Structural health monitoring (vibration) as a tool for identifying structural alterations of the lumbar spine: a twin control study.

Science.gov (United States)

Kawchuk, Gregory N; Hartvigsen, Jan; Edgecombe, Tiffany; Prasad, Narasimha; van Dieen, Jaap H

2016-03-11

Structural health monitoring (SHM) is an engineering technique used to identify mechanical abnormalities not readily apparent through other means. Recently, SHM has been adapted for use in biological systems, but its invasive nature limits its clinical application. As such, the purpose of this project was to determine if a non-invasive form of SHM could identify structural alterations in the spines of living human subjects. Lumbar spines of 10 twin pairs were visualized by magnetic resonance imaging then assessed by a blinded radiologist to determine whether twin pairs were structurally concordant or discordant. Vibration was then applied to each subject's spine and the resulting response recorded from sensors overlying lumbar spinous processes. The peak frequency, area under the curve and the root mean square were computed from the frequency response function of each sensor. Statistical analysis demonstrated that in twins whose structural appearance was discordant, peak frequency was significantly different between twin pairs while in concordant twins, no outcomes were significantly different. From these results, we conclude that structural changes within the spine can alter its vibration response. As such, further investigation of SHM to identify spinal abnormalities in larger human populations is warranted.

Effect of existing twin boundaries in martensite on the rubber-like behavior and ageing effect in Au-Cd alloys

International Nuclear Information System (INIS)

Murakami, Y.; Nakajima, Y.; Otsuka, K.; Ohba, T.

1995-01-01

The effect of existing twin(or intervariant) boundaries on both the rubber-like behavior and the ageing effect(Af temperature increase) was studied by using γ 2 ' (orthorhombic) and ζ 2 '(trigonal) martensites in Au-Cd alloys. A typical rubber-like behavior was observed even in a single-variant specimen of γ 2 ' martensite, which proves that the presence of twin boundaries is not the necessary condition for the rubber-like behavior. Thus, the previously proposed mechanism for pinning of boundaries was denied. However, the observed Af temperature increase in the ζ 2 ' martensite was more pronounced in the specimen with twin boundaries(multi-variant state) rather than that without twin boundaries(single-variant state). Thus, it was found that the presence of twin boundaries affects the development of ageing effect though it is not the direct origin for the phenomenon. (orig.)

Twinning processes in Cu-Al-Ni martensite single crystals investigated by neutron single crystal diffraction method

International Nuclear Information System (INIS)

Molnar, P.; Sittner, P.; Novak, V.; Lukas, P.

2008-01-01

A neutron single crystal diffraction method for inspecting the quality of martensite single crystals is introduced. True interface-free martensite single crystals are indispensable for, e.g. measurement of elastic constants of phases by ultrasonic techniques. The neutron diffraction method was used to detect and distinguish the presence of individual lattice correspondence variants of the 2H orthorhombic martensite phase in Cu-Al-Ni as well as to follow the activity of twinning processes during the deformation test on the martensite variant single crystals. When preparing the martensite single variant prism-shaped crystals by compression deformation method, typically a small fraction of second unwanted martensitic variant (compound twin) remains in the prism samples. Due to the very low stress (∼1 MPa) for the compound twinning in many shape memory alloys, it is quite difficult not only to deplete the martensite prisms of all internal interfaces but mainly to keep them in the martensite single variant state for a long time needed for further investigations

Identifying noncoding risk variants using disease-relevant gene regulatory networks.

Science.gov (United States)

Gao, Long; Uzun, Yasin; Gao, Peng; He, Bing; Ma, Xiaoke; Wang, Jiahui; Han, Shizhong; Tan, Kai

2018-02-16

Identifying noncoding risk variants remains a challenging task. Because noncoding variants exert their effects in the context of a gene regulatory network (GRN), we hypothesize that explicit use of disease-relevant GRNs can significantly improve the inference accuracy of noncoding risk variants. We describe Annotation of Regulatory Variants using Integrated Networks (ARVIN), a general computational framework for predicting causal noncoding variants. It employs a set of novel regulatory network-based features, combined with sequence-based features to infer noncoding risk variants. Using known causal variants in gene promoters and enhancers in a number of diseases, we show ARVIN outperforms state-of-the-art methods that use sequence-based features alone. Additional experimental validation using reporter assay further demonstrates the accuracy of ARVIN. Application of ARVIN to seven autoimmune diseases provides a holistic view of the gene subnetwork perturbed by the combinatorial action of the entire set of risk noncoding mutations.

Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis

Science.gov (United States)

Beecham, Ashley H; Patsopoulos, Nikolaos A; Xifara, Dionysia K; Davis, Mary F; Kemppinen, Anu; Cotsapas, Chris; Shahi, Tejas S; Spencer, Chris; Booth, David; Goris, An; Oturai, Annette; Saarela, Janna; Fontaine, Bertrand; Hemmer, Bernhard; Martin, Claes; Zipp, Frauke; D’alfonso, Sandra; Martinelli-Boneschi, Filippo; Taylor, Bruce; Harbo, Hanne F; Kockum, Ingrid; Hillert, Jan; Olsson, Tomas; Ban, Maria; Oksenberg, Jorge R; Hintzen, Rogier; Barcellos, Lisa F; Agliardi, Cristina; Alfredsson, Lars; Alizadeh, Mehdi; Anderson, Carl; Andrews, Robert; Søndergaard, Helle Bach; Baker, Amie; Band, Gavin; Baranzini, Sergio E; Barizzone, Nadia; Barrett, Jeffrey; Bellenguez, Céline; Bergamaschi, Laura; Bernardinelli, Luisa; Berthele, Achim; Biberacher, Viola; Binder, Thomas M C; Blackburn, Hannah; Bomfim, Izaura L; Brambilla, Paola; Broadley, Simon; Brochet, Bruno; Brundin, Lou; Buck, Dorothea; Butzkueven, Helmut; Caillier, Stacy J; Camu, William; Carpentier, Wassila; Cavalla, Paola; Celius, Elisabeth G; Coman, Irène; Comi, Giancarlo; Corrado, Lucia; Cosemans, Leentje; Cournu-Rebeix, Isabelle; Cree, Bruce A C; Cusi, Daniele; Damotte, Vincent; Defer, Gilles; Delgado, Silvia R; Deloukas, Panos; di Sapio, Alessia; Dilthey, Alexander T; Donnelly, Peter; Dubois, Bénédicte; Duddy, Martin; Edkins, Sarah; Elovaara, Irina; Esposito, Federica; Evangelou, Nikos; Fiddes, Barnaby; Field, Judith; Franke, Andre; Freeman, Colin; Frohlich, Irene Y; Galimberti, Daniela; Gieger, Christian; Gourraud, Pierre-Antoine; Graetz, Christiane; Graham, Andrew; Grummel, Verena; Guaschino, Clara; Hadjixenofontos, Athena; Hakonarson, Hakon; Halfpenny, Christopher; Hall, Gillian; Hall, Per; Hamsten, Anders; Harley, James; Harrower, Timothy; Hawkins, Clive; Hellenthal, Garrett; Hillier, Charles; Hobart, Jeremy; Hoshi, Muni; Hunt, Sarah E; Jagodic, Maja; Jelčić, Ilijas; Jochim, Angela; Kendall, Brian; Kermode, Allan; Kilpatrick, Trevor; Koivisto, Keijo; Konidari, Ioanna; Korn, Thomas; Kronsbein, Helena; Langford, Cordelia; Larsson, Malin; Lathrop, Mark; Lebrun-Frenay, Christine; Lechner-Scott, Jeannette; Lee, Michelle H; Leone, Maurizio A; Leppä, Virpi; Liberatore, Giuseppe; Lie, Benedicte A; Lill, Christina M; Lindén, Magdalena; Link, Jenny; Luessi, Felix; Lycke, Jan; Macciardi, Fabio; Männistö, Satu; Manrique, Clara P; Martin, Roland; Martinelli, Vittorio; Mason, Deborah; Mazibrada, Gordon; McCabe, Cristin; Mero, Inger-Lise; Mescheriakova, Julia; Moutsianas, Loukas; Myhr, Kjell-Morten; Nagels, Guy; Nicholas, Richard; Nilsson, Petra; Piehl, Fredrik; Pirinen, Matti; Price, Siân E; Quach, Hong; Reunanen, Mauri; Robberecht, Wim; Robertson, Neil P; Rodegher, Mariaemma; Rog, David; Salvetti, Marco; Schnetz-Boutaud, Nathalie C; Sellebjerg, Finn; Selter, Rebecca C; Schaefer, Catherine; Shaunak, Sandip; Shen, Ling; Shields, Simon; Siffrin, Volker; Slee, Mark; Sorensen, Per Soelberg; Sorosina, Melissa; Sospedra, Mireia; Spurkland, Anne; Strange, Amy; Sundqvist, Emilie; Thijs, Vincent; Thorpe, John; Ticca, Anna; Tienari, Pentti; van Duijn, Cornelia; Visser, Elizabeth M; Vucic, Steve; Westerlind, Helga; Wiley, James S; Wilkins, Alastair; Wilson, James F; Winkelmann, Juliane; Zajicek, John; Zindler, Eva; Haines, Jonathan L; Pericak-Vance, Margaret A; Ivinson, Adrian J; Stewart, Graeme; Hafler, David; Hauser, Stephen L; Compston, Alastair; McVean, Gil; De Jager, Philip; Sawcer, Stephen; McCauley, Jacob L

2013-01-01

Using the ImmunoChip custom genotyping array, we analysed 14,498 multiple sclerosis subjects and 24,091 healthy controls for 161,311 autosomal variants and identified 135 potentially associated regions (p-value multiple sclerosis subjects and 26,703 healthy controls. In these 80,094 individuals of European ancestry we identified 48 new susceptibility variants (p-value multiple sclerosis risk variants in 103 discrete loci outside of the Major Histocompatibility Complex. With high resolution Bayesian fine-mapping, we identified five regions where one variant accounted for more than 50% of the posterior probability of association. This study enhances the catalogue of multiple sclerosis risk variants and illustrates the value of fine-mapping in the resolution of GWAS signals. PMID:24076602

Use of a twin dataset to identify AMD-related visual patterns controlled by genetic factors

Science.gov (United States)

Quellec, Gwénolé; Abràmoff, Michael D.; Russell, Stephen R.

2010-03-01

The mapping of genotype to the phenotype of age-related macular degeneration (AMD) is expected to improve the diagnosis and treatment of the disease in a near future. In this study, we focused on the first step to discover this mapping: we identified visual patterns related to AMD which seem to be controlled by genetic factors, without explicitly relating them to the genes. For this purpose, we used a dataset of eye fundus photographs from 74 twin pairs, either monozygotic twins, who have the same genotype, or dizygotic twins, whose genes responsible for AMD are less likely to be identical. If we are able to differentiate monozygotic twins from dizygotic twins, based on a given visual pattern, then this pattern is likely to be controlled by genetic factors. The main visible consequence of AMD is the apparition of drusen between the retinal pigment epithelium and Bruch's membrane. We developed two automated drusen detectors based on the wavelet transform: a shape-based detector for hard drusen, and a texture- and color- based detector for soft drusen. Forty visual features were evaluated at the location of the automatically detected drusen. These features characterize the texture, the shape, the color, the spatial distribution, or the amount of drusen. A distance measure between twin pairs was defined for each visual feature; a smaller distance should be measured between monozygotic twins for visual features controlled by genetic factors. The predictions of several visual features (75.7% accuracy) are comparable or better than the predictions of human experts.

Mechanical twinning and texture evolution in severely deformed Ti-6Al-4V at high temperatures

International Nuclear Information System (INIS)

Yapici, Guney Guven; Karaman, Ibrahim; Luo Zhiping

2006-01-01

We have investigated the deformation behavior and texture evolution of two-phase Ti-6Al-4V subjected to severe plastic deformation using equal channel angular extrusion (ECAE) at a high temperature (∼0.55T m ). Significant deformation twinning activity was observed after one and two ECAE passes in a 90 deg, die at 800 deg. C. Twinning activity at such a high temperature is a first-time observation in this material and is attributed to the high strain and stress levels imposed during ECAE. High stress levels and the stress state can affect the separation of twinning partials considerably. Resolved shear stress magnitudes on twin partials were found to be high during the ECAE process that helps the nucleation of mechanical twinning. The twinning mode was identified as the {101-bar 1} type using electron diffraction patterns which is one of the twinning modes observed in Ti at temperatures above 350 deg. C. Although only one twinning variant was mainly evident after one pass, multiple twin variants of the same mode were observed after the second pass with a significant increase in twin volume fraction. ECAE processing aligned the basal planes of the hexagonal close-packed α phase, initially having a random texture, with the ECAE shear plane. Texture evolution during ECAE was successfully predicted using a viscoplastic self-consistent crystal plasticity framework capturing the effect of the observed twinning mode on texture. Mechanical twins formed during ECAE and grain refinement led to a noteworthy improvement in flow stresses under tension and compression at room temperature. A strong directional anisotropy in yield strengths was also evident which cannot be explained only by crystallographic texture. It was speculated that the asymmetry of critical resolved shear stresses of deformation modes and the processing-induced deformation structure should play a role. With the supporting evidence from our previous works on the severe plastic deformation of other

Whole-genome sequencing of monozygotic twins discordant for schizophrenia indicates multiple genetic risk factors for schizophrenia.

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Tang, Jinsong; Fan, Yu; Li, Hong; Xiang, Qun; Zhang, Deng-Feng; Li, Zongchang; He, Ying; Liao, Yanhui; Wang, Ya; He, Fan; Zhang, Fengyu; Shugart, Yin Yao; Liu, Chunyu; Tang, Yanqing; Chan, Raymond C K; Wang, Chuan-Yue; Yao, Yong-Gang; Chen, Xiaogang

2017-06-20

Schizophrenia is a common disorder with a high heritability, but its genetic architecture is still elusive. We implemented whole-genome sequencing (WGS) analysis of 8 families with monozygotic (MZ) twin pairs discordant for schizophrenia to assess potential association of de novo mutations (DNMs) or inherited variants with susceptibility to schizophrenia. Eight non-synonymous DNMs (including one splicing site) were identified and shared by twins, which were either located in previously reported schizophrenia risk genes (p.V24689I mutation in TTN, p.S2506T mutation in GCN1L1, IVS3+1G > T in DOCK1) or had a benign to damaging effect according to in silico prediction analysis. By searching the inherited rare damaging or loss-of-function (LOF) variants and common susceptible alleles from three classes of schizophrenia candidate genes, we were able to distill genetic alterations in several schizophrenia risk genes, including GAD1, PLXNA2, RELN and FEZ1. Four inherited copy number variations (CNVs; including a large deletion at 16p13.11) implicated for schizophrenia were identified in four families, respectively. Most of families carried both missense DNMs and inherited risk variants, which might suggest that DNMs, inherited rare damaging variants and common risk alleles together conferred to schizophrenia susceptibility. Our results support that schizophrenia is caused by a combination of multiple genetic factors, with each DNM/variant showing a relatively small effect size. Copyright © 2017 Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. All rights reserved.

Incidental copy-number variants identified by routine genome testing in a clinical population

Science.gov (United States)

Boone, Philip M.; Soens, Zachry T.; Campbell, Ian M.; Stankiewicz, Pawel; Cheung, Sau Wai; Patel, Ankita; Beaudet, Arthur L.; Plon, Sharon E.; Shaw, Chad A.; McGuire, Amy L.; Lupski, James R.

2013-01-01

Purpose Mutational load of susceptibility variants has not been studied on a genomic scale in a clinical population, nor has the potential to identify these mutations as incidental findings during clinical testing been systematically ascertained. Methods Array comparative genomic hybridization, a method for genome-wide detection of DNA copy-number variants, was performed clinically on DNA from 9,005 individuals. Copy-number variants encompassing or disrupting single genes were identified and analyzed for their potential to confer predisposition to dominant, adult-onset disease. Multigene copy-number variants affecting dominant, adult-onset cancer syndrome genes were also assessed. Results In our cohort, 83 single-gene copy-number variants affected 40 unique genes associated with dominant, adult-onset disorders and unrelated to the patients’ referring diagnoses (i.e., incidental) were found. Fourteen of these copy-number variants are likely disease-predisposing, 25 are likely benign, and 44 are of unknown clinical consequence. When incidental copy-number variants spanning up to 20 genes were considered, 27 copy-number variants affected 17 unique genes associated with dominant, adult-onset cancer predisposition. Conclusion Copy-number variants potentially conferring susceptibility to adult-onset disease can be identified as incidental findings during routine genome-wide testing. Some of these mutations may be medically actionable, enabling disease surveillance or prevention; however, most incidentally observed single-gene copy-number variants are currently of unclear significance to the patient. PMID:22878507

A de novo Mutation in KMT2A (MLL) in monozygotic twins with Wiedemann-Steiner syndrome.

Science.gov (United States)

Dunkerton, Sophie; Field, Matthew; Cho, Vicki; Bertram, Edward; Whittle, Belinda; Groves, Alexandra; Goel, Himanshu

2015-09-01

Growth deficiency, psychomotor delay, and facial dysmorphism was originally described in a male patient in 1989 by Wiedemann et al. and later in 2000 by Steiner et al. Wiedemann-Steiner syndrome (WSS) has since been described only a few times in the literature, with the phenotypic spectrum both expanding and becoming more delineated with each patient reported. We report on the clinical and molecular features of monozygotic twins with a de novo mutation in KMT2A. Single nucleotide polymorphism (SNP) microarray was done on both twins and whole-exome sequencing was done using both parents and one of the affected twins. SNP microarray confirmed that they were monozygotic twins. A de novo heterozygous variant (p. Arg1083*) in the KMT2A gene was identified through whole-exome sequencing, confirming the diagnosis of WSS. In this study, we have identified a de novo mutation in KMT2A associated with psychomotor developmental delay, facial dysmorphism, short stature, hypertrichosis cubiti, and small kidneys. This finding in monozygotic twins gives specificity to the WSS. The description of more cases of WSS is needed for further delineation of this condition. Small kidneys with normal function have not been described in this condition in the medical literature before. © 2015 Wiley Periodicals, Inc.

Musical Interests and Talent: Twin Jazz Musicians and Twin Studies/Twin Research: Loss of a Preterm Multiple; Conjoined Twin Conception; Depression in Fathers of Twins; Twin-to-Twin Transfusion Syndrome/Twin News: High-Achieving Twins; Twin Children of a Tennis Star; Conjoined Twin Separation; Twin Delivery to a Giant Panda.

Science.gov (United States)

Segal, Nancy L

2017-12-01

Findings from twin studies of musical interests and talent are reviewed as a backdrop to the lives and careers of twin jazz musicians, Peter and Will Anderson. The Anderson twins exemplify many aspects of twin research, namely their matched musical abilities, shared musical interests, and common career. This overview is followed by reviews of studies and case reports of bereavement in families who have lost a preterm multiple birth infant, the conception of conjoined twins following in vitro fertilization (IVF), depression in fathers of twins, and twin-to-twin transfusion incidence in monochorionic-diamniotic IVF twin pairs. Twins highlighted in the media include high-achieving identical female twins with nearly identical academic standing, tennis star Roger Federer's two sets of identical twin children, surgical separation of craniopagus conjoined twins, and the rare delivery of twins to a 23-year-old giant panda.

Exome Genotyping Identifies Pleiotropic Variants Associated with Red Blood Cell Traits

DEFF Research Database (Denmark)

Chami, Nathalie; Chen, Ming-Huei; Slater, Andrew J

2016-01-01

array. After conditional analyses and replication in 27,480 independent individuals, we identified 16 new RBC variants. We found low-frequency missense variants in MAP1A (rs55707100, minor allele frequency [MAF] = 3.3%, p = 2 × 10(-10) for hemoglobin [HGB]) and HNF4A (rs1800961, MAF = 2.4%, p

An elasto-plastic self-consistent model with hardening based on dislocation density, twinning and de-twinning: Application to strain path changes in HCP metals

International Nuclear Information System (INIS)

Zecevic, Milovan; Knezevic, Marko; Beyerlein, Irene J.; Tomé, Carlos N.

2015-01-01

In this work, we develop a polycrystal mean-field constitutive model based on an elastic–plastic self-consistent (EPSC) framework. In this model, we incorporate recently developed subgrain models for dislocation density evolution with thermally activated slip, twin activation via statistical stress fluctuations, reoriented twin domains within the grain and associated stress relaxation, twin boundary hardening, and de-twinning. The model is applied to a systematic set of strain path change tests on pure beryllium (Be). Under the applied deformation conditions, Be deforms by multiple slip modes and deformation twinning and thereby provides a challenging test for model validation. With a single set of material parameters, determined using the flow-stress vs. strain responses during monotonic testing, the model predicts well the evolution of texture, lattice strains, and twinning. With further analysis, we demonstrate the significant influence of internal residual stresses on (1) the flow stress drop when reloading from one path to another, (2) deformation twin activation, (3) de-twinning during a reversal strain path change, and (4) the formation of additional twin variants during a cross-loading sequence. The model presented here can, in principle, be applied to other metals, deforming by multiple slip and twinning modes under a wide range of temperature, strain rate, and strain path conditions

Rare copy number variants identified in prune belly syndrome.

Science.gov (United States)

Boghossian, Nansi S; Sicko, Robert J; Giannakou, Andreas; Dimopoulos, Aggeliki; Caggana, Michele; Tsai, Michael Y; Yeung, Edwina H; Pankratz, Nathan; Cole, Benjamin R; Romitti, Paul A; Browne, Marilyn L; Fan, Ruzong; Liu, Aiyi; Kay, Denise M; Mills, James L

2018-03-01

Prune belly syndrome (PBS), also known as Eagle-Barrett syndrome, is a rare congenital disorder characterized by absence or hypoplasia of the abdominal wall musculature, urinary tract anomalies, and cryptorchidism in males. The etiology of PBS is largely unresolved, but genetic factors are implicated given its recurrence in families. We examined cases of PBS to identify novel pathogenic copy number variants (CNVs). A total of 34 cases (30 males and 4 females) with PBS identified from all live births in New York State (1998-2005) were genotyped using Illumina HumanOmni2.5 microarrays. CNVs were prioritized if they were absent from in-house controls, encompassed ≥10 consecutive probes, were ≥20 Kb in size, had ≤20% overlap with common variants in population reference controls, and had ≤20% overlap with any variant previously detected in other birth defect phenotypes screened in our laboratory. We identified 17 candidate autosomal CNVs; 10 cases each had one CNV and four cases each had two CNVs. The CNVs included a 158 Kb duplication at 4q22 that overlaps the BMPR1B gene; duplications of different sizes carried by two cases in the intron of STIM1 gene; a 67 Kb duplication 202 Kb downstream of the NOG gene, and a 1.34 Mb deletion including the MYOCD gene. The identified rare CNVs spanned genes involved in mesodermal, muscle, and urinary tract development and differentiation, which might help in elucidating the genetic contribution to PBS. We did not have parental DNA and cannot identify whether these CNVs were de novo or inherited. Further research on these CNVs, particularly BMP signaling is warranted to elucidate the pathogenesis of PBS. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Twinning induced by the rhombohedral to orthorhombic phase transition in lanthanum gallate (LaGaO3)

Science.gov (United States)

Wang, W. L.; Lu, H. Y.

2006-10-01

Phase-transformation-induced twins in pressureless-sintered lanthanum gallate (LaGaO3) ceramics have been analysed using the transmission electron microscopy (TEM). Twins are induced by solid state phase transformation upon cooling from the rhombohedral (r, Rbar{3}c) to orthorhombic ( o, Pnma) symmetry at ˜145°C. Three types of transformation twins {101} o , {121} o , and {123} o were found in grains containing multiple domains that represent orientation variants. Three orthorhombic orientation variants were distinguished from the transformation domains converged into a triple junction. These twins are the reflection type as confirmed by tilting experiment in the microscope. Although not related by group-subgroup relation, the transformation twins generated by phase transition from rhombohedral to orthorhombic are consistent with those derived from taking cubic Pm {bar {3}}m aristotype of the lowest common supergroup symmetry as an intermediate metastable structure. The r→ o phase transition of first order in nature may have occurred by a diffusionless, martensitic-type or discontinuous nucleation and growth mechanism.

Rapid-Onset Obesity with Hypothalamic Dysfunction, Hypoventilation, and Autonomic Dysregulation (ROHHAD): exome sequencing of trios, monozygotic twins and tumours.

