendans, Pieter A.; FitzGerald, Garret A.; Gums, John G.; Hakonarson, Hakon; Hillege, Hans L.; Illig, Thomas; Jarvik, Gail P.; Johnson, Julie A.; Kastelein, John J.P.; Koenig, Wolfgang; ; März, Winfried; Mitchell, Braxton D.; Murray, Sarah S.; Oldehinkel, Albertine J.; Rader, Daniel J.; Reilly, Muredach P.; Reiner, Alex P.; Schadt, Eric E.; Silverstein, Roy L.; Snieder, Harold; Stanton, Alice V.; Uitterlinden, André G.; van der Harst, Pim; van der Schouw, Yvonne T.; Samani, Nilesh J.; Johnson, Andrew D.; Munroe, Patricia B.; de Bakker, Paul I.W.; Zhu, Xiaofeng; Levy, Daniel; Keating, Brendan J.; Asselbergs, Folkert W.
Blood pressure (BP) is a heritable determinant of risk for cardiovascular disease (CVD). To investigate genetic associations with systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP) and pulse pressure (PP), we genotyped ∼50 000 single-nucleotide polymorphisms (SNPs) that capture variation in ∼2100 candidate genes for cardiovascular phenotypes in 61 619 individuals of European ancestry from cohort studies in the USA and Europe. We identified novel associations between rs347591 and SBP (chromosome 3p25.3, in an intron of HRH1) and between rs2169137 and DBP (chromosome1q32.1 in an intron of MDM4) and between rs2014408 and SBP (chromosome 11p15 in an intron...
Gene regulatory networks governing pancreas development - Arda, H. Efsun; Benitez, Cecil; Kim, Seung K.
Elucidation of cellular and gene regulatory networks (GRNs) governing organ development will accelerate progress toward tissue replacement. Here, we have compiled reference GRNs underlying pancreas development from data mining that integrates multiple approaches including mutant analysis, lineage tracing, cell purification, gene expression and enhancer analysis, and biochemical studies of gene regulation. Using established computational tools, we integrated and represented these networks into frameworks that should enhance understanding of the surging output of genomic-scale genetic and epigenetic studies of pancreas development and diseases like diabetes and pancreatic cancer. We envision similar approaches would be useful for understanding development of other organs.
Genetic ablation of aquaporin-2 in the mouse connecting tubules results in defective renal water handling - Kortenoeven, Marleen L A; Pedersen, Nis Borbye; Miller, R Lance; Rojek, Aleksandra; Fenton, Robert A
Body water balance is regulated via the water channel aquaporin-2 (AQP2), which is expressed in the renal connecting tubule (CNT) and collecting duct (CD). The relative roles of AQP2 in the CNT and CD are not fully understood. To study the role of AQP2 in the CNT we generated a mouse model with CNT-specific AQP2 deletion (AQP2-CNT-knockout (KO)). Confocal laser scanning microscopy and immunogold electron microscopy demonstrated an absence of AQP2 in the CNT of AQP2-CNT-KO mice. Twenty-four hour urine output was significantly increased (KO: 3.0 ± 0.3 ml (20 g body weight (BW))−1; wild-type (WT): 1.9 ± 0.3 ml...
Genetic removal of basal nitric oxide enhances contractile activity in isolated murine collecting lymphatic vessels - Scallan, Joshua P; Davis, Michael J
The role of nitric oxide (NO) in regulating lymphatic contractile function and, consequently, lymph flow has been the subject of intense study. Despite this, the precise effects of NO on lymphatic contractile activity remain unclear. Recent hypotheses posit that basal levels of endogenous NO increase lymphatic contraction strength as a consequence of lowering frequency (i.e. positive lusitropy), whereas higher agonist-evoked concentrations of NO exert purely inhibitory effects on contractile function. We tested both hypotheses directly by isolating and cannulating collecting lymphatic vessels from genetically modified mice for ex vivo study. The effects of basal NO and agonist-evoked NO were evaluated,...