Science.gov (United States)

Barclay, Sarah F; Rand, Casey M; Borch, Lauren A; Nguyen, Lisa; Gray, Paul A; Gibson, William T; Wilson, Richard J A; Gordon, Paul M K; Aung, Zaw; Berry-Kravis, Elizabeth M; Ize-Ludlow, Diego; Weese-Mayer, Debra E; Bech-Hansen, N Torben

2015-08-25

Rapid-onset Obesity with Hypothalamic Dysfunction, Hypoventilation, and Autonomic Dysregulation (ROHHAD) is thought to be a genetic disease caused by de novo mutations, though causative mutations have yet to be identified. We searched for de novo coding mutations among a carefully-diagnosed and clinically homogeneous cohort of 35 ROHHAD patients. We sequenced the exomes of seven ROHHAD trios, plus tumours from four of these patients and the unaffected monozygotic (MZ) twin of one (discovery cohort), to identify constitutional and somatic de novo sequence variants. We further analyzed this exome data to search for candidate genes under autosomal dominant and recessive models, and to identify structural variations. Candidate genes were tested by exome or Sanger sequencing in a replication cohort of 28 ROHHAD singletons. The analysis of the trio-based exomes found 13 de novo variants. However, no two patients had de novo variants in the same gene, and additional patient exomes and mutation analysis in the replication cohort did not provide strong genetic evidence to implicate any of these sequence variants in ROHHAD. Somatic comparisons revealed no coding differences between any blood and tumour samples, or between the two discordant MZ twins. Neither autosomal dominant nor recessive analysis yielded candidate genes for ROHHAD, and we did not identify any potentially causative structural variations. Clinical exome sequencing is highly unlikely to be a useful diagnostic test in patients with true ROHHAD. As ROHHAD has a high risk for fatality if not properly managed, it remains imperative to expand the search for non-exomic genetic risk factors, as well as to investigate other possible mechanisms of disease. In so doing, we will be able to confirm objectively the ROHHAD diagnosis and to contribute to our understanding of obesity, respiratory control, hypothalamic function, and autonomic regulation.

Effect of Magnetostatic Interactions on Twin Boundary Motion in NiMnGa Magnetic Shape Memory Alloy

DEFF Research Database (Denmark)

Heczko, Oleg; Vokoun, David; Kopecky, Vit

2015-01-01

on the initial position of the twin boundary, the magnetic field providing the critical stress varied in the range 832 kA/m. By taking into account the variants sizes and their mutual interactions, we explained the observed dependence of the switching field on the location of the boundary. The resulting match......We investigated the effect of magnetostatic interactions on the field-induced reorientation of martensite variants in Ni50.0Mn27.5Ga22.5. The reorientation, achieved by sweeping a single Type-II twin boundary along the sample, was triggered by a twinning stress of about 0.1 MPa. However, depending...... between model predictions and measurements illustrates the fundamental role played by demagnetization effects and magnetostatic interactions in magnetic shape memory effect....

Three-dimensional spatial analysis of missense variants in RTEL1 identifies pathogenic variants in patients with Familial Interstitial Pneumonia.

Science.gov (United States)

Sivley, R Michael; Sheehan, Jonathan H; Kropski, Jonathan A; Cogan, Joy; Blackwell, Timothy S; Phillips, John A; Bush, William S; Meiler, Jens; Capra, John A

2018-01-23

Next-generation sequencing of individuals with genetic diseases often detects candidate rare variants in numerous genes, but determining which are causal remains challenging. We hypothesized that the spatial distribution of missense variants in protein structures contains information about function and pathogenicity that can help prioritize variants of unknown significance (VUS) and elucidate the structural mechanisms leading to disease. To illustrate this approach in a clinical application, we analyzed 13 candidate missense variants in regulator of telomere elongation helicase 1 (RTEL1) identified in patients with Familial Interstitial Pneumonia (FIP). We curated pathogenic and neutral RTEL1 variants from the literature and public databases. We then used homology modeling to construct a 3D structural model of RTEL1 and mapped known variants into this structure. We next developed a pathogenicity prediction algorithm based on proximity to known disease causing and neutral variants and evaluated its performance with leave-one-out cross-validation. We further validated our predictions with segregation analyses, telomere lengths, and mutagenesis data from the homologous XPD protein. Our algorithm for classifying RTEL1 VUS based on spatial proximity to pathogenic and neutral variation accurately distinguished 7 known pathogenic from 29 neutral variants (ROC AUC = 0.85) in the N-terminal domains of RTEL1. Pathogenic proximity scores were also significantly correlated with effects on ATPase activity (Pearson r = -0.65, p = 0.0004) in XPD, a related helicase. Applying the algorithm to 13 VUS identified from sequencing of RTEL1 from patients predicted five out of six disease-segregating VUS to be pathogenic. We provide structural hypotheses regarding how these mutations may disrupt RTEL1 ATPase and helicase function. Spatial analysis of missense variation accurately classified candidate VUS in RTEL1 and suggests how such variants cause disease. Incorporating

Genome-wide association study identifies variants associated with autoimmune hepatitis type 1.

Science.gov (United States)

de Boer, Ynto S; van Gerven, Nicole M F; Zwiers, Antonie; Verwer, Bart J; van Hoek, Bart; van Erpecum, Karel J; Beuers, Ulrich; van Buuren, Henk R; Drenth, Joost P H; den Ouden, Jannie W; Verdonk, Robert C; Koek, Ger H; Brouwer, Johannes T; Guichelaar, Maureen M J; Vrolijk, Jan M; Kraal, Georg; Mulder, Chris J J; van Nieuwkerk, Carin M J; Fischer, Janett; Berg, Thomas; Stickel, Felix; Sarrazin, Christoph; Schramm, Christoph; Lohse, Ansgar W; Weiler-Normann, Christina; Lerch, Markus M; Nauck, Matthias; Völzke, Henry; Homuth, Georg; Bloemena, Elisabeth; Verspaget, Hein W; Kumar, Vinod; Zhernakova, Alexandra; Wijmenga, Cisca; Franke, Lude; Bouma, Gerd

2014-08-01

Autoimmune hepatitis (AIH) is an uncommon autoimmune liver disease of unknown etiology. We used a genome-wide approach to identify genetic variants that predispose individuals to AIH. We performed a genome-wide association study of 649 adults in The Netherlands with AIH type 1 and 13,436 controls. Initial associations were further analyzed in an independent replication panel comprising 451 patients with AIH type 1 in Germany and 4103 controls. We also performed an association analysis in the discovery cohort using imputed genotypes of the major histocompatibility complex region. We associated AIH with a variant in the major histocompatibility complex region at rs2187668 (P = 1.5 × 10(-78)). Analysis of this variant in the discovery cohort identified HLA-DRB1*0301 (P = 5.3 × 10(-49)) as a primary susceptibility genotype and HLA-DRB1*0401 (P = 2.8 × 10(-18)) as a secondary susceptibility genotype. We also associated AIH with variants of SH2B3 (rs3184504, 12q24; P = 7.7 × 10(-8)) and CARD10 (rs6000782, 22q13.1; P = 3.0 × 10(-6)). In addition, strong inflation of association signal was found with single-nucleotide polymorphisms associated with other immune-mediated diseases, including primary sclerosing cholangitis and primary biliary cirrhosis, but not with single-nucleotide polymorphisms associated with other genetic traits. In a genome-wide association study, we associated AIH type 1 with variants in the major histocompatibility complex region, and identified variants of SH2B3and CARD10 as likely risk factors. These findings support a complex genetic basis for AIH pathogenesis and indicate that part of the genetic susceptibility overlaps with that for other immune-mediated liver diseases. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

Oliver Sacks: Our Correspondence About Twins/Twin Research: Vanishing Twins Syndrome; Discordant Sex in MZ Twins; Pregnancy Outcomes in IVF and ICSI Conceived Twins/Print and Media: Superfetated Twins; Twins Discordant for Smoking; Twins in Fashion; Yale University Twin Hockey Players; Conjoined Twin-Visiting Professor.

Science.gov (United States)

Segal, Nancy L

2017-08-01

The late neurologist and author, Oliver Sacks, published an insightful 1986 review of Marjorie Wallace's book, The Silent Twins, in the New York Times. Taking exception to his assertion about Sir Francis Galton, I wrote a letter to the Times' editor. The letter was unpublished, but it brought a wonderful response from Sacks himself that is reproduced and examined. Next, brief reviews of twin research concerning the vanishing twin syndrome (VTS), discordant sex in a monozygotic (MZ) twin pair, and multiple pregnancy outcomes from assisted reproductive technology (ART) are presented. This section is followed by popular coverage of superfetated twins, smoking-discordant co-twins, twins in fashion, Yale University twin hockey players, and a visiting professor who was a conjoined twin.

Reared-Apart Chinese Twins: Chance Discovery/Twin-Based Research: Twin Study of Media Use; Twin Relations Over the Life Span; Breast-Feeding Opposite-Sex Twins/Print and Online Media: Twins in Fashion; Second Twin Pair Born to Tennis Star; Twin Primes; Twin Pandas.

Science.gov (United States)

Segal, Nancy L

2017-04-01

A January 2017 reunion of 10-year-old reared-apart Chinese twin girls was captured live on ABC's morning talk show Good Morning America, and rebroadcast on their evening news program Nightline. The twins' similarities and differences, and their participation in ongoing research will be described. This story is followed by reviews of twin research concerning genetic and environmental influences on media use, twin relations across the lifespan and the breast-feeding of opposite-sex twins. Popular interest items include twins in fashion, the second twin pair born to an internationally renowned tennis star, twin primes and twin pandas.

Microstructural evolution and deformation behavior of twinning-induced plasticity (TWIP) steel during wire drawing

International Nuclear Information System (INIS)

Hwang, Joong-Ki; Yi, Il-Cheol; Son, Il-Heon; Yoo, Jang-Yong; Kim, Byoungkoo; Zargaran, A.; Kim, Nack J.

2015-01-01

The effect of wire drawing on the microstructural evolution and deformation behavior of Fe–Mn–Al–C twinning-induced plasticity (TWIP) steel has been investigated. The inhomogeneities of the stress state, texture, microstructure, and mechanical properties were clarified over the cross section of drawn wire with the aid of numerical simulation, Schmid factor analysis, and electron backscatter diffraction (EBSD) techniques. The analysis of texture in drawn wire shows that a mixture of <111> and <100> fiber texture was developed with strain; however, the distribution of <111> and <100> fibers was inhomogeneous along the radial direction of wire due to uneven strain distribution and different stress state along the radial direction. It has also been shown that the morphology, volume fraction, and variant system of twins as well as twinning rate were dependent on the imposed stress state. The surface area was subjected to larger strain and more complex stress state involving compression, shear, and tension than the center area, resulting in a larger twin volume fraction and more twin variants in the former than in the latter at all the strain levels. While the surface area was saturated with twins at an early stage of drawing, the center area was not saturated with twins even at fracture, implying that the fracture of wire were initiated at the surface area because of the exhaustion of ductility due to twinning. Based on these results, it is suggested that imposing a uniform strain distribution along the radial direction of wire by the control of processing conditions such as die angle and amount of reduction per pass is necessary to increase the drawing limit of TWIP steel

Whole-Exome Sequencing Identifies Rare and Low-Frequency Coding Variants Associated with LDL Cholesterol

Science.gov (United States)

Lange, Leslie A.; Hu, Youna; Zhang, He; Xue, Chenyi; Schmidt, Ellen M.; Tang, Zheng-Zheng; Bizon, Chris; Lange, Ethan M.; Smith, Joshua D.; Turner, Emily H.; Jun, Goo; Kang, Hyun Min; Peloso, Gina; Auer, Paul; Li, Kuo-ping; Flannick, Jason; Zhang, Ji; Fuchsberger, Christian; Gaulton, Kyle; Lindgren, Cecilia; Locke, Adam; Manning, Alisa; Sim, Xueling; Rivas, Manuel A.; Holmen, Oddgeir L.; Gottesman, Omri; Lu, Yingchang; Ruderfer, Douglas; Stahl, Eli A.; Duan, Qing; Li, Yun; Durda, Peter; Jiao, Shuo; Isaacs, Aaron; Hofman, Albert; Bis, Joshua C.; Correa, Adolfo; Griswold, Michael E.; Jakobsdottir, Johanna; Smith, Albert V.; Schreiner, Pamela J.; Feitosa, Mary F.; Zhang, Qunyuan; Huffman, Jennifer E.; Crosby, Jacy; Wassel, Christina L.; Do, Ron; Franceschini, Nora; Martin, Lisa W.; Robinson, Jennifer G.; Assimes, Themistocles L.; Crosslin, David R.; Rosenthal, Elisabeth A.; Tsai, Michael; Rieder, Mark J.; Farlow, Deborah N.; Folsom, Aaron R.; Lumley, Thomas; Fox, Ervin R.; Carlson, Christopher S.; Peters, Ulrike; Jackson, Rebecca D.; van Duijn, Cornelia M.; Uitterlinden, André G.; Levy, Daniel; Rotter, Jerome I.; Taylor, Herman A.; Gudnason, Vilmundur; Siscovick, David S.; Fornage, Myriam; Borecki, Ingrid B.; Hayward, Caroline; Rudan, Igor; Chen, Y. Eugene; Bottinger, Erwin P.; Loos, Ruth J.F.; Sætrom, Pål; Hveem, Kristian; Boehnke, Michael; Groop, Leif; McCarthy, Mark; Meitinger, Thomas; Ballantyne, Christie M.; Gabriel, Stacey B.; O’Donnell, Christopher J.; Post, Wendy S.; North, Kari E.; Reiner, Alexander P.; Boerwinkle, Eric; Psaty, Bruce M.; Altshuler, David; Kathiresan, Sekar; Lin, Dan-Yu; Jarvik, Gail P.; Cupples, L. Adrienne; Kooperberg, Charles; Wilson, James G.; Nickerson, Deborah A.; Abecasis, Goncalo R.; Rich, Stephen S.; Tracy, Russell P.; Willer, Cristen J.; Gabriel, Stacey B.; Altshuler, David M.; Abecasis, Gonçalo R.; Allayee, Hooman; Cresci, Sharon; Daly, Mark J.; de Bakker, Paul I.W.; DePristo, Mark A.; Do, Ron; Donnelly, Peter; Farlow, Deborah N.; Fennell, Tim; Garimella, Kiran; Hazen, Stanley L.; Hu, Youna; Jordan, Daniel M.; Jun, Goo; Kathiresan, Sekar; Kang, Hyun Min; Kiezun, Adam; Lettre, Guillaume; Li, Bingshan; Li, Mingyao; Newton-Cheh, Christopher H.; Padmanabhan, Sandosh; Peloso, Gina; Pulit, Sara; Rader, Daniel J.; Reich, David; Reilly, Muredach P.; Rivas, Manuel A.; Schwartz, Steve; Scott, Laura; Siscovick, David S.; Spertus, John A.; Stitziel, Nathaniel O.; Stoletzki, Nina; Sunyaev, Shamil R.; Voight, Benjamin F.; Willer, Cristen J.; Rich, Stephen S.; Akylbekova, Ermeg; Atwood, Larry D.; Ballantyne, Christie M.; Barbalic, Maja; Barr, R. Graham; Benjamin, Emelia J.; Bis, Joshua; Boerwinkle, Eric; Bowden, Donald W.; Brody, Jennifer; Budoff, Matthew; Burke, Greg; Buxbaum, Sarah; Carr, Jeff; Chen, Donna T.; Chen, Ida Y.; Chen, Wei-Min; Concannon, Pat; Crosby, Jacy; Cupples, L. Adrienne; D’Agostino, Ralph; DeStefano, Anita L.; Dreisbach, Albert; Dupuis, Josée; Durda, J. Peter; Ellis, Jaclyn; Folsom, Aaron R.; Fornage, Myriam; Fox, Caroline S.; Fox, Ervin; Funari, Vincent; Ganesh, Santhi K.; Gardin, Julius; Goff, David; Gordon, Ora; Grody, Wayne; Gross, Myron; Guo, Xiuqing; Hall, Ira M.; Heard-Costa, Nancy L.; Heckbert, Susan R.; Heintz, Nicholas; Herrington, David M.; Hickson, DeMarc; Huang, Jie; Hwang, Shih-Jen; Jacobs, David R.; Jenny, Nancy S.; Johnson, Andrew D.; Johnson, Craig W.; Kawut, Steven; Kronmal, Richard; Kurz, Raluca; Lange, Ethan M.; Lange, Leslie A.; Larson, Martin G.; Lawson, Mark; Lewis, Cora E.; Levy, Daniel; Li, Dalin; Lin, Honghuang; Liu, Chunyu; Liu, Jiankang; Liu, Kiang; Liu, Xiaoming; Liu, Yongmei; Longstreth, William T.; Loria, Cay; Lumley, Thomas; Lunetta, Kathryn; Mackey, Aaron J.; Mackey, Rachel; Manichaikul, Ani; Maxwell, Taylor; McKnight, Barbara; Meigs, James B.; Morrison, Alanna C.; Musani, Solomon K.; Mychaleckyj, Josyf C.; Nettleton, Jennifer A.; North, Kari; O’Donnell, Christopher J.; O’Leary, Daniel; Ong, Frank; Palmas, Walter; Pankow, James S.; Pankratz, Nathan D.; Paul, Shom; Perez, Marco; Person, Sharina D.; Polak, Joseph; Post, Wendy S.; Psaty, Bruce M.; Quinlan, Aaron R.; Raffel, Leslie J.; Ramachandran, Vasan S.; Reiner, Alexander P.; Rice, Kenneth; Rotter, Jerome I.; Sanders, Jill P.; Schreiner, Pamela; Seshadri, Sudha; Shea, Steve; Sidney, Stephen; Silverstein, Kevin; Smith, Nicholas L.; Sotoodehnia, Nona; Srinivasan, Asoke; Taylor, Herman A.; Taylor, Kent; Thomas, Fridtjof; Tracy, Russell P.; Tsai, Michael Y.; Volcik, Kelly A.; Wassel, Chrstina L.; Watson, Karol; Wei, Gina; White, Wendy; Wiggins, Kerri L.; Wilk, Jemma B.; Williams, O. Dale; Wilson, Gregory; Wilson, James G.; Wolf, Phillip; Zakai, Neil A.; Hardy, John; Meschia, James F.; Nalls, Michael; Singleton, Andrew; Worrall, Brad; Bamshad, Michael J.; Barnes, Kathleen C.; Abdulhamid, Ibrahim; Accurso, Frank; Anbar, Ran; Beaty, Terri; Bigham, Abigail; Black, Phillip; Bleecker, Eugene; Buckingham, Kati; Cairns, Anne Marie; Caplan, Daniel; Chatfield, Barbara; Chidekel, Aaron; Cho, Michael; Christiani, David C.; Crapo, James D.; Crouch, Julia; Daley, Denise; Dang, Anthony; Dang, Hong; De Paula, Alicia; DeCelie-Germana, Joan; Drumm, Allen DozorMitch; Dyson, Maynard; Emerson, Julia; Emond, Mary J.; Ferkol, Thomas; Fink, Robert; Foster, Cassandra; Froh, Deborah; Gao, Li; Gershan, William; Gibson, Ronald L.; Godwin, Elizabeth; Gondor, Magdalen; Gutierrez, Hector; Hansel, Nadia N.; Hassoun, Paul M.; Hiatt, Peter; Hokanson, John E.; Howenstine, Michelle; Hummer, Laura K.; Kanga, Jamshed; Kim, Yoonhee; Knowles, Michael R.; Konstan, Michael; Lahiri, Thomas; Laird, Nan; Lange, Christoph; Lin, Lin; Lin, Xihong; Louie, Tin L.; Lynch, David; Make, Barry; Martin, Thomas R.; Mathai, Steve C.; Mathias, Rasika A.; McNamara, John; McNamara, Sharon; Meyers, Deborah; Millard, Susan; Mogayzel, Peter; Moss, Richard; Murray, Tanda; Nielson, Dennis; Noyes, Blakeslee; O’Neal, Wanda; Orenstein, David; O’Sullivan, Brian; Pace, Rhonda; Pare, Peter; Parker, H. Worth; Passero, Mary Ann; Perkett, Elizabeth; Prestridge, Adrienne; Rafaels, Nicholas M.; Ramsey, Bonnie; Regan, Elizabeth; Ren, Clement; Retsch-Bogart, George; Rock, Michael; Rosen, Antony; Rosenfeld, Margaret; Ruczinski, Ingo; Sanford, Andrew; Schaeffer, David; Sell, Cindy; Sheehan, Daniel; Silverman, Edwin K.; Sin, Don; Spencer, Terry; Stonebraker, Jackie; Tabor, Holly K.; Varlotta, Laurie; Vergara, Candelaria I.; Weiss, Robert; Wigley, Fred; Wise, Robert A.; Wright, Fred A.; Wurfel, Mark M.; Zanni, Robert; Zou, Fei; Nickerson, Deborah A.; Rieder, Mark J.; Green, Phil; Shendure, Jay; Akey, Joshua M.; Bustamante, Carlos D.; Crosslin, David R.; Eichler, Evan E.; Fox, P. Keolu; Fu, Wenqing; Gordon, Adam; Gravel, Simon; Jarvik, Gail P.; Johnsen, Jill M.; Kan, Mengyuan; Kenny, Eimear E.; Kidd, Jeffrey M.; Lara-Garduno, Fremiet; Leal, Suzanne M.; Liu, Dajiang J.; McGee, Sean; O’Connor, Timothy D.; Paeper, Bryan; Robertson, Peggy D.; Smith, Joshua D.; Staples, Jeffrey C.; Tennessen, Jacob A.; Turner, Emily H.; Wang, Gao; Yi, Qian; Jackson, Rebecca; Peters, Ulrike; Carlson, Christopher S.; Anderson, Garnet; Anton-Culver, Hoda; Assimes, Themistocles L.; Auer, Paul L.; Beresford, Shirley; Bizon, Chris; Black, Henry; Brunner, Robert; Brzyski, Robert; Burwen, Dale; Caan, Bette; Carty, Cara L.; Chlebowski, Rowan; Cummings, Steven; Curb, J. David; Eaton, Charles B.; Ford, Leslie; Franceschini, Nora; Fullerton, Stephanie M.; Gass, Margery; Geller, Nancy; Heiss, Gerardo; Howard, Barbara V.; Hsu, Li; Hutter, Carolyn M.; Ioannidis, John; Jiao, Shuo; Johnson, Karen C.; Kooperberg, Charles; Kuller, Lewis; LaCroix, Andrea; Lakshminarayan, Kamakshi; Lane, Dorothy; Lasser, Norman; LeBlanc, Erin; Li, Kuo-Ping; Limacher, Marian; Lin, Dan-Yu; Logsdon, Benjamin A.; Ludlam, Shari; Manson, JoAnn E.; Margolis, Karen; Martin, Lisa; McGowan, Joan; Monda, Keri L.; Kotchen, Jane Morley; Nathan, Lauren; Ockene, Judith; O’Sullivan, Mary Jo; Phillips, Lawrence S.; Prentice, Ross L.; Robbins, John; Robinson, Jennifer G.; Rossouw, Jacques E.; Sangi-Haghpeykar, Haleh; Sarto, Gloria E.; Shumaker, Sally; Simon, Michael S.; Stefanick, Marcia L.; Stein, Evan; Tang, Hua; Taylor, Kira C.; Thomson, Cynthia A.; Thornton, Timothy A.; Van Horn, Linda; Vitolins, Mara; Wactawski-Wende, Jean; Wallace, Robert; Wassertheil-Smoller, Sylvia; Zeng, Donglin; Applebaum-Bowden, Deborah; Feolo, Michael; Gan, Weiniu; Paltoo, Dina N.; Sholinsky, Phyliss; Sturcke, Anne

2014-01-01

Elevated low-density lipoprotein cholesterol (LDL-C) is a treatable, heritable risk factor for cardiovascular disease. Genome-wide association studies (GWASs) have identified 157 variants associated with lipid levels but are not well suited to assess the impact of rare and low-frequency variants. To determine whether rare or low-frequency coding variants are associated with LDL-C, we exome sequenced 2,005 individuals, including 554 individuals selected for extreme LDL-C (>98th or <2nd percentile). Follow-up analyses included sequencing of 1,302 additional individuals and genotype-based analysis of 52,221 individuals. We observed significant evidence of association between LDL-C and the burden of rare or low-frequency variants in PNPLA5, encoding a phospholipase-domain-containing protein, and both known and previously unidentified variants in PCSK9, LDLR and APOB, three known lipid-related genes. The effect sizes for the burden of rare variants for each associated gene were substantially higher than those observed for individual SNPs identified from GWASs. We replicated the PNPLA5 signal in an independent large-scale sequencing study of 2,084 individuals. In conclusion, this large whole-exome-sequencing study for LDL-C identified a gene not known to be implicated in LDL-C and provides unique insight into the design and analysis of similar experiments. PMID:24507775

The 16th International Twin Congress: Highlights from Madrid/Twin Research: Twin Study of Partner Aggression; ABO Incompatibility in Dizygotic Twins; Growth Discordance in a Monoamniotic Twin Pair; Quick Note on Twin Implantation/In the Media: Long-Lost Twins Found; NASA Twin Experiment; Twin Brothers and the Las Vegas Attack; Retired Twin Airline Pilots; Twin Film Clips.

Science.gov (United States)

Segal, Nancy L

2018-02-01

Highlights from the 16th International Twin Congress, held in Madrid, Spain from November 16-18, 2017, are presented. The Twin Congress, formerly held every three years, now takes place biennially with a single-day meeting organized during the off years. This meeting is the largest gathering of scientific twin researchers, medical personnel, and representatives of multiple birth organizations in the world. This overview is followed by reviews of recent twin research and commentary concerning partner aggression, ABO incompatibility in dizygotic twins, growth discordance in a monoamniotic twin pair and twin implantation. The article closes with summaries of timely topics in the media, namely a father's finding of his long-lost twin children, early results from the NASA twin experiment, twin brothers at the center of the October 2017 Las Vegas attack, retired twin airline pilots, and clips from recent films with twin-based themes.

Exome genotyping arrays to identify rare and low frequency variants associated with epithelial ovarian cancer risk

DEFF Research Database (Denmark)

Permuth, Jennifer B; Pirie, Ailith; Ann Chen, Y

2016-01-01

Rare and low frequency variants are not well covered in most germline genotyping arrays and are understudied in relation to epithelial ovarian cancer (EOC) risk. To address this gap, we used genotyping arrays targeting rarer protein-coding variation in 8,165 EOC cases and 11,619 controls from...... that is in LD (r(2 )=( )0.90) with a previously identified 'best hit' (rs7651446) mapping to an intron of TIPARP. Suggestive associations (5.0 × 10 (-)  (5 )>( )P≥5.0 ×10 (-)  (7)) were detected for rare and low-frequency variants at 16 novel loci. Four rare missense variants were identified (ACTBL2 rs73757391.......67 × 10 (-)  (4); PSKAT-o = 1.07 × 10 (-)  (5)), reaffirming variant-level analysis. In summary, this large study identified several rare and low-frequency variants and genes that may contribute to EOC susceptibility, albeit with possible small effects. Future studies that integrate epidemiology...

The Brazilian Twin Registry.

Science.gov (United States)

Ferreira, Paulo H; Oliveira, Vinicius C; Junqueira, Daniela R; Cisneros, Lígia C; Ferreira, Lucas C; Murphy, Kate; Ordoñana, Juan R; Hopper, John L; Teixeira-Salmela, Luci F

2016-12-01

The Brazilian Twin Registry (BTR) was established in 2013 and has impelled twin research in South America. The main aim of the initiative was to create a resource that would be accessible to the Brazilian scientific community as well as international researchers interested in the investigation of the contribution of genetic and environmental factors in the development of common diseases, phenotypes, and human behavior traits. The BTR is a joint effort between academic and governmental institutions from Brazil and Australia. The collaboration includes the Federal University of Minas Gerais (UFMG) in Brazil, the University of Sydney and University of Melbourne in Australia, the Australian Twin Registry, as well as the research foundations CNPq and CAPES in Brazil. The BTR is a member of the International Network of Twin Registries. Recruitment strategies used to register twins have been through participation in a longitudinal study investigating genetic and environmental factors for low back pain occurrence, and from a variety of sources including media campaigns and social networking. Currently, 291 twins are registered in the BTR, with data on demographics, zygosity, anthropometrics, and health history having been collected from 151 twins using a standardized self-reported questionnaire. Future BTR plans include the registration of thousands of Brazilian twins identified from different sources and collaborate nationally and internationally with other research groups interested on twin studies.

Evaluation of common genetic variants identified by GWAS for early onset and morbid obesity in population-based samples

DEFF Research Database (Denmark)

den Hoed, M; Luan, J; Langenberg, C

2013-01-01

BACKGROUND: Meta-analysis of case-control genome-wide association studies (GWAS) for early onset and morbid obesity identified four variants in/near the PRL, PTER, MAF and NPC1 genes. OBJECTIVE: We aimed to validate association of these variants with obesity-related traits in population-based sam......BACKGROUND: Meta-analysis of case-control genome-wide association studies (GWAS) for early onset and morbid obesity identified four variants in/near the PRL, PTER, MAF and NPC1 genes. OBJECTIVE: We aimed to validate association of these variants with obesity-related traits in population......, these variants, which were identified in a GWAS for early onset and morbid obesity, do not seem to influence obesity-related traits in the general population....

Heritability and Genome-Wide Association Analyses of Serum Uric Acid in Middle and Old-Aged Chinese Twins

Directory of Open Access Journals (Sweden)

Weijing Wang

2018-03-01

Full Text Available Serum uric acid (SUA, as the end product of purine metabolism, has proven emerging roles in human disorders. Here based on a sample of 379 middle and old-aged Chinese twin pairs, we aimed to explore the magnitude of genetic impact on SUA variation by performing sex-limitation twin modeling analyses and further detect specific genetic variants related to SUA by conducting a genome-wide association study. Monozygotic (MZ twin correlation for SUA level (rMZ = 0.56 was larger than for dizygotic (DZ twin correlation (rDZ = 0.39. The common effects sex-limitation model provided the best fit with additive genetic parameter (A accounting for 46.3%, common or shared environmental parameter (C accounting for 26.3% and unique/nonshared environmental parameter (E accounting for 27.5% for females and 29.9, 33.1, and 37.0% for males, respectively. Although no SUA-related genetic variants reached genome-wide significance level, 25 SNPs were suggestive of association (P < 1 × 10−5. Most of the SNPs were located in an intronic region and detected to have regulatory effects on gene transcription. The cell-type specific enhancer of skeletal muscle was detected which has been reported to implicate SUA. Two promising genetic regions on chromosome 17 around rs2253277 and chromosome 14 around rs11621523 were found. Gene-based analysis found 167 genes nominally associated with SUA level (P < 0.05, including PTGR2, ENTPD5, well-known SLC2A9, etc. Enrichment analysis identified one pathway of transmembrane transport of small molecules and 20 GO gene sets involving in ion transport, transmembrane transporter activity, hydrolase activity acting on acid anhydrides, etc. In conclusion, SUA shows moderate heritability in women and low heritability in men in the Chinese population and genetic variations are significantly involved in functional genes and regulatory domains that mediate SUA level. Our findings provide clues to further elucidate molecular

Exome Sequencing Identifies Potential Risk Variants for Mendelian Disorders at High Prevalence in Qatar

Science.gov (United States)

Rodriguez-Flores, Juan L.; Fakhro, Khalid; Hackett, Neil R.; Salit, Jacqueline; Fuller, Jennifer; Agosto-Perez, Francisco; Gharbiah, Maey; Malek, Joel A.; Zirie, Mahmoud; Jayyousi, Amin; Badii, Ramin; Al-Marri, Ajayeb Al-Nabet; Chouchane, Lotfi; Stadler, Dora J.; Hunter-Zinck, Haley; Mezey, Jason G.; Crystal, Ronald G.

2013-01-01

Exome sequencing of families of related individuals has been highly successful in identifying genetic polymorphisms responsible for Mendelian disorders. Here, we demonstrate the value of the reverse approach, where we use exome sequencing of a sample of unrelated individuals to analyze allele frequencies of known causal mutations for Mendelian diseases. We sequenced the exomes of 100 individuals representing the three major genetic subgroups of the Qatari population (Q1 Bedouin, Q2 Persian-South Asian, Q3 African) and identified 37 variants in 33 genes with effects on 36 clinically significant Mendelian diseases. These include variants not present in 1000 Genomes and variants at high frequency when compared to 1000 Genomes populations. Several of these Mendelian variants were only segregating in one Qatari subpopulation, where the observed subpopulation specificity trends were confirmed in an independent population of 386 Qataris. Pre-marital genetic screening in Qatar tests for only 4 out of the 37, such that this study provides a set of Mendelian disease variants with potential impact on the epidemiological profile of the population that could be incorporated into the testing program if further experimental and clinical characterization confirms high penetrance. PMID:24123366

Variance components models for physical activity with age as modifier: a comparative twin study in seven countries

DEFF Research Database (Denmark)

Vink, Jacqueline M; Boomsma, Dorret I; Medland, Sarah E

2011-01-01

-reported data from twins aged 19 to 50 from seven countries that collaborated in the GenomEUtwin project: Australia, Denmark, Finland, Norway, Netherlands, Sweden and United Kingdom. Results confirmed the importance of genetic influences on physical activity in all countries and showed an age-related decrease......Physical activity is influenced by genetic factors whose expression may change with age. We employed an extension to the classical twin model that allows a modifier variable, age, to interact with the effects of the latent genetic and environmental factors. The model was applied to self...... into account when exploring the genetic and environmental contribution to physical activity. It also suggests that the power of genome-wide association studies to identify the genetic variants contributing to physical activity may be larger in young adult cohorts....

Twin-twin transfusion syndrome - diagnosis and prognosis

Directory of Open Access Journals (Sweden)

Hajrić-Egić Amira

2003-01-01

Full Text Available Twin-twin transfusion syndrome is a serious complication of monozygotic, monochorionic, diamniotic twins resulting from transplacental vascular communications. In this syndrome blood is thought to be shunted from one twin - donor,who develops anaemia,growth retardation and oligoamnios, to the other twin - recipient,who becomes plethoric,macrosomic and develops polyhydroamnios. The incidence of twin-twin transfusion syndrome ranges from 5-15% of all twin pregnancies. If this condition develops in the second trimester, it is usually associated with spontaneous abortion and death of one or both fetuses before viability. Developing the syndrome in the third trimester has better perinatal outcome. Mortality rates ranging from 56%-100%, depending on gestational age and severity of the syndrome. The ultrasound criterias for diagnosis, in this study,were the presence of twins of the same sex with discordant growth, with oligohydroamnios in one twin sac and polyhydroamnios in the other one, one placenta and thin membrane between twins. The present study shows clinical course of 14 cases and value of Doppler ultrasound to analyze the usefulness of umbilical artery blood flow velocimetry for predicting the risk of twin-twin transfusion syndrome. 14 twin pregnancies with twin-twin transfusion syndrome were diagnosed during the last four years period and prospectivelly followed. 9 cases were diagnosed before the completion od 28 weeks of gestation.The mean gestational age was 21,6_+4,2 weeks at diagnosis and 23,2+_3,6 weeks at delivery. 5 cases were diagnosed after 28 weeks of gestation. The mean gestational age in this group was 29,6+_2,1 weeks at diagnosis and 33+_3,3 weeks at delivery. The survival rate in this study was 29%(8/28.9 cases ended in spontaneous abortion between 18th and 27th weeks of pregnancy (table 1 and 5 in premature labor (table 2.There were 7 intrauterine death (5 at admission and 2 few days after admission and 13 neonatal deaths

The USC Adult Twin Cohorts: International Twin Study and California Twin Program.

Science.gov (United States)

Cozen, Wendy; Hwang, Amie E; Cockburn, Myles G; Hamilton, Ann S; Zadnick, John; Mack, Thomas M

2013-02-01

The study of twin subjects permits the documentation of crude heritability and may promote the identification of specific causal alleles. We believe that at the current time, the chief research advantage of twins as subjects, especially monozygotic twins, is that the commonality of their genetic and cultural identity simplifies the interpretation of biological associations. In order to study genetic and environmental determinants of cancer and chronic diseases, we developed two twin registries, maintained at the University of Southern California: The International Twin Study (ITS) and the California Twin Program (CTP). The ITS is a volunteer registry of twins with cancer and chronic disease consisting of 17,245 twin pairs affected by cancer and chronic disease, respectively, ascertained by advertising in periodicals from 1980-1991. The CTP is a population-based registry of California-born twin pairs ascertained by linking the California birth records to the State Department of Motor Vehicles. Over 51,000 individual California twins representing 36,965 pairs completed and returned 16-page questionnaires. Cancer diagnoses in the California twins are updated by regular linkage to the California Cancer Registry. Over 5,000 cancer patients are represented in the CTP. Twins from both registries have participated extensively in studies of breast cancer, melanoma, lymphoma, multiple sclerosis, systemic lupus erythematosus, diabetes mellitus type 1, mammographic density, smoking, and other traits and conditions.

Perinatal hepatic infarction in twin-twin transfusion.

LENUS (Irish Health Repository)

O'Sullivan, M J

2012-02-03

We report a case of a twin pregnancy which was complicated by a twin-twin transfusion in which the recipient twin was noted to have an intra-abdominal echogenic mass. This twin died at two days of age of hepatic infarction. The donor twin was healthy at birth, at thirty weeks\\' gestation, and did not have any subsequent problems. Fetal intra-abdominal echogenicity may be a marker of hepatic infarction.

Reversible twin boundary migration between α″ martensites in a Ti-Nb-Zr-Sn alloy

Energy Technology Data Exchange (ETDEWEB)

Yao, Tingting; Du, Kui, E-mail: kuidu@imr.ac.cn; Wang, Haoliang; Qi, Lu; He, Suyun; Hao, Yulin; Yang, Rui; Ye, Hengqiang

2017-03-14

Cyclic tensile loading tests and transmission electron microscopy investigation are conducted on a Ti-24Nb-4Zr-8Sn (wt%) alloy. Under tensile strain less than 3.3%, most of the deformation strain recovers after unloading but significant energy dissipation occurs during the loading-unloading cycle. Reversible migration of twin boundaries between α″ martensite variants, in virtue of dislocation movement on the twin boundaries, has been revealed by time resolved high-resolution transmission electron microscopy. This twin boundary migration contributes to the energy dissipation effect and consequently the damping property of the titanium alloy.

Using Extreme Phenotype Sampling to Identify the Rare Causal Variants of Quantitative Traits in Association Studies

OpenAIRE

Li, Dalin; Lewinger, Juan Pablo; Gauderman, William J.; Murcray, Cassandra Elizabeth; Conti, David

2011-01-01

Variants identified in recent genome-wide association studies based on the common-disease common-variant hypothesis are far from fully explaining the hereditability of complex traits. Rare variants may, in part, explain some of the missing hereditability. Here, we explored the advantage of the extreme phenotype sampling in rare-variant analysis and refined this design framework for future large-scale association studies on quantitative traits. We first proposed a power calculation approach fo...

Exome Genotyping Identifies Pleiotropic Variants Associated with Red Blood Cell Traits

NARCIS (Netherlands)

Chami, N. (Nathalie); M.-H. Chen (Ming-Huei); Slater, A.J. (Andrew J.); Eicher, J.D. (John D.); E. Evangelou (Evangelos); Tajuddin, S.M. (Salman M.); Love-Gregory, L. (Latisha); T. Kacprowski (Tim); U.M. Schick (Ursula); Nomura, A. (Akihiro); Giri, A. (Ayush); Lessard, S. (Samuel); J. Brody (Jennifer); C. Schurmann (Claudia); V.S. Pankratz (Shane); L.R. Yanek (Lisa); A. Manichaikul (Ani); R. Pazoki (Raha); E. Mihailov (Evelin); W.D. Hill (W. David); Raffield, L.M. (Laura M.); A.D. Burt (Alastair); T.M. Bartz (Traci M.); D.M. Becker (Diane); L.C. Becker (Lewis); E.A. Boerwinkle (Eric); J. Bork-Jensen (Jette); E.P. Bottinger (Erwin); M.L. O'Donoghue (Michelle L.); D.R. Crosslin (David); de Denus, S. (Simon); Dubé, M.-P. (Marie-Pierre); P. Elliott (Paul); G. Engström; M. Evans (Michele); J. Floyd (James); M. Fornage (Myriam); Gao, H. (He); A. Greinacher (Andreas); V. Gudnason (Vilmundur); T. Hansen (T.); T.B. Harris (Tamara); C. Hayward (Caroline); Hernesniemi, J. (Jussi); H. Highland (Heather); J.N. Hirschhorn (Joel); Hofman, A. (Albert); Irvin, M.R. (Marguerite R.); M. Kähönen (Mika); E.M. Lange (Ethan); Launer, L.J. (Lenore J.); T. Lehtimäki (Terho); Li, J. (Jin); D.C. Liewald (David C.); A. Linneberg (Allan); Y. Liu (YongMei); Y. Lu (Yingchang); L.-P. Lyytikäinen (Leo-Pekka); R. Mägi (Reedik); J. Mathias (Jasmine); O. Melander (Olle); A. Metspalu (Andres); K. Mononen (Kari); M.A. Nalls (Michael); D.A. Nickerson (Deborah); K. Nikus (Kjell); C.J. O'Donnell (Christopher); M. Orho-Melander (Marju); O. Pedersen (Oluf); A. Petersmann (Astrid); Polfus, L. (Linda); B.M. Psaty (Bruce); O.T. Raitakari (Olli T.); Raitoharju, E. (Emma); Richard, M. (Melissa); K.M. Rice (Kenneth); F. Rivadeneira Ramirez (Fernando); Rotter, J.I. (Jerome I.); Schmidt, F. (Frank); A.V. Smith (Albert Vernon); J.M. Starr (John); K.D. Taylor (Kent); A. Teumer (Alexander); Thuesen, B.H. (Betina H.); Torstenson, E.S. (Eric S.); R.P. Tracy (Russell); I. Tzoulaki; N.A. Zakai (Neil); Vacchi-Suzzi, C. (Caterina); C.M. van Duijn (Cornelia); F.J.A. van Rooij (Frank); M. Cushman (Mary Ann); I.J. Deary (Ian J.); Velez Edwards, D.R. (Digna R.); Vergnaud, A.-C. (Anne-Claire); L.C. Wallentin (Lars); D. Waterworth (Dawn); White, H.D. (Harvey D.); J.F. Wilson (James); A.B. Zonderman; S. Kathiresan (Sekar); N. Grarup (Niels); T. Esko (Tõnu); R.J.F. Loos (Ruth); L.A. Lange (Leslie); Faraday, N. (Nauder); Abumrad, N.A. (Nada A.); T.L. Edwards (Todd L.); S.K. Ganesh (Santhi); P. Auer (Paul); A.D. Johnson (Andrew); A. Reiner (Alexander); G. Lettre (Guillaume)

2016-01-01

textabstractRed blood cell (RBC) traits are important heritable clinical biomarkers and modifiers of disease severity. To identify coding genetic variants associated with these traits, we conducted meta-analyses of seven RBC phenotypes in 130,273 multi-ethnic individuals from studies genotyped on an

Genome-wide scan of healthy human connectome discovers SPON1 gene variant influencing dementia severity

Science.gov (United States)

Jahanshad, Neda; Rajagopalan, Priya; Hua, Xue; Hibar, Derrek P.; Nir, Talia M.; Toga, Arthur W.; Jack, Clifford R.; Saykin, Andrew J.; Green, Robert C.; Weiner, Michael W.; Medland, Sarah E.; Montgomery, Grant W.; Hansell, Narelle K.; McMahon, Katie L.; de Zubicaray, Greig I.; Martin, Nicholas G.; Wright, Margaret J.; Thompson, Paul M.; Weiner, Michael; Aisen, Paul; Weiner, Michael; Aisen, Paul; Petersen, Ronald; Jack, Clifford R.; Jagust, William; Trojanowski, John Q.; Toga, Arthur W.; Beckett, Laurel; Green, Robert C.; Saykin, Andrew J.; Morris, John; Liu, Enchi; Green, Robert C.; Montine, Tom; Petersen, Ronald; Aisen, Paul; Gamst, Anthony; Thomas, Ronald G.; Donohue, Michael; Walter, Sarah; Gessert, Devon; Sather, Tamie; Beckett, Laurel; Harvey, Danielle; Gamst, Anthony; Donohue, Michael; Kornak, John; Jack, Clifford R.; Dale, Anders; Bernstein, Matthew; Felmlee, Joel; Fox, Nick; Thompson, Paul; Schuff, Norbert; Alexander, Gene; DeCarli, Charles; Jagust, William; Bandy, Dan; Koeppe, Robert A.; Foster, Norm; Reiman, Eric M.; Chen, Kewei; Mathis, Chet; Morris, John; Cairns, Nigel J.; Taylor-Reinwald, Lisa; Trojanowki, J.Q.; Shaw, Les; Lee, Virginia M.Y.; Korecka, Magdalena; Toga, Arthur W.; Crawford, Karen; Neu, Scott; Saykin, Andrew J.; Foroud, Tatiana M.; Potkin, Steven; Shen, Li; Khachaturian, Zaven; Frank, Richard; Snyder, Peter J.; Molchan, Susan; Kaye, Jeffrey; Quinn, Joseph; Lind, Betty; Dolen, Sara; Schneider, Lon S.; Pawluczyk, Sonia; Spann, Bryan M.; Brewer, James; Vanderswag, Helen; Heidebrink, Judith L.; Lord, Joanne L.; Petersen, Ronald; Johnson, Kris; Doody, Rachelle S.; Villanueva-Meyer, Javier; Chowdhury, Munir; Stern, Yaakov; Honig, Lawrence S.; Bell, Karen L.; Morris, John C.; Ances, Beau; Carroll, Maria; Leon, Sue; Mintun, Mark A.; Schneider, Stacy; Marson, Daniel; Griffith, Randall; Clark, David; Grossman, Hillel; Mitsis, Effie; Romirowsky, Aliza; deToledo-Morrell, Leyla; Shah, Raj C.; Duara, Ranjan; Varon, Daniel; Roberts, Peggy; Albert, Marilyn; Onyike, Chiadi; Kielb, Stephanie; Rusinek, Henry; de Leon, Mony J.; Glodzik, Lidia; De Santi, Susan; Doraiswamy, P. Murali; Petrella, Jeffrey R.; Coleman, R. Edward; Arnold, Steven E.; Karlawish, Jason H.; Wolk, David; Smith, Charles D.; Jicha, Greg; Hardy, Peter; Lopez, Oscar L.; Oakley, MaryAnn; Simpson, Donna M.; Porsteinsson, Anton P.; Goldstein, Bonnie S.; Martin, Kim; Makino, Kelly M.; Ismail, M. Saleem; Brand, Connie; Mulnard, Ruth A.; Thai, Gaby; Mc-Adams-Ortiz, Catherine; Womack, Kyle; Mathews, Dana; Quiceno, Mary; Diaz-Arrastia, Ramon; King, Richard; Weiner, Myron; Martin-Cook, Kristen; DeVous, Michael; Levey, Allan I.; Lah, James J.; Cellar, Janet S.; Burns, Jeffrey M.; Anderson, Heather S.; Swerdlow, Russell H.; Apostolova, Liana; Lu, Po H.; Bartzokis, George; Silverman, Daniel H.S.; Graff-Radford, Neill R.; Parfitt, Francine; Johnson, Heather; Farlow, Martin R.; Hake, Ann Marie; Matthews, Brandy R.; Herring, Scott; van Dyck, Christopher H.; Carson, Richard E.; MacAvoy, Martha G.; Chertkow, Howard; Bergman, Howard; Hosein, Chris; Black, Sandra; Stefanovic, Bojana; Caldwell, Curtis; Hsiung, Ging-Yuek Robin; Feldman, Howard; Mudge, Benita; Assaly, Michele; Kertesz, Andrew; Rogers, John; Trost, Dick; Bernick, Charles; Munic, Donna; Kerwin, Diana; Mesulam, Marek-Marsel; Lipowski, Kristina; Wu, Chuang-Kuo; Johnson, Nancy; Sadowsky, Carl; Martinez, Walter; Villena, Teresa; Turner, Raymond Scott; Johnson, Kathleen; Reynolds, Brigid; Sperling, Reisa A.; Johnson, Keith A.; Marshall, Gad; Frey, Meghan; Yesavage, Jerome; Taylor, Joy L.; Lane, Barton; Rosen, Allyson; Tinklenberg, Jared; Sabbagh, Marwan; Belden, Christine; Jacobson, Sandra; Kowall, Neil; Killiany, Ronald; Budson, Andrew E.; Norbash, Alexander; Johnson, Patricia Lynn; Obisesan, Thomas O.; Wolday, Saba; Bwayo, Salome K.; Lerner, Alan; Hudson, Leon; Ogrocki, Paula; Fletcher, Evan; Carmichael, Owen; Olichney, John; DeCarli, Charles; Kittur, Smita; Borrie, Michael; Lee, T.-Y.; Bartha, Rob; Johnson, Sterling; Asthana, Sanjay; Carlsson, Cynthia M.; Potkin, Steven G.; Preda, Adrian; Nguyen, Dana; Tariot, Pierre; Fleisher, Adam; Reeder, Stephanie; Bates, Vernice; Capote, Horacio; Rainka, Michelle; Scharre, Douglas W.; Kataki, Maria; Zimmerman, Earl A.; Celmins, Dzintra; Brown, Alice D.; Pearlson, Godfrey D.; Blank, Karen; Anderson, Karen; Saykin, Andrew J.; Santulli, Robert B.; Schwartz, Eben S.; Sink, Kaycee M.; Williamson, Jeff D.; Garg, Pradeep; Watkins, Franklin; Ott, Brian R.; Querfurth, Henry; Tremont, Geoffrey; Salloway, Stephen; Malloy, Paul; Correia, Stephen; Rosen, Howard J.; Miller, Bruce L.; Mintzer, Jacobo; Longmire, Crystal Flynn; Spicer, Kenneth; Finger, Elizabeth; Rachinsky, Irina; Rogers, John; Kertesz, Andrew; Drost, Dick

2013-01-01

Aberrant connectivity is implicated in many neurological and psychiatric disorders, including Alzheimer’s disease and schizophrenia. However, other than a few disease-associated candidate genes, we know little about the degree to which genetics play a role in the brain networks; we know even less about specific genes that influence brain connections. Twin and family-based studies can generate estimates of overall genetic influences on a trait, but genome-wide association scans (GWASs) can screen the genome for specific variants influencing the brain or risk for disease. To identify the heritability of various brain connections, we scanned healthy young adult twins with high-field, high-angular resolution diffusion MRI. We adapted GWASs to screen the brain’s connectivity pattern, allowing us to discover genetic variants that affect the human brain’s wiring. The association of connectivity with the SPON1 variant at rs2618516 on chromosome 11 (11p15.2) reached connectome-wide, genome-wide significance after stringent statistical corrections were enforced, and it was replicated in an independent subsample. rs2618516 was shown to affect brain structure in an elderly population with varying degrees of dementia. Older people who carried the connectivity variant had significantly milder clinical dementia scores and lower risk of Alzheimer’s disease. As a posthoc analysis, we conducted GWASs on several organizational and topological network measures derived from the matrices to discover variants in and around genes associated with autism (MACROD2), development (NEDD4), and mental retardation (UBE2A) significantly associated with connectivity. Connectome-wide, genome-wide screening offers substantial promise to discover genes affecting brain connectivity and risk for brain diseases. PMID:23471985

Targeted deep resequencing identifies coding variants in the PEAR1 gene that play a role in platelet aggregation.

Directory of Open Access Journals (Sweden)

Yoonhee Kim

Full Text Available Platelet aggregation is heritable, and genome-wide association studies have detected strong associations with a common intronic variant of the platelet endothelial aggregation receptor1 (PEAR1 gene both in African American and European American individuals. In this study, we used a sequencing approach to identify additional exonic variants in PEAR1 that may also determine variability in platelet aggregation in the GeneSTAR Study. A 0.3 Mb targeted region on chromosome 1q23.1 including the entire PEAR1 gene was Sanger sequenced in 104 subjects (45% male, 49% African American, age = 52±13 selected on the basis of hyper- and hypo- aggregation across three different agonists (collagen, epinephrine, and adenosine diphosphate. Single-variant and multi-variant burden tests for association were performed. Of the 235 variants identified through sequencing, 61 were novel, and three of these were missense variants. More rare variants (MAF<5% were noted in African Americans compared to European Americans (108 vs. 45. The common intronic GWAS-identified variant (rs12041331 demonstrated the most significant association signal in African Americans (p = 4.020×10(-4; no association was seen for additional exonic variants in this group. In contrast, multi-variant burden tests indicated that exonic variants play a more significant role in European Americans (p = 0.0099 for the collective coding variants compared to p = 0.0565 for intronic variant rs12041331. Imputation of the individual exonic variants in the rest of the GeneSTAR European American cohort (N = 1,965 supports the results noted in the sequenced discovery sample: p = 3.56×10(-4, 2.27×10(-7, 5.20×10(-5 for coding synonymous variant rs56260937 and collagen, epinephrine and adenosine diphosphate induced platelet aggregation, respectively. Sequencing approaches confirm that a common intronic variant has the strongest association with platelet aggregation in African Americans

Postpartum Mental State of Mothers of Twins

Science.gov (United States)

Brantmüller, Éva; Gyúró, Mónika; Galgán, Kitti; Pakai, Annamária

2016-01-01

Twin birth is a relevant risk factor for postnatal depression (PND). The primary objective of our study is to reveal the prevalence of suspected cases of depression and to identify some background factors among mothers of twins. We applied convenience sampling method within a retrospective, quantitative study among mothers given birth to twins for…

An Efficient Stepwise Statistical Test to Identify Multiple Linked Human Genetic Variants Associated with Specific Phenotypic Traits.

Directory of Open Access Journals (Sweden)

Iksoo Huh

Full Text Available Recent advances in genotyping methodologies have allowed genome-wide association studies (GWAS to accurately identify genetic variants that associate with common or pathological complex traits. Although most GWAS have focused on associations with single genetic variants, joint identification of multiple genetic variants, and how they interact, is essential for understanding the genetic architecture of complex phenotypic traits. Here, we propose an efficient stepwise method based on the Cochran-Mantel-Haenszel test (for stratified categorical data to identify causal joint multiple genetic variants in GWAS. This method combines the CMH statistic with a stepwise procedure to detect multiple genetic variants associated with specific categorical traits, using a series of associated I × J contingency tables and a null hypothesis of no phenotype association. Through a new stratification scheme based on the sum of minor allele count criteria, we make the method more feasible for GWAS data having sample sizes of several thousands. We also examine the properties of the proposed stepwise method via simulation studies, and show that the stepwise CMH test performs better than other existing methods (e.g., logistic regression and detection of associations by Markov blanket for identifying multiple genetic variants. Finally, we apply the proposed approach to two genomic sequencing datasets to detect linked genetic variants associated with bipolar disorder and obesity, respectively.

Pregnancy outcome of monochorionic twins: does amnionicity matter?

Science.gov (United States)

Dias, Thiran; Contro, Elena; Thilaganathan, Basky; Khan, Hina; Zanardini, Cristina; Mahsud-Dornan, Samina; Bhide, Amar

2011-12-01

To compare the fetal loss rate of monochorionic (MC) twin pregnancies according to their amnionicity. A retrospective review of all MC pregnancy outcomes in a tertiary centre. Pregnancy outcomes were compared for monochorionic monoamniotic (MCMA) versus monochorionic diamniotic (MCDA) pregnancies. 29 MCMA and 117 MCDA twin pregnancies were identified. The overall fetal loss rate was significantly higher in MCMA (23/52, 44.2%) compared to MCDA pregnancies (28/233, 12%, Chi squared = 30.03, p fetal survival rate in MCDA twins were significantly higher than in MCMA twins (Log-rank Chi-squared = 27.9, p fetal losses in some MCMA twins. After exclusion of identifiable causes, the difference in fetal survival was not significant in the two groups (Log-rank chi-squared = 0.373, p = .54). The loss rate for MCMA twins is high and occurs mainly due to discordant congenital abnormality, conjoint twins or twin reversed arterial perfusion (TRAP) sequence. Although the fetal loss rate in MCDA is lower than in MCMA pregnancies, the majority of fetal loss in MCDA pregnancies cannot be predicted at the first scan at presentation. The data of this study questions the widespread policy of a difference in the scheduling of elective delivery for MCMA and MCDA twins.

Genome-wide association study with 1000 genomes imputation identifies signals for nine sex hormone-related phenotypes.

Science.gov (United States)

Ruth, Katherine S; Campbell, Purdey J; Chew, Shelby; Lim, Ee Mun; Hadlow, Narelle; Stuckey, Bronwyn G A; Brown, Suzanne J; Feenstra, Bjarke; Joseph, John; Surdulescu, Gabriela L; Zheng, Hou Feng; Richards, J Brent; Murray, Anna; Spector, Tim D; Wilson, Scott G; Perry, John R B

2016-02-01

Genetic factors contribute strongly to sex hormone levels, yet knowledge of the regulatory mechanisms remains incomplete. Genome-wide association studies (GWAS) have identified only a small number of loci associated with sex hormone levels, with several reproductive hormones yet to be assessed. The aim of the study was to identify novel genetic variants contributing to the regulation of sex hormones. We performed GWAS using genotypes imputed from the 1000 Genomes reference panel. The study used genotype and phenotype data from a UK twin register. We included 2913 individuals (up to 294 males) from the Twins UK study, excluding individuals receiving hormone treatment. Phenotypes were standardised for age, sex, BMI, stage of menstrual cycle and menopausal status. We tested 7,879,351 autosomal SNPs for association with levels of dehydroepiandrosterone sulphate (DHEAS), oestradiol, free androgen index (FAI), follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin, progesterone, sex hormone-binding globulin and testosterone. Eight independent genetic variants reached genome-wide significance (P<5 × 10(-8)), with minor allele frequencies of 1.3-23.9%. Novel signals included variants for progesterone (P=7.68 × 10(-12)), oestradiol (P=1.63 × 10(-8)) and FAI (P=1.50 × 10(-8)). A genetic variant near the FSHB gene was identified which influenced both FSH (P=1.74 × 10(-8)) and LH (P=3.94 × 10(-9)) levels. A separate locus on chromosome 7 was associated with both DHEAS (P=1.82 × 10(-14)) and progesterone (P=6.09 × 10(-14)). This study highlights loci that are relevant to reproductive function and suggests overlap in the genetic basis of hormone regulation.

Whole-Exome Sequencing Identifies One De Novo Variant in the FGD6 Gene in a Thai Family with Autism Spectrum Disorder

Directory of Open Access Journals (Sweden)

Chuphong Thongnak

2018-01-01

Full Text Available Autism spectrum disorder (ASD has a strong genetic basis, although the genetics of autism is complex and it is unclear. Genetic testing such as microarray or sequencing was widely used to identify autism markers, but they are unsuccessful in several cases. The objective of this study is to identify causative variants of autism in two Thai families by using whole-exome sequencing technique. Whole-exome sequencing was performed with autism-affected children from two unrelated families. Each sample was sequenced on SOLiD 5500xl Genetic Analyzer system followed by combined bioinformatics pipeline including annotation and filtering process to identify candidate variants. Candidate variants were validated, and the segregation study with other family members was performed using Sanger sequencing. This study identified a possible causative variant for ASD, c.2951G>A, in the FGD6 gene. We demonstrated the potential for ASD genetic variants associated with ASD using whole-exome sequencing and a bioinformatics filtering procedure. These techniques could be useful in identifying possible causative ASD variants, especially in cases in which variants cannot be identified by other techniques.

Exome genotyping arrays to identify rare and low frequency variants associated with epithelial ovarian cancer risk

Science.gov (United States)

Permuth, Jennifer B.; Pirie, Ailith; Ann Chen, Y.; Lin, Hui-Yi; Reid, Brett M.; Chen, Zhihua; Monteiro, Alvaro; Dennis, Joe; Mendoza-Fandino, Gustavo; Anton-Culver, Hoda; Bandera, Elisa V.; Bisogna, Maria; Brinton, Louise; Brooks-Wilson, Angela; Carney, Michael E.; Chenevix-Trench, Georgia; Cook, Linda S.; Cramer, Daniel W.; Cunningham, Julie M.; Cybulski, Cezary; D’Aloisio, Aimee A.; Anne Doherty, Jennifer; Earp, Madalene; Edwards, Robert P.; Fridley, Brooke L.; Gayther, Simon A.; Gentry-Maharaj, Aleksandra; Goodman, Marc T.; Gronwald, Jacek; Hogdall, Estrid; Iversen, Edwin S.; Jakubowska, Anna; Jensen, Allan; Karlan, Beth Y.; Kelemen, Linda E.; Kjaer, Suzanne K.; Kraft, Peter; Le, Nhu D.; Levine, Douglas A.; Lissowska, Jolanta; Lubinski, Jan; Matsuo, Keitaro; Menon, Usha; Modugno, Rosemary; Moysich, Kirsten B.; Nakanishi, Toru; Ness, Roberta B.; Olson, Sara; Orlow, Irene; Pearce, Celeste L.; Pejovic, Tanja; Poole, Elizabeth M.; Ramus, Susan J.; Anne Rossing, Mary; Sandler, Dale P.; Shu, Xiao-Ou; Song, Honglin; Taylor, Jack A.; Teo, Soo-Hwang; Terry, Kathryn L.; Thompson, Pamela J.; Tworoger, Shelley S.; Webb, Penelope M.; Wentzensen, Nicolas; Wilkens, Lynne R.; Winham, Stacey; Woo, Yin-Ling; Wu, Anna H.; Yang, Hannah; Zheng, Wei; Ziogas, Argyrios; Phelan, Catherine M.; Schildkraut, Joellen M.; Berchuck, Andrew; Goode, Ellen L.; Pharoah, Paul D. P.; Sellers, Thomas A.

2016-01-01

Rare and low frequency variants are not well covered in most germline genotyping arrays and are understudied in relation to epithelial ovarian cancer (EOC) risk. To address this gap, we used genotyping arrays targeting rarer protein-coding variation in 8,165 EOC cases and 11,619 controls from the international Ovarian Cancer Association Consortium (OCAC). Pooled association analyses were conducted at the variant and gene level for 98,543 variants directly genotyped through two exome genotyping projects. Only common variants that represent or are in strong linkage disequilibrium (LD) with previously-identified signals at established loci reached traditional thresholds for exome-wide significance (P  P≥5.0 ×10 − 7) were detected for rare and low-frequency variants at 16 novel loci. Four rare missense variants were identified (ACTBL2 rs73757391 (5q11.2), BTD rs200337373 (3p25.1), KRT13 rs150321809 (17q21.2) and MC2R rs104894658 (18p11.21)), but only MC2R rs104894668 had a large effect size (OR = 9.66). Genes most strongly associated with EOC risk included ACTBL2 (PAML = 3.23 × 10 − 5; PSKAT-o = 9.23 × 10 − 4) and KRT13 (PAML = 1.67 × 10 − 4; PSKAT-o = 1.07 × 10 − 5), reaffirming variant-level analysis. In summary, this large study identified several rare and low-frequency variants and genes that may contribute to EOC susceptibility, albeit with possible small effects. Future studies that integrate epidemiology, sequencing, and functional assays are needed to further unravel the unexplained heritability and biology of this disease. PMID:27378695

From monster to twin reversed arterial perfusion: a history of acardiac twins.

Science.gov (United States)

Obladen, Michael

2010-05-01

A human being born without heart and head, i.e., the acardius/acranius malformation, has been described since antiquity. Superstition and fear made it a mystical disorder, a sign of God's wrath. The inquisition ruled that acranic infants should not be baptized and located the soul in the brain. Acardia was not associated with twin gestation until the reports of Mery in 1720 and Winslow in 1740. In 1850, Meckel identified the pathogenetic mechanism as reversed perfusion due to large arterio-arterial and veno-venous anastomoses; he believed the heart would fail to develop or arrest during development, and the acardiac fetus would be maintained by arterial perfusion from the pump twin. In 1859, Claudius articulated that after normal initial development, the heart degenerates when reversed flow in the aorta leads to thrombosis. Today, it is assumed that both mechanisms may exist. With the advent of prenatal ultrasound diagnosis and radiofrequency ablation of the acardiac twin's circulation, it became possible to save the pump twin.

Coffee and smoking as risk factors of twin pregnancies

DEFF Research Database (Denmark)

Morales-Suárez-Varela, Maria M; Bech, Bodil Hammer; Christensen, Kaare

2007-01-01

their prepregnancy weight and height, coffee and alcohol intake, smoking habits, and potential confounding factors at early stages of pregnancy. We identified smoking (> 10 cigarettes/day) as a possible determinant of twinning, particularly for dizygotic twinning rates (same sex) and furthermore corroborated......Twinning rates have changed substantially over time for reasons that are only partly known. In this study we studied smoking, coffee and alcohol intake, and their possible interaction with obesity as potential determinants of twinning rates using data from the Danish National Birth Cohort between...... 1996 and 2002. We identified 82,985 pregnancies: 81,954 singleton and 1031 twins. For the twins we had data to classify 121 as monozygotic, 189 dizygotic (same sex), 313 dizygotic (opposite sex) but, 408 were of the same sex but with unknown zygosity. All mothers were interviewed about...

Integrative analysis of functional genomic annotations and sequencing data to identify rare causal variants via hierarchical modeling

Directory of Open Access Journals (Sweden)

Marinela eCapanu

2015-05-01

Full Text Available Identifying the small number of rare causal variants contributing to disease has beena major focus of investigation in recent years, but represents a formidable statisticalchallenge due to the rare frequencies with which these variants are observed. In thiscommentary we draw attention to a formal statistical framework, namely hierarchicalmodeling, to combine functional genomic annotations with sequencing data with theobjective of enhancing our ability to identify rare causal variants. Using simulations weshow that in all configurations studied, the hierarchical modeling approach has superiordiscriminatory ability compared to a recently proposed aggregate measure of deleteriousness,the Combined Annotation-Dependent Depletion (CADD score, supportingour premise that aggregate functional genomic measures can more accurately identifycausal variants when used in conjunction with sequencing data through a hierarchicalmodeling approach

'Biracial'-Looking Twins: A New Twin Type?/Twin Research: Twins with Cystic Teratomas; Sleep Quality and Body Mass Index; Previable Membrane Rupture/Print and Online Reports: Twins Born to a Sister Surrogate; NASA Twin Study; African-Cosmopolitan Twin Fashion Inspirations; Triplet Hockey Stars.

Science.gov (United States)

Segal, Nancy L

2017-06-01

Dizygotic (DZ) co-twins born to mothers and fathers from different racial or ethnic backgrounds often resemble one parent much more than the other. As such, these pairs comprise a unique subset of twins for investigating how others' responses to their different looks may affect their personalities and self-esteem. This article describes some of these twin pairs and some challenges of raising them, and suggests ways they may be used in research. Next, recent twin research on cystic teratomas, relations between sleep quality and body mass index, and previable membrane rupture is described. The final section concerns twins, twin studies, and related events in the media, namely: twins born to a sister surrogate, the NASA twin investigation, inspiring African-Cosmopolitan twins in fashion, and triplet Hockey Stars.

Remembering Irving I. Gottesman: Twin Research Colleague and Friend Extraordinaire/Research Studies: Face-Lift Technique Comparison in Identical Twins; Raising Preterm Twins; Fetal Behavior in Dichorionic Twin Pregnancies; Co-Bedding and Stress Reduction in Twins/Public Interest: Identical Co-Twins' Same Day Delivery; Teaching Twins in Bosnia; Twin Auctioneers; Sister, the Play.

Science.gov (United States)

Segal, Nancy L

2016-12-01

Dr Irving I. Gottesman, a colleague, friend, and long-time member of the International Society of Twin Studies passed away on June 29, 2016. His contributions to twin research and some personal reflections are presented to honor both the man and the memory. This tribute is followed by short reviews of twin research concerning differences between cosmetic surgical techniques, the rearing of preterm twins, behavioral observations of dichorionic fetal twins, and the outcomes of co-bedding twins with reference to stress reduction. Interesting and informative articles in the media describe identical co-twins who delivered infants on the same day, educational policies regarding twins in Bosnia and the United Kingdom, unusual practices of twin auctioneers, and a theatrical production, Sister, featuring identical twins in the leading roles.

Genome-wide association study identifies variants in HORMAD2 associated with tonsillectomy

DEFF Research Database (Denmark)

Feenstra, Bjarke; Bager, Peter; Liu, Xueping

2017-01-01

BACKGROUND: Inflammation of the tonsils is a normal response to infection, but some individuals experience recurrent, severe tonsillitis and massive hypertrophy of the tonsils in which case surgical removal of the tonsils may be considered. OBJECTIVE: To identify common genetic variants associate...... the molecular mechanisms underlying the genetic association involve general lymphoid hyper-reaction throughout the mucosa-associated lymphoid tissue system.......BACKGROUND: Inflammation of the tonsils is a normal response to infection, but some individuals experience recurrent, severe tonsillitis and massive hypertrophy of the tonsils in which case surgical removal of the tonsils may be considered. OBJECTIVE: To identify common genetic variants associated...... with tonsillectomy. METHODS: We used tonsillectomy information from Danish health registers and carried out a genome-wide association study comprising 1464 patients and 12 019 controls of Northwestern European ancestry, with replication in an independent sample set of 1575 patients and 1367 controls. RESULTS...

Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis

DEFF Research Database (Denmark)

Beecham, Ashley H; Patsopoulos, Nikolaos A; Xifara, Dionysia K

2013-01-01

Using the ImmunoChip custom genotyping array, we analyzed 14,498 subjects with multiple sclerosis and 24,091 healthy controls for 161,311 autosomal variants and identified 135 potentially associated regions (P...

[Adult twins].

Science.gov (United States)

Charlemaine, Christiane

2006-12-31

This paper explores the deep roots of closeness that twins share in their youngest age and their effect on their destiny at the adult age. Psychologists believe the bond between twins begins in utero and develops throughout the twins' lives. The four patterns of twinship described show that the twin bond is determined by the quality of parenting that twins receive in their infancy and early childhood. Common problems of adult twins bring about difficulties to adapt in a non-twin world. The nature versus nurture controversy has taken on new life focusing on inter-twin differences and the importance of parent-child interaction as fundamental to the growth and development of personality.

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

NARCIS (Netherlands)

van Leeuwen, E.M.; Karssen, L.C.; Deelen, J.; Isaacs, A.; Medina-Gomez, C.; Mbarek, H.; Kanterakis, A.; Trompet, S.; Postmus, I.; Verweij, N.; van Enckevort, D.; Huffman, J.E.; White, C.C.; Feitosa, M.F.; Bartz, T.M.; Manichaikul, A.; Joshi, P.K.; Peloso, G.M.; Deelen, P.; Dijk, F.; Willemsen, G.; de Geus, E.J.C.; Milaneschi, Y.; Penninx, B.W.J.H.; Francioli, L.C.; Menelaou, A.; Pulit, S.L.; Rivadeneira, F.; Hofman, A.; Oostra, B.A.; Franco, O.H.; Mateo Leach, I.; Beekman, M.; de Craen, A.J.; Uh, H.W.; Trochet, H.; Hocking, L.J.; Porteous, D.J.; Sattar, N.; Packard, C.J.; Buckley, B.M.; Brody, J.A.; Bis, J.C.; Rotter, J.I.; Mychaleckyj, J.C.; Campbell, H.; Duan, Q.; Lange, L.A.; Wilson, J.F.; Hayward, C.; Polasek, O.; Vitart, V.; Rudan, I.; Wright, A.F.; Rich, S.S.; Psaty, B.M.; Borecki, I.B.; Kearney, P.M.; Stott, D.J.; Cupples, L.A.; Jukema, J.W.; van der Harst, P.; Sijbrands, E.J.; Hottenga, J.J.; Uitterlinden, A.G.; Swertz, M.A.; van Ommen, G.J.B; Bakker, P.I.W.; Slagboom, P.E.; Boomsma, D.I.; Wijmenga, C.; van Duijn, C.M.

2015-01-01

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

Novel Genetic Variants of Sporadic Atrial Septal Defect (ASD) in a Chinese Population Identified by Whole-Exome Sequencing (WES).

Science.gov (United States)

Liu, Yong; Cao, Yu; Li, Yaxiong; Lei, Dongyun; Li, Lin; Hou, Zong Liu; Han, Shen; Meng, Mingyao; Shi, Jianlin; Zhang, Yayong; Wang, Yi; Niu, Zhaoyi; Xie, Yanhua; Xiao, Benshan; Wang, Yuanfei; Li, Xiao; Yang, Lirong; Wang, Wenju; Jiang, Lihong

2018-03-05

BACKGROUND Recently, mutations in several genes have been described to be associated with sporadic ASD, but some genetic variants remain to be identified. The aim of this study was to use whole-exome sequencing (WES) combined with bioinformatics analysis to identify novel genetic variants in cases of sporadic congenital ASD, followed by validation by Sanger sequencing. MATERIAL AND METHODS Five Han patients with secundum ASD were recruited, and their tissue samples were analyzed by WES, followed by verification by Sanger sequencing of tissue and blood samples. Further evaluation using blood samples included 452 additional patients with sporadic secundum ASD (212 male and 240 female patients) and 519 healthy subjects (252 male and 267 female subjects) for further verification by a multiplexed MassARRAY system. Bioinformatic analyses were performed to identify novel genetic variants associated with sporadic ASD. RESULTS From five patients with sporadic ASD, a total of 181,762 genomic variants in 33 exon loci, validated by Sanger sequencing, were selected and underwent MassARRAY analysis in 452 patients with ASD and 519 healthy subjects. Three loci with high mutation frequencies, the 138665410 FOXL2 gene variant, the 23862952 MYH6 gene variant, and the 71098693 HYDIN gene variant were found to be significantly associated with sporadic ASD (PASD (PASD, and supported the use of WES and bioinformatics analysis to identify disease-associated mutations.

Risk of epilepsy in opposite-sex and same-sex twins

DEFF Research Database (Denmark)

Mao, Yanyan; Ahrenfeldt, Linda Juel; Christensen, Kaare

2018-01-01

Background: There is a complex interaction between female and male sex hormones and the risk of epilepsy. Whether prenatal exposure to higher levels of sex hormones affects the development of epilepsy in childhood or later in life is not well known. The sex hormone environment of fetuses may...... be affected by the sex of the co-twin. We estimated the risk of epilepsy for twins with an opposite-sex (OS) co-twin compared with twins with a same-sex (SS) co-twin. Methods: From the Danish Twin Registry, we identified OS female twins (n = 11,078), SS female twins (n = 19,186), OS male twins (n = 11...

Do MZ twins have discordant experiences of friendship? A qualitative hypothesis-generating MZ twin differences study

Science.gov (United States)

Moran, Nicola; Plomin, Robert

2017-01-01

Using a qualitative monozygotic (MZ) twin differences design we explored whether adolescent MZ twins report discordant peer relationships and, if so, whether they perceive them as causes, consequences or correlates of discordant behaviour. We gathered free-response questionnaire data from 497 families and conducted in-depth telephone interviews with 97 of them. Within this dataset n = 112 families (23% of the sample) described discordant peer relationships. Six categories of discordance were identified (peer victimisation, peer rejection, fewer friends, different friends, different attitudes to friendship and dependence on co-twin). Participants described peer relationship discordance arising as a result of chance occurrences, enhanced vulnerability in one twin or discordant behaviour. Consequences of discordant peer relationships were seen as discordance in self-confidence, future plans, social isolation, mental health and interests. In all cases the twin with worse peer experiences was seen as having a worse outcome. Specific hypotheses are presented. PMID:28727730

The Fourth International Network of Twin Registries: Overview from Osaka/Research Reviews: Familial Fraternal Twinning; Twin Study of Masculine Faces; Physical Aggression and Epigenetics; Prenatal Education for Parents of Twins/Current Events: 2016 Guinness Book of World Records; Oldest Living Male Twins; Twins Reunited at Sixty-Nine; Panda Twins; Twins.com.

Science.gov (United States)

Segal, Nancy L

2015-12-01

The 4th International Network of Twin Registries (INTR) Consortium Meeting took place in Osaka, Japan, September 28-29, 2015. The venue was the Osaka Medical Center for Medical Innovation and Translational Research. An overview of presentations and other activities is provided. Next, 1930s research on familial fraternal twinning, preference for masculine faces, physical aggression and epigenetics, and a prenatal education program for parents of multiples are described. Current twin-related events include the 2016 Guinness Book of World Records (GWR), the oldest living male twins, newly reunited twins, the birth of panda twins and a controversial twin-based website.

Fetal behavior in normal dichorionic twin pregnancy

NARCIS (Netherlands)

Mulder, E. J. H.; Derks, J. B.; de Laat, M. W. M.; Visser, G. H. A.

2012-01-01

Objectives: A prospective study was performed to compare fetal behavioral development in healthy dichorionic twins and singletons, and identify twin intra-pair associations (synchrony) of fetal movements and rest-activity cycles using different criteria to define synchrony. Subjects and methods:

The Placenta in Twin-to-Twin Transfusion Syndrome and Twin Anemia Polycythemia Sequence.

Science.gov (United States)

Couck, Isabel; Lewi, Liesbeth

2016-06-01

Twin-to-twin transfusion syndrome (TTTS) and twin anemia polycythemia sequence (TAPS) are complications unique to monochorionic twin pregnancies and their shared circulation. Both are the result of the transfusion imbalance in the intertwin circulation. TTTS is characterized by an amniotic fluid discordance, whereas in TAPS, there is a severe discordance in hemoglobin levels. The article gives an overview of the typical features of TTTS and TAPS placentas.

Screening of whole genome sequences identified high-impact variants for stallion fertility.

Science.gov (United States)

Schrimpf, Rahel; Gottschalk, Maren; Metzger, Julia; Martinsson, Gunilla; Sieme, Harald; Distl, Ottmar

2016-04-14

g.37455302G>A in NOTCH1 with the de-regressed estimated breeding values of the paternal component of the pregnancy rate per estrus (EBV-PAT). For 9 high-impact variants within the genes CFTR, OVGP1, FBXO43, TSSK6, PKD1, FOXP1, TCP11, SPATA31E1 and NOTCH1 (g.37453246G>C) absence of the homozygous mutant genotype in the validation sample of all 337 fertile stallions was obvious. Therefore, these variants were considered as potentially deleterious factors for stallion fertility. In conclusion, this study revealed 17 genetic variants with a predicted high damaging effect on protein structure and missing homozygous mutant genotype. The g.37455302G>A NOTCH1 variant was identified as a significant stallion fertility locus in Hanoverian stallions and further 9 candidate fertility loci with missing homozygous mutant genotypes were validated in a panel including 19 horse breeds. To our knowledge this is the first study in horses using next generation sequencing data to uncover strong candidate factors for stallion fertility.

Antenatal management of twin-twin transfusion syndrome and twin anemia-polycythemia sequence.

Science.gov (United States)

Slaghekke, Femke; Zhao, Depeng P; Middeldorp, Johanna M; Klumper, Frans J; Haak, Monique C; Oepkes, Dick; Lopriore, Enrico

2016-08-01

Twin-twin transfusion syndrome (TTTS) and twin anemia polycythemia sequence (TAPS) are severe complications in monochorionic twin pregnancies associated with high mortality and morbidity risk if left untreated. Both diseases result from imbalanced inter-twin blood transfusion through placental vascular anastomoses. This review focuses on the differences in antenatal management between TTTS and TAPS. Expert commentary: The optimal management for TTTS is fetoscopic laser coagulation of the vascular anastomoses, preferably using the Solomon technique in which the whole vascular equator is coagulated. The Solomon technique is associated with a reduction of residual anastomosis and a reduction in post-operative complications. The optimal management for TAPS is not clear and includes expectant management, intra-uterine transfusion with or without partial exchange transfusion and fetoscopic laser surgery.

A Possible Twin: The 1960s Twin Study Revisited/Twin Research: Twin-to-Twin Heart Transplantation; Distinguishing Monozygotic Twins; Twin Conceptions via Oocyte Donation; Factors Affecting Craniofacial Traits/In the Media: Triplet Delivery in the UK; Conjoined Twins and the Concept of Self; Colombian Twin Trainers; Skin Grafting to Save an Identical Co-Twin; Lack of Physical Flaws in Dolly the Cloned Sheep; Possible Conjoined Twins of Opposite-Sex; Passing of the Remaining Twin From the World's Longest Separated Pair.

Science.gov (United States)

Segal, Nancy L

2018-04-01

This article begins with the story of a 51-year-old Los Angeles, California man, Justin Goldberg, whose daughter caught a glimpse of his striking look-alike at a popular market. Many people have so-called doppelgängers, but this occurrence is especially intriguing - the individual in question, born in New York City in the mid-1960s to an unwed mother, was an adoptee placed by the Louise Wise Adoption Agency. This agency, under the guidance of a prominent psychiatrist, decided to place twins in separate homes. Some of these twin children were part of a controversial child development study that was hidden from them and their parents. Next, recent and current twin research on heart transplantation, distinguishing monozygotic co-twins, twin conceptions via oocyte donation and factors affecting craniofacial traits are summarized. The article concludes with highlights on twins in the media, specifically, a triplet delivery in the United Kingdom, self-concept and consciousness in conjoined twins, Colombian twin trainers, skin grafting to save an identical co-twin, lack of physical flaws in Dolly the cloned sheep, possible opposite-sex conjoined twins, and the passing of the remaining twin from the world's longest separated pair.

Variant-aware saturating mutagenesis using multiple Cas9 nucleases identifies regulatory elements at trait-associated loci.

Science.gov (United States)

Canver, Matthew C; Lessard, Samuel; Pinello, Luca; Wu, Yuxuan; Ilboudo, Yann; Stern, Emily N; Needleman, Austen J; Galactéros, Frédéric; Brugnara, Carlo; Kutlar, Abdullah; McKenzie, Colin; Reid, Marvin; Chen, Diane D; Das, Partha Pratim; A Cole, Mitchel; Zeng, Jing; Kurita, Ryo; Nakamura, Yukio; Yuan, Guo-Cheng; Lettre, Guillaume; Bauer, Daniel E; Orkin, Stuart H

2017-04-01

Cas9-mediated, high-throughput, saturating in situ mutagenesis permits fine-mapping of function across genomic segments. Disease- and trait-associated variants identified in genome-wide association studies largely cluster at regulatory loci. Here we demonstrate the use of multiple designer nucleases and variant-aware library design to interrogate trait-associated regulatory DNA at high resolution. We developed a computational tool for the creation of saturating-mutagenesis libraries with single or multiple nucleases with incorporation of variants. We applied this methodology to the HBS1L-MYB intergenic region, which is associated with red-blood-cell traits, including fetal hemoglobin levels. This approach identified putative regulatory elements that control MYB expression. Analysis of genomic copy number highlighted potential false-positive regions, thus emphasizing the importance of off-target analysis in the design of saturating-mutagenesis experiments. Together, these data establish a widely applicable high-throughput and high-resolution methodology to identify minimal functional sequences within large disease- and trait-associated regions.

Urticaria in monozygotic and dizygotic twins

DEFF Research Database (Denmark)

Thomsen, Simon Francis; van der Sluis, Sophie; Kyvik, Kirsten Ohm

2012-01-01

Aim. To identify risk factors for urticaria, to determine the relative proportion of the susceptibility to urticaria that is due to genetic factors in an adult clinical twin sample, and to further determine whether the genetic susceptibility to urticaria overlaps with the genetic susceptibility...... to atopic diseases. Methods. A total of 256 complete twin pairs and 63 single twins, who were selected from sibships with self-reported asthma via a questionnaire survey of 21,162 adult twins from the Danish Twin Registry, were clinically interviewed about a history of urticaria and examined for atopic...... diseases. Data were analysed with Cox proportional hazards regression and variance components models. Results. A total of 151 individuals (26%) had a history of urticaria, whereas 24 (4%) had had symptoms within the past year. Female sex, HR = 2.09 (1.46-2.99), P = 0.000; hay fever, HR = 1.92 (1...

Salivary cortisol in unaffected twins discordant for affective disorder

DEFF Research Database (Denmark)

Vinberg, Maj; Bennike, Bente; Kyvik, Kirsten Ohm

2008-01-01

. In conclusion, a high genetic liability to affective disorder was associated with a higher evening cortisol level, but not with awakening cortisol level. Future prospective family, high-risk and twin studies are needed to decide whether abnormalities in the HPA axis can be identified as an endophenotype......Dysfunction in the hypothalamic-pituitary-adrenal (HPA) axis has been proposed as a biological endophenotype for affective disorders. In the present study the hypothesis that a high genetic liability to affective disorder is associated with higher cortisol levels was tested in a cross......-sectional high-risk study. Healthy monozygotic (MZ) and dizygotic (DZ) twins with (High-Risk twins) and without (Low-Risk twins) a co-twin history of affective disorder were identified through nationwide registers. Awakening and evening salivary cortisol levels were compared between the 190 High- and Low...

MZ twin pairs or MZ singletons in population family-based GWAS? More power in pairs

NARCIS (Netherlands)

Minica, C.C.; Boomsma, D.I.; Vink, J.M.; Dolan, C.V.

2014-01-01

Family-based genome-wide association studies (GWAS) involve testing the genetic association of (many) genetic variants with the phenotype of interest, while taking into account the relatedness among family members. Occasionally in family-based GWAS, including monozygotic (MZ) twins, the data from

Highlights from the 15th International Congress of Twin Studies/Twin Research: Differentiating MZ Co-twins Via SNPs; Mistaken Infant Twin-Singleton Hospital Registration; Narcolepsy With Cataplexy; Hearing Loss and Language Learning/Media Mentions: Broadway Musical Recalls Conjoined Hilton Twins; High Fashion Pair; Twins Turn 102; Insights From a Conjoined Twin Survivor.

Science.gov (United States)

Segal, Nancy L

2015-02-01

Highlights from the 15th International Congress of Twin Studies are presented. The congress was held November 16-19, 2014 in Budapest, Hungary. This report is followed by summaries of research addressing the differentiation of MZ co-twins by single nucleotide polymorphisms (SNPs), an unusual error in infant twin-singleton hospital registration, twins with childhood-onset narcolepsy with cataplexy, and the parenting effects of hearing loss in one co-twin. Media interest in twins covers a new Broadway musical based on the conjoined twins Violet and Daisy Hilton, male twins becoming famous in fashion, twins who turned 102 and unique insights from a conjoined twin survivor. This article is dedicated to the memory of Elizabeth (Liz) Hamel, DZA twin who met her co-twin for the first time at age seventy-eight years. Liz and her co-twin, Ann Hunt, are listed in the 2015 Guinness Book of Records as the longest separated twins in the world.

Fasting plasma total ghrelin concentrations in monozygotic twins discordant for obesity.

Science.gov (United States)

Leskelä, Piia; Ukkola, Olavi; Vartiainen, Johanna; Rönnemaa, Tapani; Kaprio, Jaakko; Bouchard, Claude; Kesäniemi, Y Antero

2009-02-01

Ghrelin is a hormone that is involved in the regulation of food intake. Neuronal, endocrine, and genetic factors have been shown to regulate plasma ghrelin levels; but the determinants of fasting ghrelin concentrations are not yet fully understood. The main aim was to explore the roles of adiposity and genetic differences in determining fasting plasma total ghrelin levels. We measured total ghrelin levels in a population of 23 monozygotic twin pairs discordant for obesity. In addition, 2 variants of ghrelin gene, namely, Arg51Gln and Leu72Met, were genotyped in 3 populations of monozygotic twin pairs: 23 obesity-discordant, 43 lean-concordant, and 46 obesity-concordant twin pairs. In discordant twins, lean co-twins had higher fasting plasma total ghrelin levels (950 pg/mL, SD = 328 pg/mL) than obese twins (720 pg/mL, SD = 143 pg/mL; P = .003). Arg51Gln-polymorphism of the ghrelin gene was equally distributed between the twin groups. However, there were significant differences in genotype frequencies at the Leu72Met polymorphism between the discordant and obese-concordant groups (P = .003) and between the discordant and lean-concordant groups (P = .011), but not between the 2 concordant groups. In the discordant group, there were fewer Met carriers (4%) than among the obese (17%) or the lean-concordant groups (15%). Plasma total ghrelin levels are affected by acquired obesity independent of genetic background. The Leu72 allele is particularly common among monozygotic twins discordant for obesity, suggesting that this ghrelin allele is more permissive in the regulation of energy balance. The ghrelin gene may thus play a role in the regulation of variability of body weight, such that Leu72 allele carriers are more prone to weight variability in response to environmental factors.

Twin-twin transfusion syndrome: neurodevelopment of infants treated with laser surgery

Directory of Open Access Journals (Sweden)

Denise Campos

2016-04-01

Full Text Available ABSTRACT Objective To assess the neurodevelopmental functions of survivors of twin-twin transfusion syndrome (TTTS treated by fetoscopic laser coagulation (FLC, during the first year of life, comparing them to a control group; and to verify the influence of specific variables on neurodevelopment. Method This was a prospective, longitudinal study. The sample comprised 33 monochorionic diamniotic twins who underwent FLC for treatment of TTTS and 22 full-term infants of single-fetus pregnancies. Bayley Scales of Infant and Toddler Development Screening Test were used for evaluation. Prenatal, perinatal and postnatal information were obtained. Results There was an increased frequency of infants in the TTTS group with inadequate performance compared to the control group. The identified variables (fetal donor, low economic income and cardiorespiratory disease negatively impacted expressive communication and fine motor skills. Conclusion Although through follow-up is recommended in all TTTS survivors, particular attention is required for the high-risk group as defined in this study.

Identifying genetic variants that affect viability in large cohorts.

Directory of Open Access Journals (Sweden)

Hakhamanesh Mostafavi

2017-09-01

Full Text Available A number of open questions in human evolutionary genetics would become tractable if we were able to directly measure evolutionary fitness. As a step towards this goal, we developed a method to examine whether individual genetic variants, or sets of genetic variants, currently influence viability. The approach consists in testing whether the frequency of an allele varies across ages, accounting for variation in ancestry. We applied it to the Genetic Epidemiology Research on Adult Health and Aging (GERA cohort and to the parents of participants in the UK Biobank. Across the genome, we found only a few common variants with large effects on age-specific mortality: tagging the APOE ε4 allele and near CHRNA3. These results suggest that when large, even late-onset effects are kept at low frequency by purifying selection. Testing viability effects of sets of genetic variants that jointly influence 1 of 42 traits, we detected a number of strong signals. In participants of the UK Biobank of British ancestry, we found that variants that delay puberty timing are associated with a longer parental life span (P~6.2 × 10-6 for fathers and P~2.0 × 10-3 for mothers, consistent with epidemiological studies. Similarly, variants associated with later age at first birth are associated with a longer maternal life span (P~1.4 × 10-3. Signals are also observed for variants influencing cholesterol levels, risk of coronary artery disease (CAD, body mass index, as well as risk of asthma. These signals exhibit consistent effects in the GERA cohort and among participants of the UK Biobank of non-British ancestry. We also found marked differences between males and females, most notably at the CHRNA3 locus, and variants associated with risk of CAD and cholesterol levels. Beyond our findings, the analysis serves as a proof of principle for how upcoming biomedical data sets can be used to learn about selection effects in contemporary humans.

Genetic mapping and exome sequencing identify variants associated with five novel diseases.

Directory of Open Access Journals (Sweden)

Erik G Puffenberger

Full Text Available The Clinic for Special Children (CSC has integrated biochemical and molecular methods into a rural pediatric practice serving Old Order Amish and Mennonite (Plain children. Among the Plain people, we have used single nucleotide polymorphism (SNP microarrays to genetically map recessive disorders to large autozygous haplotype blocks (mean = 4.4 Mb that contain many genes (mean = 79. For some, uninformative mapping or large gene lists preclude disease-gene identification by Sanger sequencing. Seven such conditions were selected for exome sequencing at the Broad Institute; all had been previously mapped at the CSC using low density SNP microarrays coupled with autozygosity and linkage analyses. Using between 1 and 5 patient samples per disorder, we identified sequence variants in the known disease-causing genes SLC6A3 and FLVCR1, and present evidence to strongly support the pathogenicity of variants identified in TUBGCP6, BRAT1, SNIP1, CRADD, and HARS. Our results reveal the power of coupling new genotyping technologies to population-specific genetic knowledge and robust clinical data.

How to identify twins at low risk of spontaneous preterm delivery

DEFF Research Database (Denmark)

Sperling, L; Kiil, C; Larsen, Lene Unmack

2005-01-01

delivery at different cut-off levels of cervical length were determined. RESULTS: Eighty-nine percent of the twins had dichorionic placentation and 58% were conceived after assisted reproduction. The rate of spontaneous preterm delivery was 2.3% (1.5% for dichorionic (DC) and 9.1% for (MC) monochorionic...

Molecular dynamics simulation of albite twinning and pericline twinning in low albite

International Nuclear Information System (INIS)

Li, Bin; Knowles, Kevin M

2013-01-01

Two twinning laws, the albite law and the pericline law, are the predominant growth twinning modes in triclinic plagioclase feldspars such as low albite, NaAlSi 3 O 8 , in which the aluminum and silicon atoms are in an ordered arrangement on the tetrahedral sites of the aluminosilicate framework. In the terminology used formally to describe deformation twinning in a triclinic lattice, these twin laws can be described as Type I and Type II twin laws, respectively, with the pericline twin law being conjugate to the albite twin law. In this study, twin boundaries have been constructed for low albite according to these two twinning laws and studied by molecular dynamics simulation. The results show that suitably constructed twin boundary models are quite stable for both albite twinning and pericline twinning during molecular dynamics simulation. The calculated twin boundary energy of an albite twin is significantly lower than that of a pericline twin, in accord with the experimental observation that albite twinning is the more commonly observed mode seen in plagioclase feldspars. The results of the molecular dynamics simulations also agree with conclusions from the prior work of Starkey that glide twinning in low albite is not favoured energetically. (paper)

Art for twins: Yorùbá artists and their statues/twin research studies: twins' education and conceptions; diurnal preference; inherited eye diseases; ultrasound counseling when twins are conjoined/popular twin reports: twin sisters (the film); rare pregnancy; diet test; French twins reared apart and reunited.

Science.gov (United States)

Segal, Nancy L

2014-06-01

The Yorùbá of Nigeria are well known for their high twinning rate and the statues they create to commemorate deceased twins. An impressive collection of this artwork was displayed at the University of California's Fowler Museum in Los Angeles between October 13, 2013 and March 2, 2014. An overview of this exhibit is provided. Next, twin research on maternal education and conception, diurnal preference, inherited eye diseases, and ultrasound counseling for couples with conjoined twins are briefly summarized. This article concludes with a discussion of media-based items related to twins. The topics include an award-winning twin film, a rare pregnancy, a diet test, and the separation and chance reunion of monozygotic female twins.

Exome-Wide Association Study Identifies New Low-Frequency and Rare UGT1A1 Coding Variants and UGT1A6 Coding Variants Influencing Serum Bilirubin in Elderly Subjects

Science.gov (United States)

Oussalah, Abderrahim; Bosco, Paolo; Anello, Guido; Spada, Rosario; Guéant-Rodriguez, Rosa-Maria; Chery, Céline; Rouyer, Pierre; Josse, Thomas; Romano, Antonino; Elia, Maurizzio; Bronowicki, Jean-Pierre; Guéant, Jean-Louis

2015-01-01

Abstract Genome-wide association studies (GWASs) have identified loci contributing to total serum bilirubin level. However, no exome-wide approaches have been performed to address this question. Using exome-wide approach, we assessed the influence of protein-coding variants on unconjugated, conjugated, and total serum bilirubin levels in a well-characterized cohort of 773 ambulatory elderly subjects from Italy. Coding variants were replicated in 227 elderly subjects from the same area. We identified 4 missense rare (minor allele frequency, MAF bilirubin level (P = 2.34 × 10−34, P = 7.02 × 10−34, and P = 8.27 × 10−34), as well as unconjugated, and conjugated bilirubin levels. We also identified UGT1A6 variants in association with total (rs6759892, p.Ser7Ala, P = 1.98 × 10−26; rs2070959, p.Thr181Ala, P = 2.87 × 10−27; and rs1105879, p.Arg184Ser, P = 3.27 × 10−29), unconjugated, and conjugated bilirubin levels. All UGT1A1 intronic variants (rs887829, rs6742078, and rs4148325) and UGT1A6 coding variants (rs6759892, rs2070959, and rs1105879) were significantly associated with gallstone-related cholecystectomy risk. The UGT1A6 variant rs2070959 (p.Thr181Ala) was associated with the highest risk of gallstone–related cholecystectomy (OR, 4.58; 95% CI, 1.58–13.28; P = 3.21 × 10−3). Using an exome-wide approach we identified coding variants on UGT1A1 and UGT1A6 genes in association with serum bilirubin level and hyperbilirubinemia risk in elderly subjects. UGT1A1 intronic single-nucleotide polymorphisms (SNPs) (rs6742078, rs887829, rs4148324) serve as proxy markers for the low-frequency and rare UGT1A1 variants, thereby providing mechanistic explanation to the relationship between UGT1A1 intronic SNPs and the UGT1A1 enzyme activity. UGT1A1 and UGT1A6 variants might be potentially associated with gallstone-related cholecystectomy risk. PMID:26039129

Common genetic variants associated with cognitive performance identified using the proxy-phenotype method

NARCIS (Netherlands)

C.A. Rietveld (Niels); T. Esko (Tõnu); G. Davies (Gail); T.H. Pers (Tune); P. Turley (Patrick); B. Benyamin (Beben); C.F. Chabris (Christopher F.); V. Emilsson (Valur); A.D. Johnson (Andrew); J.J. Lee (James J.); C. de Leeuw (Christiaan); R.E. Marioni (Riccardo); S.E. Medland (Sarah Elizabeth); M. Miller (Mike); O. Rostapshova (Olga); S.J. van der Lee (Sven); A.A.E. Vinkhuyzen (Anna A.); N. Amin (Najaf); D. Conley (Dalton); J. Derringer; C.M. van Duijn (Cornelia); R.S.N. Fehrmann (Rudolf); L. Franke (Lude); E.L. Glaeser (Edward L.); N.K. Hansell (Narelle); C. Hayward (Caroline); W.G. Iacono (William); C.A. Ibrahim-Verbaas (Carla); V.W.V. Jaddoe (Vincent); J. Karjalainen (Juha); D. Laibson (David); P. Lichtenstein (Paul); D.C. Liewald (David C.); P.K. Magnusson (Patrik); N.G. Martin (Nicholas); M. McGue (Matt); G. Mcmahon (George); N.L. Pedersen (Nancy); S. Pinker (Steven); D.J. Porteous (David J.); D. Posthuma (Danielle); F. Rivadeneira Ramirez (Fernando); B.H. Smithk (Blair H.); J.M. Starr (John); H.W. Tiemeier (Henning); N.J. Timpsonm (Nicholas J.); M. Trzaskowskin (Maciej); A.G. Uitterlinden (André); F.C. Verhulst (Frank); M.E. Ward (Mary); M.J. Wright (Margaret); G.D. Smith; I.J. Deary (Ian J.); M. Johannesson (Magnus); R. Plomin (Robert); P.M. Visscher (Peter); D.J. Benjamin (Daniel J.); D. Cesarini (David); Ph.D. Koellinger (Philipp)

2014-01-01

textabstractWe identify common genetic variants associated with cognitive performance using a two-stage approach, which we call the proxyphenotype method. First, we conduct a genome-wide association study of educational attainment in a large sample (n = 106,736), which produces a set of 69

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

Science.gov (United States)

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.; Adrienne Cupples, L.; Neerincx, Pieter B.T.; 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.; Byelas, Heorhiy; den Dunnen, Johan T.; Dijkstra, Martijn; Amin, Najaf; Joeri van der Velde, K.; 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.; 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.

2015-01-01

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 <6.61 × 10−4), 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. PMID:25751400

Multiplexed resequencing analysis to identify rare variants in pooled DNA with barcode indexing using next-generation sequencer.

Science.gov (United States)

Mitsui, Jun; Fukuda, Yoko; Azuma, Kyo; Tozaki, Hirokazu; Ishiura, Hiroyuki; Takahashi, Yuji; Goto, Jun; Tsuji, Shoji

2010-07-01

We have recently found that multiple rare variants of the glucocerebrosidase gene (GBA) confer a robust risk for Parkinson disease, supporting the 'common disease-multiple rare variants' hypothesis. To develop an efficient method of identifying rare variants in a large number of samples, we applied multiplexed resequencing using a next-generation sequencer to identification of rare variants of GBA. Sixteen sets of pooled DNAs from six pooled DNA samples were prepared. Each set of pooled DNAs was subjected to polymerase chain reaction to amplify the target gene (GBA) covering 6.5 kb, pooled into one tube with barcode indexing, and then subjected to extensive sequence analysis using the SOLiD System. Individual samples were also subjected to direct nucleotide sequence analysis. With the optimization of data processing, we were able to extract all the variants from 96 samples with acceptable rates of false-positive single-nucleotide variants.

Myopathy With SQSTM1 and TIA1 Variants: Clinical and Pathological Features

Directory of Open Access Journals (Sweden)

Zhiyv Niu

2018-03-01

Full Text Available ObjectiveThe aim of this study is to identify the molecular defect of three unrelated individuals with late-onset predominant distal myopathy; to describe the spectrum of phenotype resulting from the contributing role of two variants in genes located on two different chromosomes; and to highlight the underappreciated complex forms of genetic myopathies.Patients and methodsClinical and laboratory data of three unrelated probands with predominantly distal weakness manifesting in the sixth-seventh decade of life, and available affected and unaffected family members were reviewed. Next-generation sequencing panel, whole exome sequencing, and targeted analyses of family members were performed to elucidate the genetic etiology of the myopathy.ResultsGenetic analyses detected two contributing variants located on different chromosomes in three unrelated probands: a heterozygous pathogenic mutation in SQSTM1 (c.1175C>T, p.Pro392Leu and a heterozygous variant in TIA1 (c.1070A>G, p.Asn357Ser. The affected fraternal twin of one proband also carries both variants, while the unaffected family members harbor one or none. Two unrelated probands (family 1, II.3, and family 3, II.1 have a distal myopathy with rimmed vacuoles that manifested with index extensor weakness; the other proband (family 2, I.1 has myofibrillar myopathy manifesting with hypercapnic respiratory insufficiency and distal weakness.ConclusionThe findings indicate that all the affected individuals have a myopathy associated with both variants in SQSTM1 and TIA1, respectively, suggesting that the two variants determine the phenotype and likely functionally interact. We speculate that the TIA1 variant is a modifier of the SQSTM1 mutation. We identify the combination of SQSTM1 and TIA1 variants as a novel genetic defect associated with myofibrillar myopathy and suggest to consider sequencing both genes in the molecular investigation of myopathy with rimmed vacuoles and myofibrillar myopathy

Myopathy With SQSTM1 and TIA1 Variants: Clinical and Pathological Features.

Science.gov (United States)

Niu, Zhiyv; Pontifex, Carly Sabine; Berini, Sarah; Hamilton, Leslie E; Naddaf, Elie; Wieben, Eric; Aleff, Ross A; Martens, Kristina; Gruber, Angela; Engel, Andrew G; Pfeffer, Gerald; Milone, Margherita

2018-01-01

The aim of this study is to identify the molecular defect of three unrelated individuals with late-onset predominant distal myopathy; to describe the spectrum of phenotype resulting from the contributing role of two variants in genes located on two different chromosomes; and to highlight the underappreciated complex forms of genetic myopathies. Clinical and laboratory data of three unrelated probands with predominantly distal weakness manifesting in the sixth-seventh decade of life, and available affected and unaffected family members were reviewed. Next-generation sequencing panel, whole exome sequencing, and targeted analyses of family members were performed to elucidate the genetic etiology of the myopathy. Genetic analyses detected two contributing variants located on different chromosomes in three unrelated probands: a heterozygous pathogenic mutation in SQSTM1 (c.1175C>T, p.Pro392Leu) and a heterozygous variant in TIA1 (c.1070A>G, p.Asn357Ser). The affected fraternal twin of one proband also carries both variants, while the unaffected family members harbor one or none. Two unrelated probands (family 1, II.3, and family 3, II.1) have a distal myopathy with rimmed vacuoles that manifested with index extensor weakness; the other proband (family 2, I.1) has myofibrillar myopathy manifesting with hypercapnic respiratory insufficiency and distal weakness. The findings indicate that all the affected individuals have a myopathy associated with both variants in SQSTM1 and TIA1 , respectively, suggesting that the two variants determine the phenotype and likely functionally interact. We speculate that the TIA1 variant is a modifier of the SQSTM1 mutation. We identify the combination of SQSTM1 and TIA1 variants as a novel genetic defect associated with myofibrillar myopathy and suggest to consider sequencing both genes in the molecular investigation of myopathy with rimmed vacuoles and myofibrillar myopathy although additional studies are needed to investigate the

Risk factors for asthma in young adults: a co-twin control study

DEFF Research Database (Denmark)

Thomsen, SF; Ulrik, Charlotte Suppli; Kyvik, KO

2006-01-01

BACKGROUND: The liability to asthma is influenced both by genetic and environmental factors. The objective of this study was to identify risk factors for asthma in young adult twin pairs during an 8-year period. METHODS: From the birth cohorts 1953-1982 of the Danish Twin Registry, 6,090 twin pairs....... Pairs in which only one twin developed asthma -- discordant pairs -- were identified and conditional logistic regression was applied to detect effects of risk factors. RESULTS: A total of 126 monozygotic (MZ) and 273 dizygotic (DZ) discordant twin pairs were identified. In MZ twins hay fever (OR = 3...... and females = 0.54, 95% CI: 0.36-0.80, P = 0.002), and increasing levels of body mass index (BMI; OR per unit = 1.11, 95% CI: 1.02-1.20, P = 0.009) were significant predictors of asthma. CONCLUSIONS: Hay fever, eczema, female sex, exercise and increasing levels of BMI were risk factors for asthma in young...

Therapeutic modalities of twin to twin transfusion syndrome

Directory of Open Access Journals (Sweden)

Šulović N.

2015-01-01

Full Text Available Twin to twin transfusion syndrome (TTTTS accounts for approximately 10% of monochorionic twin pregnancies and, if left untreated, is associated with high morbidity and mortality rate. A net transfusion of blood flow from one fetus (donor twin to the other (recipient twin via placental vascular anastomoses has been supposed as the major etiology of TTTTS. The donor twin becomes hypovolemic and oliguria, oligohydramnios, and a variable degree of growth restriction develop, whereas the recipient twin manifests polyuria, polyhydramnios, and hydrops in response to hypervolemia. TTTTS can be treated by either serial amniocentesis or selective fetoscopic laser coagulation of the communicating vessels. The rationale for removal of large volumes of amniotic fluid is to prevent preterm delivery secondary to polyhydramnios and to improve fetal circulation by reducing pressure on the chorionic plate. On the other hand, the goal of laser therapy is to occlude vascular anastomoses, thereby interrupting intertwin blood exchange. Although laser treatment is associated with increased survival rate and reduced neurologic complications, compared with amnioreduction, it requires highly specialized centers, whereas serial amniocentesis has the advantage of being performed worldwide. Therefore, the optimal treatment for pregnancies complicated with TTTTS is still controversial.

The effect of chorionicity and twin-to-twin delivery time interval on short-term outcome of the second twin

DEFF Research Database (Denmark)

Hjortø, Sofie; Nickelsen, Carsten; Petersen, Janne

2013-01-01

Abstract Objectives: To investigate the effect of chorionicity and twin-to-twin delivery time interval on short-term outcome in the second twin. Additionally, to investigate predictors of adverse outcome in both twins. Methods: Data included vaginally delivered twins (≥ 36 weeks) from Copenhagen ...

Genome-wide association analysis identifies 11 risk variants associated with the asthma with hay fever phenotype.

Science.gov (United States)

Ferreira, Manuel A R; Matheson, Melanie C; Tang, Clara S; Granell, Raquel; Ang, Wei; Hui, Jennie; Kiefer, Amy K; Duffy, David L; Baltic, Svetlana; Danoy, Patrick; Bui, Minh; Price, Loren; Sly, Peter D; Eriksson, Nicholas; Madden, Pamela A; Abramson, Michael J; Holt, Patrick G; Heath, Andrew C; Hunter, Michael; Musk, Bill; Robertson, Colin F; Le Souëf, Peter; Montgomery, Grant W; Henderson, A John; Tung, Joyce Y; Dharmage, Shyamali C; Brown, Matthew A; James, Alan; Thompson, Philip J; Pennell, Craig; Martin, Nicholas G; Evans, David M; Hinds, David A; Hopper, John L

2014-06-01

To date, no genome-wide association study (GWAS) has considered the combined phenotype of asthma with hay fever. Previous analyses of family data from the Tasmanian Longitudinal Health Study provide evidence that this phenotype has a stronger genetic cause than asthma without hay fever. We sought to perform a GWAS of asthma with hay fever to identify variants associated with having both diseases. We performed a meta-analysis of GWASs comparing persons with both physician-diagnosed asthma and hay fever (n = 6,685) with persons with neither disease (n = 14,091). At genome-wide significance, we identified 11 independent variants associated with the risk of having asthma with hay fever, including 2 associations reaching this level of significance with allergic disease for the first time: ZBTB10 (rs7009110; odds ratio [OR], 1.14; P = 4 × 10(-9)) and CLEC16A (rs62026376; OR, 1.17; P = 1 × 10(-8)). The rs62026376:C allele associated with increased asthma with hay fever risk has been found to be associated also with decreased expression of the nearby DEXI gene in monocytes. The 11 variants were associated with the risk of asthma and hay fever separately, but the estimated associations with the individual phenotypes were weaker than with the combined asthma with hay fever phenotype. A variant near LRRC32 was a stronger risk factor for hay fever than for asthma, whereas the reverse was observed for variants in/near GSDMA and TSLP. Single nucleotide polymorphisms with suggestive evidence for association with asthma with hay fever risk included rs41295115 near IL2RA (OR, 1.28; P = 5 × 10(-7)) and rs76043829 in TNS1 (OR, 1.23; P = 2 × 10(-6)). By focusing on the combined phenotype of asthma with hay fever, variants associated with the risk of allergic disease can be identified with greater efficiency. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Crystal substructures of the rotation-twinned T (Al20Cu2Mn3) phase in 2024 aluminum alloy

International Nuclear Information System (INIS)

Feng, Z.Q.; Yang, Y.Q.; Huang, B.; Li, M.H.; Chen, Y.X.; Ru, J.G.

2014-01-01

Highlights: • The substructures in rotation-twinned T (Al 20 Cu 2 Mn 3 ) particles were investigated. • A flattened hexagonal structural subunit with 20 atomic columns was proposed. • The stacking mode of these subunits at APB and TB were revealed. • The transition structures at twin domain junctions were unraveled. -- Abstract: The substructures in rotation-twinned T (Al 20 Cu 2 Mn 3 ) particles were investigated by means of high resolution transmission electron microscopy (HRTEM) and high angle annular dark field scanning transmission electron microscopy (HAADF-STEM) in the present work. A flattened hexagonal structural subunit with 20 atomic columns was proposed. The stacking mode of these subunits in non-defective T phase was proved to be tessellation of many flattened hexagonal subunits with the same orientations, while the stacking modes near anti-phase boundary (APB) and twin boundary (TB) were tessellations of two differently oriented flattened hexagonal subunits. The transition region at twin domain junctions has hybrid structure and perfect or imperfect pentagram structure. Centered with the perfect pentagram transition structure, a rotation twin with ten fan-shaped domains and constituted by five twin variants can be deduced

Twin Research and the Arts: Interconnections / Twin Research: Twin Studies of Sexual Orientation; A Historical Biological Twin Gem; GWAS Approach to Who Has Twins / Newsworthy: Twins on College Campuses; 'Brainprint': Personal Identification by Brain Waves.

Science.gov (United States)

Segal, Nancy L

2016-08-01

The interrelatedness between twin research and the arts is explored via a new play about a famous case. In the 1960s, identical twin David Bruce Reimer was accidentally castrated as an infant during circumcision to correct a urinary problem. The decision to raise him as a girl, and the consequences of that decision, are explored in the new theatrical production of Boy. Other examples of the arts mirroring science, and vice versa, are described. Next, brief reviews and summaries of twin research on sexual orientation, 1860s' knowledge of placental arrangements and twinning mechanisms, and genes underlying multiple birth conception and fertility related measures are provided. This article concludes with a look at twins on college campuses and the identification of individuals by their brain waves. A correction and clarification regarding my article on the Brazilian Twin Registry in the last issue of THG (Segal, 2016) is also provided.

Buoyant Helical Twin-Axial Wire Antenna

Science.gov (United States)

2016-11-15

February 2017 The below identified patent application is available for licensing. Requests for information should be addressed to...300169 1 of 9 BUOYANT HELICAL TWIN-AXIAL WIRE ANTENNA CROSS REFERENCE TO OTHER PATENT APPLICATIONS [0001] This application is a divisional...application and claims the benefit of the filing date of United States Patent Application No. 14/280,889; filed on May 19, 2014; and entitled “Twin-Axial

Prevalence of mutations and functional analyses of melanocortin 4 receptor variants identified among 750 men with juvenile-onset obesity

DEFF Research Database (Denmark)

Larsen, Lesli H; Echwald, Søren Morgenthaler; Sørensen, Thorkild I A

2005-01-01

)) for mutations in MC4R. A total of 14 different mutations were identified of which two, Ala219Val and Leu325Phe, were novel variants. The variant receptor, Leu325Phe, was unable to bind [Nle4,d-Phe7]-alphaMSH, whereas the Ala219Val variant showed a significantly impaired melanotan II induction of cAMP, compared...

Conjoined twins – role of imaging and recent advances

Directory of Open Access Journals (Sweden)

Rishi Philip Mathew

2017-12-01

Full Text Available Introduction: Conjoined twins are identical twins with fused bodies, joined in utero. They are rare complications of monochorionic twinning. The purpose of this study is to describe the various types of conjoined twins, the role of imaging and recent advances aiding in their management. Material and methods: This was a twin institutional study involving 3 cases of conjoined twins diagnosed over a period of 6 years from 2010 to 2015. All the 3 cases were identified antenatally by ultrasound. Only one case was further evaluated by MRI. Results: Three cases of conjoined twins (cephalopagus, thoracopagus and omphalopagus were accurately diagnosed on antenatal ultrasound. After detailed counseling of the parents and obtaining written consent, all the three cases of pregnancy were terminated. Delivery of the viable conjoined twins was achieved without any complications to the mothers, and all the three conjoined twins died after a few minutes. Conclusion: Ultrasound enables an early and accurate diagnosis of conjoined twins, which is vital for obstetric management. MRI is reserved for better tissue characterization. Termination of pregnancy when opted, should be done at an early stage as later stages are fraught with problems. Recent advances, such as 3D printing, may aid in surgical pre-planning, thereby enabling successful surgical separation of conjoined twins.

Interactions between coherent twin boundaries and phase transition of iron under dynamic loading and unloading

Science.gov (United States)

Wang, Kun; Chen, Jun; Zhang, Xueyang; Zhu, Wenjun

2017-09-01

Phase transitions and deformation twins are constantly reported in many BCC metals under high pressure, whose interactions are of fundamental importance to understand the strengthening mechanism of these metals under extreme conditions. However, the interactions between twins and phase transition in BCC metals remain largely unexplored. In this work, interactions between coherent twin boundaries and α ↔ ɛ phase transition of iron are investigated using both non-equilibrium molecular dynamics simulations and the nudged elastic band method. Mechanisms of both twin-assisted phase transition and reverse phase transition are studied, and orientation relationships between BCC and HCP phases are found to be ⟨"separators="|11 1 ¯ ⟩ B C C||⟨"separators="|1 ¯2 1 ¯ 0 ⟩ H C P and ⟨"separators="|1 1 ¯ 0 ⟩ B C C||⟨"separators="|0001 ⟩ H C P for both cases. The twin boundary corresponds to {"separators="|10 1 ¯ 0 } H C P after the phase transition. It is amazing that the reverse transition seems to be able to "memorize" and recover the initial BCC twins. The memory would be partly lost when plastic slips take place in the HCP phase before the reverse transition. In the recovered initial BCC twins, three major twin spacings are observed, which are well explained in terms of energy barriers of transition from the HCP phase to the BCC twin. Besides, the variant selection rule of the twin assisted phase transition is also discussed. The results of present work could be expected to give some clues for producing ultra-fine grain structures in materials exhibiting martensitic phase transition.

On the deformation twinning of Mg AZ31B

DEFF Research Database (Denmark)

Abdolvand, Hamidreza; Majkut, Marta; Oddershede, Jette

2015-01-01

and grain volumes are used to construct various 3D microstructures and model them with a Crystal Plasticity Finite Element (CPFE) code. It is observed that the average grain-resolved stress did not always select the highest ranked Schmid factor twin variant. In fact, the contribution of lower ranked......Crystals with a hexagonal close-packed (HCP) structure are inherently anisotropic, and have a limited number of independent slip systems, which leads to strong deformation textures and reduced formability in polycrystalline products. Tension along the c-axis of the crystal ideally activates......-ray diffraction (3DXRD) was used to map the center-of-mass positions, volumes, orientations, elastic strains, and stress tensors of over 1400 grains in-situ up to a true strain of 1.4%. More than 700 tensile twins were observed to form in the mapped volume under deformation. The measured center-of-mass positions...

Genomewide association study identifies no major founder variant in ...

Indian Academy of Sciences (India)

2013-12-10

Dec 10, 2013 ... variant in Caucasian moyamoya disease ... 1Department of Health and Environmental Sciences, Kyoto University Graduate ... a low prevalence in European countries (Goto and Yonekawa. 1992; Kuroda and Houkin 2008). We have found that the p.R4810K variant in the ring finger protein 213 (RNF213).

Intragranular twinning, detwinning, and twinning-like lattice reorientation in magnesium alloys

International Nuclear Information System (INIS)

Wu, Wei; Gao, Yanfei; Li, Nan; Parish, Chad M.; Liu, Wenjun; Liaw, Peter K.; An, Ke

2016-01-01

Deformation twinning plays a critical role on improving metals or alloys ductility, especially for hexagonal close-packed materials with low symmetry crystal structure. A rolled Mg alloy was selected as a model system to investigate the extension twinning behaviors and characteristics of parent-twin interactions by nondestructive in situ 3D synchrotron X-ray microbeam diffraction. Besides twinning-detwinning process, the “twinning-like” lattice reorientation process was captured within an individual grain inside a bulk material during the strain reversal. The distributions of parent, twin, and reorientated grains and sub-micron level strain variation across the twin boundary are revealed. A theoretical calculation of the lattice strain confirms that the internal strain distribution in parent and twinned grains correlates with the experimental setup, grain orientation of parent, twin, and surrounding grains, as well as the strain path changes. The study suggests a novel deformation mechanism within the hexagonal close-packed structure that cannot be determined from surface-based characterization methods.

Clinical Factors Associated With Presentation Change of the Second Twin After Vaginal Delivery of the First Twin.

Science.gov (United States)

Panelli, Danielle M; Easter, Sarah Rae; Bibbo, Carolina; Robinson, Julian N; Carusi, Daniela A

2017-11-01

To identify clinical factors associated with a change from vertex to nonvertex presentation in the second twin after vaginal birth of the first. We assembled a retrospective cohort of women with viable vertex-vertex twin pregnancies who delivered the presenting twin vaginally. Women whose second twin changed from vertex to nonvertex after vaginal birth of the first were classified as experiencing an intrapartum change in presentation. Characteristics associated with intrapartum presentation change in a univariate analysis with a P value ≤.10 were then evaluated in a multivariate logistic regression model. Four-hundred fifty women met inclusion criteria, of whom 55 (12%) had intrapartum presentation change of the second twin. Women experiencing intrapartum presentation change were more likely to be multiparous (69% compared with 47%, Ppresentation of the second twin between the most recent antepartum ultrasonogram and the ultrasonogram done on admission to labor and delivery (11% compared with 4%, P=.04). In an adjusted analysis, multiparity and gestational age less than 34 weeks were significantly associated with presentation change (adjusted odds ratio [OR] 2.9, 95% CI 1.5-5.6 and adjusted OR 2.6, 95% CI 1.1-5.9, respectively). Women with intrapartum presentation change were more likely to undergo cesarean delivery for their second twin (44% compared with 7%, Ppresentation. Twenty of the 24 (83%) cesarean deliveries performed in the intrapartum presentation change group were done for issues related to malpresentation. Multiparity and gestational age less than 34 weeks are associated with intrapartum presentation change of the second twin.

Genetic variants associated with subjective well-being, depressive symptoms and neuroticism identified through genome-wide analyses

Science.gov (United States)

Derringer, Jaime; Gratten, Jacob; Lee, James J; Liu, Jimmy Z; de Vlaming, Ronald; Ahluwalia, Tarunveer S; Buchwald, Jadwiga; Cavadino, Alana; Frazier-Wood, Alexis C; Davies, Gail; Furlotte, Nicholas A; Garfield, Victoria; Geisel, Marie Henrike; Gonzalez, Juan R; Haitjema, Saskia; Karlsson, Robert; van der Laan, Sander W; Ladwig, Karl-Heinz; Lahti, Jari; van der Lee, Sven J; Miller, Michael B; Lind, Penelope A; Liu, Tian; Matteson, Lindsay; Mihailov, Evelin; Minica, Camelia C; Nolte, Ilja M; Mook-Kanamori, Dennis O; van der Most, Peter J; Oldmeadow, Christopher; Qian, Yong; Raitakari, Olli; Rawal, Rajesh; Realo, Anu; Rueedi, Rico; Schmidt, Börge; Smith, Albert V; Stergiakouli, Evie; Tanaka, Toshiko; Taylor, Kent; Thorleifsson, Gudmar; Wedenoja, Juho; Wellmann, Juergen; Westra, Harm-Jan; Willems, Sara M; Zhao, Wei; Amin, Najaf; Bakshi, Andrew; Bergmann, Sven; Bjornsdottir, Gyda; Boyle, Patricia A; Cherney, Samantha; Cox, Simon R; Davis, Oliver S P; Ding, Jun; Direk, Nese; Eibich, Peter; Emeny, Rebecca T; Fatemifar, Ghazaleh; Faul, Jessica D; Ferrucci, Luigi; Forstner, Andreas J; Gieger, Christian; Gupta, Richa; Harris, Tamara B; Harris, Juliette M; Holliday, Elizabeth G; Hottenga, Jouke-Jan; De Jager, Philip L; Kaakinen, Marika A; Kajantie, Eero; Karhunen, Ville; Kolcic, Ivana; Kumari, Meena; Launer, Lenore J; Franke, Lude; Li-Gao, Ruifang; Liewald, David C; Koini, Marisa; Loukola, Anu; Marques-Vidal, Pedro; Montgomery, Grant W; Mosing, Miriam A; Paternoster, Lavinia; Pattie, Alison; Petrovic, Katja E; Pulkki-Råback, Laura; Quaye, Lydia; Räikkönen, Katri; Rudan, Igor; Scott, Rodney J; Smith, Jennifer A; Sutin, Angelina R; Trzaskowski, Maciej; Vinkhuyzen, Anna E; Yu, Lei; Zabaneh, Delilah; Attia, John R; Bennett, David A; Berger, Klaus; Bertram, Lars; Boomsma, Dorret I; Snieder, Harold; Chang, Shun-Chiao; Cucca, Francesco; Deary, Ian J; van Duijn, Cornelia M; Eriksson, Johan G; Bültmann, Ute; de Geus, Eco J C; Groenen, Patrick J F; Gudnason, Vilmundur; Hansen, Torben; Hartman, Catharine A; Haworth, Claire M A; Hayward, Caroline; Heath, Andrew C; Hinds, David A; Hyppönen, Elina; Iacono, William G; Järvelin, Marjo-Riitta; Jöckel, Karl-Heinz; Kaprio, Jaakko; Kardia, Sharon L R; Keltikangas-Järvinen, Liisa; Kraft, Peter; Kubzansky, Laura D; Lehtimäki, Terho; Magnusson, Patrik K E; Martin, Nicholas G; McGue, Matt; Metspalu, Andres; Mills, Melinda; de Mutsert, Renée; Oldehinkel, Albertine J; Pasterkamp, Gerard; Pedersen, Nancy L; Plomin, Robert; Polasek, Ozren; Power, Christine; Rich, Stephen S; Rosendaal, Frits R; den Ruijter, Hester M; Schlessinger, David; Schmidt, Helena; Svento, Rauli; Schmidt, Reinhold; Alizadeh, Behrooz Z; Sørensen, Thorkild I A; Spector, Tim D; Starr, John M; Stefansson, Kari; Steptoe, Andrew; Terracciano, Antonio; Thorsteinsdottir, Unnur; Thurik, A Roy; Timpson, Nicholas J; Tiemeier, Henning; Uitterlinden, André G; Vollenweider, Peter; Wagner, Gert G; Weir, David R; Yang, Jian; Conley, Dalton C; Smith, George Davey; Hofman, Albert; Johannesson, Magnus; Laibson, David I; Medland, Sarah E; Meyer, Michelle N; Pickrell, Joseph K; Esko, Tõnu; Krueger, Robert F; Beauchamp, Jonathan P; Koellinger, Philipp D; Benjamin, Daniel J; Bartels, Meike; Cesarini, David

2016-01-01

We conducted genome-wide association studies of three phenotypes: subjective well-being (N = 298,420), depressive symptoms (N = 161,460), and neuroticism (N = 170,910). We identified three variants associated with subjective well-being, two with depressive symptoms, and eleven with neuroticism, including two inversion polymorphisms. The two depressive symptoms loci replicate in an independent depression sample. Joint analyses that exploit the high genetic correlations between the phenotypes (|ρ^| ≈ 0.8) strengthen the overall credibility of the findings, and allow us to identify additional variants. Across our phenotypes, loci regulating expression in central nervous system and adrenal/pancreas tissues are strongly enriched for association. PMID:27089181

Association of Caucasian-identified variants with colorectal cancer risk in Singapore Chinese.

Directory of Open Access Journals (Sweden)

Lai Fun Thean

Full Text Available Genome-wide association studies (GWAS in Caucasians have identified fourteen index single nucleotide polymorphisms (iSNPs that influence colorectal cancer (CRC risk.We investigated the role of eleven iSNPs or surrogate SNPs (sSNPs, in high linkage disequilibrium (LD, r(2≥ 0.8 and within 100 kb vicinity of iSNPs, in 2,000 age- and gender-matched Singapore Chinese (SCH cases and controls.Only iSNP rs6983267 at 8q24.21 and sSNPs rs6695584, rs11986063, rs3087967, rs2059254, and rs7226855 at 1q41, 8q23.3, 11q23.1, 16q22.1 and 18q21.1 respectively showed evidence of association with CRC risk, with odds ratios (OR ranging from 1.13 to 1.40. sSNP rs827401 at 10p14 was associated with rectal cancer risk (OR = 0.74, 95% CI 0.63-0.88 but not disease prognosis (OR = 0.91, 95% CI 0.69-1.20. Interestingly, sSNP rs3087967 at 11q23.1 was associated with CRC risk in men (OR = 1.34, 95% CI 1.14-1.58 but not women (OR = 1.07, 95% CI: 0.88-1.29, suggesting a gender-specific role. Half of the Caucasian-identified variants, including the recently fine-mapped BMP pathway loci, BMP4, GREM1, BMP2 and LAMA 5, did not show any evidence for association with CRC in SCH (OR ~1; p-value >0.1. Comparing the results of this study with that of the Northern and Hong Kong Chinese, only variants at chromosomes 8q24.21, 10p14, 11q23.1 and 18q21.1 were replicated in at least two out of the three Chinese studies.The contrasting results between Caucasians and Chinese could be due to different LD patterns and allelic frequencies or genetic heterogeneity. The results suggest that additional common variants contributing to CRC predisposition remained to be identified.

Candidate gene resequencing to identify rare, pedigree-specific variants influencing healthy aging phenotypes in the long life family study

DEFF Research Database (Denmark)

Druley, Todd E; Wang, Lihua; Lin, Shiow J

2016-01-01

from six pedigrees. OBFC1 (chromosome 10) is involved in telomere maintenance, and falls within a linkage peak recently reported from an analysis of telomere length in LLFS families. Two different algorithms for single gene associations identified three genes with an enrichment of variation......BACKGROUND: The Long Life Family Study (LLFS) is an international study to identify the genetic components of various healthy aging phenotypes. We hypothesized that pedigree-specific rare variants at longevity-associated genes could have a similar functional impact on healthy phenotypes. METHODS......: We performed custom hybridization capture sequencing to identify the functional variants in 464 candidate genes for longevity or the major diseases of aging in 615 pedigrees (4,953 individuals) from the LLFS, using a multiplexed, custom hybridization capture. Variants were analyzed individually...

Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses

OpenAIRE

Okbay, Aysu; Baselmans, B.M.L. (Bart M.L.); Neve, Jan-Emmanuel; Turley, Patrick; Nivard, Michel; Fontana, M.A. (Mark Alan); Meddens, S.F.W. (S. Fleur W.); Linnér, R.K. (Richard Karlsson); Rietveld, C.A. (Cornelius A); Derringer, J.; Gratten, Jacob; Lee, James J.; Liu, J.Z. (Jimmy Z); Vlaming, Ronald; SAhluwalia, T. (Tarunveer)

2016-01-01

textabstractVery few genetic variants have been associated with depression and neuroticism, likely because of limitations on sample size in previous studies. Subjective well-being, a phenotype that is genetically correlated with both of these traits, has not yet been studied with genome-wide data. We conducted genome-wide association studies of three phenotypes: subjective well-being (n = 298,420), depressive symptoms (n = 161,460), and neuroticism (n = 170,911). We identify 3 variants associ...

Simulations of stress-induced twinning and de-twinning: A phase field model

International Nuclear Information System (INIS)

Hu Shenyang; Henager, Chuck H.; Chen Longqing

2010-01-01

Twinning in certain metals or under certain conditions is a major plastic deformation mode. Here we present a phase field model to describe twin formation and evolution in a polycrystalline fcc metal under loading and unloading. The model assumes that twin nucleation, growth and de-twinning is a process of partial dislocation nucleation and slip on successive habit planes. Stacking fault energies, energy pathways (γ surfaces), critical shear stresses for the formation of stacking faults and dislocation core energies are used to construct the thermodynamic model. The simulation results demonstrate that the model is able to predict the nucleation of twins and partial dislocations, as well as the morphology of the twin nuclei, and to reasonably describe twin growth and interaction. The twin microstructures at grain boundaries are in agreement with experimental observation. It was found that de-twinning occurs during unloading in the simulations, however, a strong dependence of twin structure evolution on loading history was observed.

Twins and Kindergarten Separation: Divergent Beliefs of Principals, Teachers, Parents, and Twins

Science.gov (United States)

Gordon, Lynn Melby

2015-01-01

Should principals enforce mandatory separation of twins in kindergarten? Do school separation beliefs of principals differ from those of teachers, parents of twins, and twins themselves? This survey questioned 131 elementary principals, 54 kindergarten teachers, 201 parents of twins, and 112 twins. A majority of principals (71%) believed that…

Association between the birth of twins and parental divorce.

Science.gov (United States)

Jena, Anupam B; Goldman, Dana P; Joyce, Geoffrey

2011-04-01

Mothers of multiple births face higher rates of postpartum depression, yet evidence on the marital consequences of multiple births is limited. We examined the association between twin births and parental divorce. We used the 1980 U.S. Census to identify a large sample of mothers with and without twin births. The goal was to estimate multivariate logistic models of the association between birth of twins and divorce adjusting for race, age at marriage and first birth, and college education. We examined whether the association was affected by maternal education, age and sex composition of twins, and family size. Twins at first birth were associated with greater parental divorce compared with singletons (odds ratio, 1.08; 95% confidence interval, 1.01-1.16; absolute risk 13.7% with twins compared with 12.7%; P=.02). The association was statistically greater among mothers not attending college (14.9% with twins compared with 13.3%; P=.01) compared with those with some college (10.4% with twins compared with 10.5%; P=.34); those with children older than 8 years (15.6% with twins compared with 13.5%; P<.01) compared with younger children (10.6% with twins compared with 10.8%; P=.42); and those with at least one twin girl (13.8% with twins compared with 12.6%; P=.03) compared with twin boys (12.1% with twins compared with 12.5%, P=.38). Mothers with four or more children had a larger association between birth of twins and divorce (15.4% for mothers with twins at fourth birth compared with 11.3% for all other mothers with four or more children; P<.01) compared with mothers with twins at first birth (13.7% for twins at first birth compared with 12.7%; P=.02). Health consequences of twin births for children and mothers are well known. Twin births may be associated with longer-term parental divorce. Specific groups, namely mothers not completing college and mothers who already have more children, may be at higher risk. II.

Twin-twin transfusion syndrome: etiology, severity and rational management

NARCIS (Netherlands)

van Gemert, M. J.; Umur, A.; Tijssen, J. G.; Ross, M. G.

2001-01-01

The twin-twin transfusion syndrome is a serious complication of monochorionic twin pregnancies. Partly as a result of an inadequate understanding of the pathophysiology of the syndrome, there is a lack of consensus in clinical management. We sought to review the available information on the etiology

Whole-exome sequencing identifies rare and low-frequency coding variants associated with LDL cholesterol

NARCIS (Netherlands)

L.A. Lange (Leslie); Y. Hu (Youna); H. Zhang (He); C. Xue (Chenyi); E.M. Schmidt (Ellen); Z.-Z. Tang (Zheng-Zheng); C. Bizon (Chris); E.M. Lange (Ethan); G.D. Smith; E.H. Turner (Emily); Y. Jun (Yang); H.M. Kang (Hyun Min); G.M. Peloso (Gina); P. Auer (Paul); K.-P. Li (Kuo-Ping); J. Flannick (Jason); J. Zhang (Ji); C. Fuchsberger (Christian); K. Gaulton (Kyle); C.M. Lindgren (Cecilia); A. Locke (Adam); A.K. Manning (Alisa); X. Sim (Xueling); M.A. Rivas (Manuel); O.L. Holmen (Oddgeir); R.F. Gottesman (Rebecca); Y. Lu (Yingchang); D. Ruderfer (Douglas); E.A. Stahl (Eli); Q. Duan (Qing); Y. Li (Yun); P. Durda (Peter); S. Jiao (Shuo); A.J. Isaacs (Aaron); A. Hofman (Albert); J.C. Bis (Joshua); D.D. Correa; M.D. Griswold (Michael); M. Jakobsdottir (Margret); G.D. Smith; P.J. Schreiner (Pamela); M.F. Feitosa (Mary Furlan); Q. Zhang (Qunyuan); J.E. Huffman (Jennifer); S. Crosby; C.L. Wassel (Christina); R. Do (Ron); N. Franceschini (Nora); L.W. Martin (Lisa); J.G. Robinson (Jennifer); T.L. Assimes (Themistocles); D.R. Crosslin (David); E.A. Rosenthal (Elisabeth); M.Y. Tsai (Michael); M. Rieder (Mark); D.N. Farlow (Deborah); A.R. Folsom (Aaron); T. Lumley (Thomas); E.R. Fox (Ervin); C.S. Carlson (Christopher); U. Peters (Ulrike); R.D. Jackson (Rebecca); C.M. van Duijn (Cornelia); A.G. Uitterlinden (André); D. Levy (Daniel); J.I. Rotter (Jerome); H.A. Taylor (Herman); V. Gudnason (Vilmundur); D.S. Siscovick (David); M. Fornage (Myriam); I.B. Borecki (Ingrid); C. Hayward (Caroline); I. Rudan (Igor); Y.E. Chen (Y. Eugene); E.P. Bottinger (Erwin); R.J.F. Loos (Ruth); P. Sætrom (Pål); K. Hveem (Kristian); M. Boehnke (Michael); L. Groop (Leif); M.I. McCarthy (Mark); T. Meitinger (Thomas); C. Ballantyne (Christie); S.B. Gabriel (Stacey); C.J. O'Donnell (Christopher); W.S. Post (Wendy S.); K.E. North (Kari); A. Reiner (Alexander); E.A. Boerwinkle (Eric); B.M. Psaty (Bruce); D. Altshuler (David); S. Kathiresan (Sekar); D.Y. Lin (Dan); G.P. Jarvik (Gail); L.A. Cupples (Adrienne); C. Kooperberg (Charles); J.G. Wilson (James); D.A. Nickerson (Deborah); G.R. Abecasis (Gonçalo); S.S. Rich (Stephen); R.P. Tracy (Russell); C.J. Willer (Cristen)

2014-01-01

textabstractElevated low-density lipoprotein cholesterol (LDL-C) is a treatable, heritable risk factor for cardiovascular disease. Genome-wide association studies (GWASs) have identified 157 variants associated with lipid levels but are not well suited to assess the impact of rare and low-frequency

Altered endoribonuclease activity of apurinic/apyrimidinic endonuclease 1 variants identified in the human population.

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Wan Cheol Kim

Full Text Available Apurinic/apyrimidinic endonuclease 1 (APE1 is the major mammalian enzyme in the DNA base excision repair pathway and cleaves the DNA phosphodiester backbone immediately 5' to abasic sites. APE1 also has 3'-5' DNA exonuclease and 3' DNA phosphodiesterase activities, and regulates transcription factor DNA binding through its redox regulatory function. The human APE1 has recently been shown to endonucleolytically cleave single-stranded regions of RNA. Towards understanding the biological significance of the endoribonuclease activity of APE1, we examined eight different amino acid substitution variants of APE1 previously identified in the human population. Our study shows that six APE1 variants, D148E, Q51H, I64V, G241R, R237A, and G306A, exhibit a 76-85% reduction in endoribonuclease activity against a specific coding region of the c-myc RNA, yet fully retain the ability to cleave apurinic/apyrimidinic DNA. We found that two APE1 variants, L104R and E126D, exhibit a unique RNase inhibitor-resistant endoribonuclease activity, where the proteins cleave c-myc RNA 3' of specific single-stranded guanosine residues. Expression of L104R and E126D APE1 variants in bacterial Origami cells leads to a 60-80% reduction in colony formation and a 1.5-fold increase in cell doubling time, whereas the other variants, which exhibit diminished endoribonuclease activity, had no effect. These data indicate that two human APE1 variants exhibit a unique endoribonuclease activity, which correlates with their ability to induce cytotoxicity or slow down growth in bacterial cells and supports the notion of their biological functionality.

BISQUE: locus- and variant-specific conversion of genomic, transcriptomic and proteomic database identifiers.

Science.gov (United States)

Meyer, Michael J; Geske, Philip; Yu, Haiyuan

2016-05-15

Biological sequence databases are integral to efforts to characterize and understand biological molecules and share biological data. However, when analyzing these data, scientists are often left holding disparate biological currency-molecular identifiers from different databases. For downstream applications that require converting the identifiers themselves, there are many resources available, but analyzing associated loci and variants can be cumbersome if data is not given in a form amenable to particular analyses. Here we present BISQUE, a web server and customizable command-line tool for converting molecular identifiers and their contained loci and variants between different database conventions. BISQUE uses a graph traversal algorithm to generalize the conversion process for residues in the human genome, genes, transcripts and proteins, allowing for conversion across classes of molecules and in all directions through an intuitive web interface and a URL-based web service. BISQUE is freely available via the web using any major web browser (http://bisque.yulab.org/). Source code is available in a public GitHub repository (https://github.com/hyulab/BISQUE). haiyuan.yu@cornell.edu Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Candidate gene linkage approach to identify DNA variants that predispose to preterm birth

DEFF Research Database (Denmark)

Bream, Elise N A; Leppellere, Cara R; Cooper, Margaret E

2013-01-01

Background:The aim of this study was to identify genetic variants contributing to preterm birth (PTB) using a linkage candidate gene approach.Methods:We studied 99 single-nucleotide polymorphisms (SNPs) for 33 genes in 257 families with PTBs segregating. Nonparametric and parametric analyses were...... through the infant and/or the mother in the etiology of PTB....

The mobility of growth twins synthesized by sputtering: Tailoring the twin thickness

International Nuclear Information System (INIS)

Velasco, Leonardo; Hodge, Andrea M.

2016-01-01

The current work presents a protean twin thickness contour zone map that illustrates how the nucleation and the mobility of twin boundaries affects the twin thickness of sputtered films. The twin thickness contour zone map can be used as a versatile guide to synthesize fully nanotwinned films with tailored twin thicknesses in materials with a wide range of stacking fault energies. The nucleation and mobility of twin boundaries was studied in four Cu alloys of different compositions (Cu-6wt.%Al, Cu-4wt.%Al, Cu-2wt.%Al, and Cu-10wt.%Ni), having stacking fault energies ranging from 6 mJ/m 2 to 60 mJ/m 2 . The films were synthesized by magnetron sputtering and characterized by transmission electron microscopy, where the twin thickness varied from 2 nm to 35 nm. Our experimental results show that it is possible to control the twin thickness. Three main mechanisms are explained to describe twin nucleation and twin boundary mobility, which are correlated to the interplay of specific sputtering conditions and the deposition temperature.

Quality of life in unaffected twins discordant for affective disorder

DEFF Research Database (Denmark)

Vinberg, Maj; Bech, Per; Kyvik, Kirsten Ohm

2006-01-01

BACKGROUND: The disability and hardship associated with affective disorder is shared by the family members of affective patients and might affect the family member's quality of life. METHOD: In a cross-sectional, high-risk, case-control study, monozygotic (MZ) and dizygotic (DZ) twins with (High......-Risk twins) and without (the control group/Low-Risk twins) a co-twin history of affective disorder were identified through nationwide registers. The aim of the present study was to investigate the hypothesis that a genetic liability to affective disorder is associated with a lower perception of quality...

The Qingdao Twin Registry

DEFF Research Database (Denmark)

Duan, Haiping; Ning, Feng; Zhang, Dongfeng

2013-01-01

In 1998, the Qingdao Twin Registry was initiated as the main part of the Chinese National Twin Registry. By 2005, a total of 10,655 twin pairs had been recruited. Since then new twin cohorts have been sampled, with one longitudinal cohort of adolescent twins selected to explore determinants of me...

Twins and non-twin siblings: different estimates of shared environmental influence in early childhood.

Science.gov (United States)

Koeppen-Schomerus, Gesina; Spinath, Frank M; Plomin, Robert

2003-04-01

Twin studies typically indicate shared environmental influence for cognitive abilities, especially in early childhood. However, across studies, DZ twin correlations tend to be greater than non-twin sibling correlations, suggesting that twin estimates of shared environment are to some extent specific to twins. We tested this hypothesis in a sample of more than 1800 MZ and 1800 same-sex DZ pairs from the Twins Early Development Study (TEDS), a study of twins born in England and Wales in 1994 and 1995. For this analysis, we obtained comparable data from more than 130 same-sex younger siblings of the twins. Twins and their younger siblings were assessed for language, cognitive abilities and behavior problems by their parents at 2 and 3 years of age. For language and cognitive measures at both 2 and 3 years, but not for behavior problems, estimates of shared environment were more than twice as large for twins as compared to non-twin siblings. We conclude that about half of twin study estimates of shared environment for cognitive abilities in early childhood are specific to twins. Although many possibilities exist for explaining the special shared environment effect for twins, we suggest that cognitive-relevant experiences that are not shared by siblings are shared by twins because they are exactly the same age.

Effect of co-twin gender on neurodevelopmental symptoms: a twin register study.

Science.gov (United States)

Eriksson, Jonna Maria; Lundström, Sebastian; Lichtenstein, Paul; Bejerot, Susanne; Eriksson, Elias

2016-01-01

Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are neurodevelopmental disorders thought to have both genetic and environmental causes. It has been hypothesized that exposure to elevated levels of prenatal testosterone is associated with elevated traits of ASD and ADHD. Assuming that testosterone levels from a dizygotic male twin fetus may lead to enhanced testosterone exposure of its co-twins, we aimed to test the prenatal testosterone hypothesis by comparing same-sex with opposite-sex dizygotic twins with respect to neurodevelopmental symptoms. Neuropsychiatric traits were assessed in a population-based twin cohort from the Child and Adolescent Twin Study in Sweden (CATSS). Parental interviews were conducted for 16,312 dizygotic twins, 9 and 12 years old, with the Autism-Tics, ADHD, and other Comorbidities inventory (A-TAC). Girls with a female co-twin had an increased risk of reaching the cut-off score for ADHD compared with girls with a male co-twin. Both boys and girls with a female co-twin displayed a larger number of traits related to attention deficit and repetitive and stereotyped behaviors than those with a male twin. In girls, this also extended to social interaction and the combined measures for ASD and ADHD, however, with small effect sizes. Our results are reverse to what would have been expected from the prenatal testosterone hypothesis but consistent with a previous study of ASD and ADHD traits in dizygotic twins. The seemingly protective effect for girls of having a twin brother may be an effect of parent report bias, but may also be an unexpected effect of sharing the intrauterine environment with a male co-twin.

Attractiveness Differences Between Twins Predicts Evaluations of Self and Co-Twin

Science.gov (United States)

Principe, Connor P.; Rosen, Lisa H.; Taylor-Partridge, Teresa; Langlois, Judith H.

2012-01-01

One of the most consistent findings in psychology shows that people prefer and make positive attributions about attractive compared with unattractive people. The goal of the current study was to determine the power of attractiveness effects by testing whether these social judgments are made where attractiveness differences are smallest: between twins. Differences in facial attractiveness predicted twins’ evaluations of self and their co-twin (n = 158; 54 male). In twin pairs, the more attractive twin judged their less attractive sibling as less physically attractive, athletic, socially competent, and emotionally stable. The less attractive twin did the reverse. Given that even negligible differences in facial attractiveness predicted self and co-twin attitudes, these results provide the strongest test yet of appearance-based stereotypes. PMID:23467329

Effect of grain size of parent phase on twinning modes of B19` martensite in an equiatomic Ti-Ni shape memory alloy

Energy Technology Data Exchange (ETDEWEB)

Nishida, M. [Kumamoto Univ. (Japan). Dept. of Mater. Sci. and Resource Eng.; Itai, I. [Kumamoto Univ. (Japan). Dept. of Mater. Sci. and Resource Eng.; Kitamura, K. [Kumamoto Univ. (Japan). Dept. of Mater. Sci. and Resource Eng.; Chiba, A. [Kumamoto Univ. (Japan). Dept. of Mater. Sci. and Resource Eng.; Yamauchi, K. [Tokin Corp., Sendai (Japan)

1995-12-01

The effect of grain size of B2 parent phase on the twinning modes of B19` martensite in a Ti-50.0 at% Ni shape memory alloy has been studied. The grain size of parent phase was controlled from submicrons to several ten microns by cold-rolling and subsequent annealing. (001) compound twins were dominantly observed in the grain less than 4 {mu}m in diameter, although the (001) compound twinning did not give a solution to the phenomenological crystallographic theory. The triangular self-accommodating morphology of the martensite variants consisting of left angle 011 right angle Type II twins which were theoretically and experimentally recognized as a lattice invariant shear of the present transformation appeared in the whole grain more than 4 {mu}m in diameter. The formation mechanism of the (001) compound twinning in the fine grain is also discussed. (orig.).

Functional and effective whole brain connectivity using magnetoencephalography to identify monozygotic twin pairs

NARCIS (Netherlands)

Demuru, M.; Gouw, A.; Hillebrand, A.; Stam, C J; van Dijk, B W; Scheltens, P.; Tijms, B.M.; Konijnenberg, E.; ten Kate-Booij, M.J.; den Braber, A; Smit, D J A; Boomsma, D I; Visser, P J

2017-01-01

Resting-state functional connectivity patterns are highly stable over time within subjects. This suggests that such 'functional fingerprints' may have strong genetic component. We investigated whether the functional (FC) or effective (EC) connectivity patterns of one monozygotic twin could be used

Quality of life in unaffected twins discordant for affective disorder

DEFF Research Database (Denmark)

Vinberg, Maj; Bech, Per; Kyvik, Kirsten Ohm

2007-01-01

-Risk twins) and without (the control group/Low-Risk twins) a co-twin history of affective disorder were identified through nationwide registers. The aim of the present study was to investigate the hypothesis that a genetic liability to affective disorder is associated with a lower perception of quality......BACKGROUND: The disability and hardship associated with affective disorder is shared by the family members of affective patients and might affect the family member's quality of life. METHOD: In a cross-sectional, high-risk, case-control study, monozygotic (MZ) and dizygotic (DZ) twins with (High...... of life. RESULTS: Univariate analyses showed that quality of life in all domains was impaired for the 121 High-Risk twins compared to the 84 Low-Risk twins. In multiple regression analyses, the differences remained significant after adjustment for sex, age, marital status and years of education. Adjusted...

Comprehensive genomic analysis identifies pathogenic variants in maturity-onset diabetes of the young (MODY) patients in South India.

Science.gov (United States)

Mohan, Viswanathan; Radha, Venkatesan; Nguyen, Thong T; Stawiski, Eric W; Pahuja, Kanika Bajaj; Goldstein, Leonard D; Tom, Jennifer; Anjana, Ranjit Mohan; Kong-Beltran, Monica; Bhangale, Tushar; Jahnavi, Suresh; Chandni, Radhakrishnan; Gayathri, Vijay; George, Paul; Zhang, Na; Murugan, Sakthivel; Phalke, Sameer; Chaudhuri, Subhra; Gupta, Ravi; Zhang, Jingli; Santhosh, Sam; Stinson, Jeremy; Modrusan, Zora; Ramprasad, V L; Seshagiri, Somasekar; Peterson, Andrew S

2018-02-13

Maturity-onset diabetes of the young (MODY) is an early-onset, autosomal dominant form of non-insulin dependent diabetes. Genetic diagnosis of MODY can transform patient management. Earlier data on the genetic predisposition to MODY have come primarily from familial studies in populations of European origin. In this study, we carried out a comprehensive genomic analysis of 289 individuals from India that included 152 clinically diagnosed MODY cases to identify variants in known MODY genes. Further, we have analyzed exome data to identify putative MODY relevant variants in genes previously not implicated in MODY. Functional validation of MODY relevant variants was also performed. We found MODY 3 (HNF1A; 7.2%) to be most frequently mutated followed by MODY 12 (ABCC8; 3.3%). They together account for ~ 11% of the cases. In addition to known MODY genes, we report the identification of variants in RFX6, WFS1, AKT2, NKX6-1 that may contribute to development of MODY. Functional assessment of the NKX6-1 variants showed that they are functionally impaired. Our findings showed HNF1A and ABCC8 to be the most frequently mutated MODY genes in south India. Further we provide evidence for additional MODY relevant genes, such as NKX6-1, and these require further validation.

The Prenatal Environment in Twin Studies: A Review on Chorionicity

NARCIS (Netherlands)

Marceau, K.; McMaster, M.T.; Smith, T.F.; Daams, J.G.; van Beijsterveldt, C.E.M.; Boomsma, D.I.; Knopik, V.S.

2016-01-01

A literature search was conducted to identify articles examining the association of chorionicity (e.g., whether twins share a single chorion and thus placenta or have separate chorions/placentas) and genetics, psychiatry/behavior, and neurological manifestations in humans twins and higher-order

Monochorionic twin pregnancies

NARCIS (Netherlands)

Hack, K.E.A.

2008-01-01

Following widespread application of assisted reproductive technology modalities and the increased age of motherhood, the incidence of twin gestations has increased markedly. Twins are either monozygotic or dizygotic. Dizygotic (i.e. fraternal) twins result from the fertilization of two different

Two splice variants of the bovine lactoferrin gene identified in Staphylococcus aureus isolated from mastitis in dairy cattle.

Science.gov (United States)

Huang, J M; Wang, Z Y; Ju, Z H; Wang, C F; Li, Q L; Sun, T; Hou, Q L; Hang, S Q; Hou, M H; Zhong, J F

2011-12-21

Bovine lactoferrin (bLF) is a member of the transferrin family; it plays an important role in the innate immune response. We identified novel splice variants of the bLF gene in mastitis-infected and healthy cows. Reverse transcription-polymerase chain reaction (RT-PCR) and clone sequencing analysis were used to screen the splice variants of the bLF gene in the mammary gland, spleen and liver tissues. One main transcript corresponding to the bLF reference sequence was found in three tissues in both healthy and mastitis-infected cows. Quantitative real-time PCR analysis showed that the expression levels of the LF gene's main transcript were not significantly different in tissues from healthy versus mastitis-infected cows. However, the new splice variant, LF-AS2, which has the exon-skipping alternative splicing pattern, was only identified in mammary glands infected with Staphylococcus aureus. Sequencing analysis showed that the new splice variant was 251 bp in length, including exon 1, part of exon 2, part of exon 16, and exon 17. We conclude that bLF may play a role in resistance to mastitis through alternative splicing mechanisms.

Estimating twin concordance for bivariate competing risks twin data

DEFF Research Database (Denmark)

Scheike, Thomas; Holst, Klaus K.; Hjelmborg, Jacob B.

2014-01-01

For twin time-to-event data, we consider different concordance probabilities, such as the casewise concordance that are routinely computed as a measure of the lifetime dependence/correlation for specific diseases. The concordance probability here is the probability that both twins have experience...... events with the competing risk death. We thus aim to quantify the degree of dependence through the casewise concordance function and show a significant genetic component...... the event of interest. Under the assumption that both twins are censored at the same time, we show how to estimate this probability in the presence of right censoring, and as a consequence, we can then estimate the casewise twin concordance. In addition, we can model the magnitude of within pair dependence...... over time, and covariates may be further influential on the marginal risk and dependence structure. We establish the estimators large sample properties and suggest various tests, for example, for inferring familial influence. The method is demonstrated and motivated by specific twin data on cancer...

Single nucleotide variants and InDels identified from whole-genome re-sequencing of Guzerat, Gyr, Girolando and Holstein cattle breeds.

Directory of Open Access Journals (Sweden)

Nedenia Bonvino Stafuzza

Full Text Available Whole-genome re-sequencing, alignment and annotation analyses were undertaken for 12 sires representing four important cattle breeds in Brazil: Guzerat (multi-purpose, Gyr, Girolando and Holstein (dairy production. A total of approximately 4.3 billion reads from an Illumina HiSeq 2000 sequencer generated for each animal 10.7 to 16.4-fold genome coverage. A total of 27,441,279 single nucleotide variations (SNVs and 3,828,041 insertions/deletions (InDels were detected in the samples, of which 2,557,670 SNVs and 883,219 InDels were novel. The submission of these genetic variants to the dbSNP database significantly increased the number of known variants, particularly for the indicine genome. The concordance rate between genotypes obtained using the Bovine HD BeadChip array and the same variants identified by sequencing was about 99.05%. The annotation of variants identified numerous non-synonymous SNVs and frameshift InDels which could affect phenotypic variation. Functional enrichment analysis was performed and revealed that variants in the olfactory transduction pathway was over represented in all four cattle breeds, while the ECM-receptor interaction pathway was over represented in Girolando and Guzerat breeds, the ABC transporters pathway was over represented only in Holstein breed, and the metabolic pathways was over represented only in Gyr breed. The genetic variants discovered here provide a rich resource to help identify potential genomic markers and their associated molecular mechanisms that impact economically important traits for Gyr, Girolando, Guzerat and Holstein breeding programs.

Modeling acardiac twin pregnancies

NARCIS (Netherlands)

de Groot, Rosa; van den Wijngaard, Jeroen P. H. M.; Umur, Asli; Beek, Johan F.; Nikkels, Peter G. J.; van Gemert, Martin J. C.

2007-01-01

Acardiac twin pregnancies are a rare but severe complication of monochorionic twinning, where the acardiac twin lacks cardiac function but nevertheless grows during pregnancy because it is perfused by the pump twin through a set of placental arterioarterial and venovenous anastomoses. Because the

Allele frequencies of variants in ultra conserved elements identify selective pressure on transcription factor binding.

Science.gov (United States)

Silla, Toomas; Kepp, Katrin; Tai, E Shyong; Goh, Liang; Davila, Sonia; Catela Ivkovic, Tina; Calin, George A; Voorhoeve, P Mathijs

2014-01-01

Ultra-conserved genes or elements (UCGs/UCEs) in the human genome are extreme examples of conservation. We characterized natural variations in 2884 UCEs and UCGs in two distinct populations; Singaporean Chinese (n = 280) and Italian (n = 501) by using a pooled sample, targeted capture, sequencing approach. We identify, with high confidence, in these regions the abundance of rare SNVs (MAFpower for association studies. By combining our data with 1000 Genome Project data, we show in three independent datasets that prevalent UCE variants (MAF>5%) are more often found in relatively less-conserved nucleotides within UCEs, compared to rare variants. Moreover, prevalent variants are less likely to overlap transcription factor binding site. Using SNPfold we found no significant influence of RNA secondary structure on UCE conservation. All together, these results suggest UCEs are not under selective pressure as a stretch of DNA but are under differential evolutionary pressure on the single nucleotide level.

The Project TALENT Twin and Sibling Study.

Science.gov (United States)

Prescott, Carol A; Achorn, Deanna Lyter; Kaiser, Ashley; Mitchell, Lindsey; McArdle, John J; Lapham, Susan J

2013-02-01

Project TALENT is a US national longitudinal study of about 377,000 individuals born in 1942-1946, first assessed in 1960. Students in about 1,200 schools participated in a 2-day battery covering aptitudes, abilities, interests, and individual and family characteristics (Flanagan, 1962; www.projectTALENT.org). Follow-up assessments 1, 5, and 11 years later assessed educational and occupational outcomes. The sample includes approximately 92,000 siblings from 40,000 families, including 2,500 twin pairs and 1,200 other siblings of twins. Until recently, almost no behavior genetic research has been conducted with the sample. In the original data collection information was not collected with the intent to link family members. Recently, we developed algorithms using names, addresses, birthdates, and information about family structure to link siblings and identify twins. We are testing several methods to determine zygosity, including use of yearbook photographs. In this paper, we summarize the design and measures in Project TALENT, describe the Twin and Sibling sample, and present our twin-sib-classmate model. In most twin and family designs, the 'shared environment' includes factors specific to the family combined with between-family differences associated with macro-level variables such as socioeconomic status. The school-based sampling design used in Project TALENT provides a unique opportunity to partition the shared environment into variation shared by siblings, specific to twins, and associated with school- and community-level factors. The availability of many measured characteristics on the family, schools, and neighborhoods enhances the ability to study the impact of specific factors on behavioral variation.

Personality and birth order in monozygotic twins adopted apart: a test of Sulloway's theory; Research Reviews: twin births and cancer risk in mothers, male sexual dysfunction, twin study of ultimatum game behavior; Human Interest: 'The Land of Twins', twin-like reunion-I, twin-like reunion-II.

Science.gov (United States)

Segal, Nancy L

2008-02-01

A brief overview of Sulloway's (1996) theory of birth order and personality is presented. A reared apart twin approach for testing his personality findings regarding openness to experience and conscientiousness in first borns and later borns is described. This is followed by summaries of three recent twin studies. The topics include cancer risk in mother of twins, sexual dysfunction in males and responder behavior during ultimatum games. This article concludes with a discussion of twinning rates and rituals among the Yoruba of western Nigeria, and descriptions of two unusual reunions between siblings and twins.

Genetic association study of exfoliation syndrome identifies a protective rare variant at LOXL1 and five new susceptibility loci.

Science.gov (United States)

Aung, Tin; Ozaki, Mineo; Lee, Mei Chin; Schlötzer-Schrehardt, Ursula; Thorleifsson, Gudmar; Mizoguchi, Takanori; Igo, Robert P; Haripriya, Aravind; Williams, Susan E; Astakhov, Yury S; Orr, Andrew C; Burdon, Kathryn P; Nakano, Satoko; Mori, Kazuhiko; Abu-Amero, Khaled; Hauser, Michael; Li, Zheng; Prakadeeswari, Gopalakrishnan; Bailey, Jessica N Cooke; Cherecheanu, Alina Popa; Kang, Jae H; Nelson, Sarah; Hayashi, Ken; Manabe, Shin-Ichi; Kazama, Shigeyasu; Zarnowski, Tomasz; Inoue, Kenji; Irkec, Murat; Coca-Prados, Miguel; Sugiyama, Kazuhisa; Järvelä, Irma; Schlottmann, Patricio; Lerner, S Fabian; Lamari, Hasnaa; Nilgün, Yildirim; Bikbov, Mukharram; Park, Ki Ho; Cha, Soon Cheol; Yamashiro, Kenji; Zenteno, Juan C; Jonas, Jost B; Kumar, Rajesh S; Perera, Shamira A; Chan, Anita S Y; Kobakhidze, Nino; George, Ronnie; Vijaya, Lingam; Do, Tan; Edward, Deepak P; de Juan Marcos, Lourdes; Pakravan, Mohammad; Moghimi, Sasan; Ideta, Ryuichi; Bach-Holm, Daniella; Kappelgaard, Per; Wirostko, Barbara; Thomas, Samuel; Gaston, Daniel; Bedard, Karen; Greer, Wenda L; Yang, Zhenglin; Chen, Xueyi; Huang, Lulin; Sang, Jinghong; Jia, Hongyan; Jia, Liyun; Qiao, Chunyan; Zhang, Hui; Liu, Xuyang; Zhao, Bowen; Wang, Ya-Xing; Xu, Liang; Leruez, Stéphanie; Reynier, Pascal; Chichua, George; Tabagari, Sergo; Uebe, Steffen; Zenkel, Matthias; Berner, Daniel; Mossböck, Georg; Weisschuh, Nicole; Hoja, Ursula; Welge-Luessen, Ulrich-Christoph; Mardin, Christian; Founti, Panayiota; Chatzikyriakidou, Anthi; Pappas, Theofanis; Anastasopoulos, Eleftherios; Lambropoulos, Alexandros; Ghosh, Arkasubhra; Shetty, Rohit; Porporato, Natalia; Saravanan, Vijayan; Venkatesh, Rengaraj; Shivkumar, Chandrashekaran; Kalpana, Narendran; Sarangapani, Sripriya; Kanavi, Mozhgan R; Beni, Afsaneh Naderi; Yazdani, Shahin; Lashay, Alireza; Naderifar, Homa; Khatibi, Nassim; Fea, Antonio; Lavia, Carlo; Dallorto, Laura; Rolle, Teresa; Frezzotti, Paolo; Paoli, Daniela; Salvi, Erika; Manunta, Paolo; Mori, Yosai; Miyata, Kazunori; Higashide, Tomomi; Chihara, Etsuo; Ishiko, Satoshi; Yoshida, Akitoshi; Yanagi, Masahide; Kiuchi, Yoshiaki; Ohashi, Tsutomu; Sakurai, Toshiya; Sugimoto, Takako; Chuman, Hideki; Aihara, Makoto; Inatani, Masaru; Miyake, Masahiro; Gotoh, Norimoto; Matsuda, Fumihiko; Yoshimura, Nagahisa; Ikeda, Yoko; Ueno, Morio; Sotozono, Chie; Jeoung, Jin Wook; Sagong, Min; Park, Kyu Hyung; Ahn, Jeeyun; Cruz-Aguilar, Marisa; Ezzouhairi, Sidi M; Rafei, Abderrahman; Chong, Yaan Fun; Ng, Xiao Yu; Goh, Shuang Ru; Chen, Yueming; Yong, Victor H K; Khan, Muhammad Imran; Olawoye, Olusola O; Ashaye, Adeyinka O; Ugbede, Idakwo; Onakoya, Adeola; Kizor-Akaraiwe, Nkiru; Teekhasaenee, Chaiwat; Suwan, Yanin; Supakontanasan, Wasu; Okeke, Suhanya; Uche, Nkechi J; Asimadu, Ifeoma; Ayub, Humaira; Akhtar, Farah; Kosior-Jarecka, Ewa; Lukasik, Urszula; Lischinsky, Ignacio; Castro, Vania; Grossmann, Rodolfo Perez; Sunaric Megevand, Gordana; Roy, Sylvain; Dervan, Edward; Silke, Eoin; Rao, Aparna; Sahay, Priti; Fornero, Pablo; Cuello, Osvaldo; Sivori, Delia; Zompa, Tamara; Mills, Richard A; Souzeau, Emmanuelle; Mitchell, Paul; Wang, Jie Jin; Hewitt, Alex W; Coote, Michael; Crowston, Jonathan G; Astakhov, Sergei Y; Akopov, Eugeny L; Emelyanov, Anton; Vysochinskaya, Vera; Kazakbaeva, Gyulli; Fayzrakhmanov, Rinat; Al-Obeidan, Saleh A; Owaidhah, Ohoud; Aljasim, Leyla Ali; Chowbay, Balram; Foo, Jia Nee; Soh, Raphael Q; Sim, Kar Seng; Xie, Zhicheng; Cheong, Augustine W O; Mok, Shi Qi; Soo, Hui Meng; Chen, Xiao Yin; Peh, Su Qin; Heng, Khai Koon; Husain, Rahat; Ho, Su-Ling; Hillmer, Axel M; Cheng, Ching-Yu; Escudero-Domínguez, Francisco A; González-Sarmiento, Rogelio; Martinon-Torres, Frederico; Salas, Antonio; Pathanapitoon, Kessara; Hansapinyo, Linda; Wanichwecharugruang, Boonsong; Kitnarong, Naris; Sakuntabhai, Anavaj; Nguyn, Hip X; Nguyn, Giang T T; Nguyn, Trình V; Zenz, Werner; Binder, Alexander; Klobassa, Daniela S; Hibberd, Martin L; Davila, Sonia; Herms, Stefan; Nöthen, Markus M; Moebus, Susanne; Rautenbach, Robyn M; Ziskind, Ari; Carmichael, Trevor R; Ramsay, Michele; Álvarez, Lydia; García, Montserrat; González-Iglesias, Héctor; Rodríguez-Calvo, Pedro P; Fernández-Vega Cueto, Luis; Oguz, Çilingir; Tamcelik, Nevbahar; Atalay, Eray; Batu, Bilge; Aktas, Dilek; Kasım, Burcu; Wilson, M Roy; Coleman, Anne L; Liu, Yutao; Challa, Pratap; Herndon, Leon; Kuchtey, Rachel W; Kuchtey, John; Curtin, Karen; Chaya, Craig J; Crandall, Alan; Zangwill, Linda M; Wong, Tien Yin; Nakano, Masakazu; Kinoshita, Shigeru; den Hollander, Anneke I; Vesti, Eija; Fingert, John H; Lee, Richard K; Sit, Arthur J; Shingleton, Bradford J; Wang, Ningli; Cusi, Daniele; Qamar, Raheel; Kraft, Peter; Pericak-Vance, Margaret A; Raychaudhuri, Soumya; Heegaard, Steffen; Kivelä, Tero; Reis, André; Kruse, Friedrich E; Weinreb, Robert N; Pasquale, Louis R; Haines, Jonathan L; Thorsteinsdottir, Unnur; Jonasson, Fridbert; Allingham, R Rand; Milea, Dan; Ritch, Robert; Kubota, Toshiaki; Tashiro, Kei; Vithana, Eranga N; Micheal, Shazia; Topouzis, Fotis; Craig, Jamie E; Dubina, Michael; Sundaresan, Periasamy; Stefansson, Kari; Wiggs, Janey L; Pasutto, Francesca; Khor, Chiea Chuen

2017-07-01

Exfoliation syndrome (XFS) is the most common known risk factor for secondary glaucoma and a major cause of blindness worldwide. Variants in two genes, LOXL1 and CACNA1A, have previously been associated with XFS. To further elucidate the genetic basis of XFS, we collected a global sample of XFS cases to refine the association at LOXL1, which previously showed inconsistent results across populations, and to identify new variants associated with XFS. We identified a rare protective allele at LOXL1 (p.Phe407, odds ratio (OR) = 25, P = 2.9 × 10 -14 ) through deep resequencing of XFS cases and controls from nine countries. A genome-wide association study (GWAS) of XFS cases and controls from 24 countries followed by replication in 18 countries identified seven genome-wide significant loci (P < 5 × 10 -8 ). We identified association signals at 13q12 (POMP), 11q23.3 (TMEM136), 6p21 (AGPAT1), 3p24 (RBMS3) and 5q23 (near SEMA6A). These findings provide biological insights into the pathology of XFS and highlight a potential role for naturally occurring rare LOXL1 variants in disease biology.

Genome-wide association analysis identifies variants associated with nonalcoholic fatty liver disease that have distinct effects on metabolic traits

DEFF Research Database (Denmark)

Speliotes, Elizabeth K; Yerges-Armstrong, Laura M; Wu, Jun

2011-01-01

steatosis, a non-invasive measure of NAFLD, in large population based samples. Using variance components methods, we show that CT hepatic steatosis is heritable (~26%-27%) in family-based Amish, Family Heart, and Framingham Heart Studies (n¿=¿880 to 3,070). By carrying out a fixed-effects meta......-analysis of genome-wide association (GWA) results between CT hepatic steatosis and ~2.4 million imputed or genotyped SNPs in 7,176 individuals from the Old Order Amish, Age, Gene/Environment Susceptibility-Reykjavik study (AGES), Family Heart, and Framingham Heart Studies, we identify variants associated at genome......Nonalcoholic fatty liver disease (NAFLD) clusters in families, but the only known common genetic variants influencing risk are near PNPLA3. We sought to identify additional genetic variants influencing NAFLD using genome-wide association (GWA) analysis of computed tomography (CT) measured hepatic...

The nature of pseudo-twinning modes on the basis of a twin classification scheme

International Nuclear Information System (INIS)

Singh, Jung B.; Sundararaman, M.; Krishnan, M.

2011-01-01

Pseudo-twins can form in ordered structures under high stress conditions. These twins are defined by lattice sites that are at twin positions but are incorrectly occupied by different species of atoms. The present note discusses if it is possible to further classify pseudo-twins into different modes based on the nature of associated twinning elements.

Computational approaches to identify functional genetic variants in cancer genomes

DEFF Research Database (Denmark)

Gonzalez-Perez, Abel; Mustonen, Ville; Reva, Boris

2013-01-01

The International Cancer Genome Consortium (ICGC) aims to catalog genomic abnormalities in tumors from 50 different cancer types. Genome sequencing reveals hundreds to thousands of somatic mutations in each tumor but only a minority of these drive tumor progression. We present the result of discu......The International Cancer Genome Consortium (ICGC) aims to catalog genomic abnormalities in tumors from 50 different cancer types. Genome sequencing reveals hundreds to thousands of somatic mutations in each tumor but only a minority of these drive tumor progression. We present the result...... of discussions within the ICGC on how to address the challenge of identifying mutations that contribute to oncogenesis, tumor maintenance or response to therapy, and recommend computational techniques to annotate somatic variants and predict their impact on cancer phenotype....

Novel epigenetic changes unveiled by monozygotic twins discordant for smoking habits.

Science.gov (United States)

Allione, Alessandra; Marcon, Francesca; Fiorito, Giovanni; Guarrera, Simonetta; Siniscalchi, Ester; Zijno, Andrea; Crebelli, Riccardo; Matullo, Giuseppe

2015-01-01

Exposure to cigarette smoking affects the epigenome and could increase the risk of developing diseases such as cancer and cardiovascular disorders. Changes in DNA methylation associated with smoking may help to identify molecular pathways that contribute to disease etiology. Previous studies are not completely concordant in the identification of differentially methylated regions in the DNA of smokers. We performed an epigenome-wide DNA methylation study in a group of monozygotic (MZ) twins discordant for smoking habits to determine the effect of smoking on DNA methylation. As MZ twins are considered genetically identical, this model allowed us to identify smoking-related DNA methylation changes independent from genetic components. We investigated the whole blood genome-wide DNA methylation profiles in 20 MZ twin pairs discordant for smoking habits by using the Illumina HumanMethylation450 BeadChip. We identified 22 CpG sites that were differentially methylated between smoker and non-smoker MZ twins by intra-pair analysis. We confirmed eight loci already described by other groups, located in AHRR, F2RL3, MYOG1 genes, at 2q37.1 and 6p21.33 regions, and also identified several new loci. Moreover, pathway analysis showed an enrichment of genes involved in GTPase regulatory activity. Our study confirmed the evidence of smoking-related DNA methylation changes, emphasizing that well-designed MZ twin models can aid the discovery of novel DNA methylation signals, even in a limited sample population.

Whole-exome sequencing identified a variant in EFTUD2 gene in establishing a genetic diagnosis.

Science.gov (United States)

Rengasamy Venugopalan, S; Farrow, E G; Lypka, M

2017-06-01

Craniofacial anomalies are complex and have an overlapping phenotype. Mandibulofacial Dysostosis and Oculo-Auriculo-Vertebral Spectrum are conditions that share common craniofacial phenotype and present a challenge in arriving at a diagnosis. In this report, we present a case of female proband who was given a differential diagnosis of Treacher Collins syndrome or Hemifacial Microsomia without certainty. Prior genetic testing reported negative for 22q deletion and FGFR screenings. The objective of this study was to demonstrate the critical role of whole-exome sequencing in establishing a genetic diagnosis of the proband. The participants were 14½-year-old affected female proband/parent trio. Proband/parent trio were enrolled in the study. Surgical tissue sample from the proband and parental blood samples were collected and prepared for whole-exome sequencing. Illumina HiSeq 2500 instrument was used for sequencing (125 nucleotide reads/84X coverage). Analyses of variants were performed using custom-developed software, RUNES and VIKING. Variant analyses following whole-exome sequencing identified a heterozygous de novo pathogenic variant, c.259C>T (p.Gln87*), in EFTUD2 (NM_004247.3) gene in the proband. Previous studies have reported that the variants in EFTUD2 gene were associated with Mandibulofacial Dysostosis with Microcephaly. Patients with facial asymmetry, micrognathia, choanal atresia and microcephaly should be analyzed for variants in EFTUD2 gene. Next-generation sequencing techniques, such as whole-exome sequencing offer great promise to improve the understanding of etiologies of sporadic genetic diseases. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Weighted gene co-expression network analysis of expression data of monozygotic twins identifies specific modules and hub genes related to BMI.

Science.gov (United States)

Wang, Weijing; Jiang, Wenjie; Hou, Lin; Duan, Haiping; Wu, Yili; Xu, Chunsheng; Tan, Qihua; Li, Shuxia; Zhang, Dongfeng

2017-11-13

The therapeutic management of obesity is challenging, hence further elucidating the underlying mechanisms of obesity development and identifying new diagnostic biomarkers and therapeutic targets are urgent and necessary. Here, we performed differential gene expression analysis and weighted gene co-expression network analysis (WGCNA) to identify significant genes and specific modules related to BMI based on gene expression profile data of 7 discordant monozygotic twins. In the differential gene expression analysis, it appeared that 32 differentially expressed genes (DEGs) were with a trend of up-regulation in twins with higher BMI when compared to their siblings. Categories of positive regulation of nitric-oxide synthase biosynthetic process, positive regulation of NF-kappa B import into nucleus, and peroxidase activity were significantly enriched within GO database and NF-kappa B signaling pathway within KEGG database. DEGs of NAMPT, TLR9, PTGS2, HBD, and PCSK1N might be associated with obesity. In the WGCNA, among the total 20 distinct co-expression modules identified, coral1 module (68 genes) had the strongest positive correlation with BMI (r = 0.56, P = 0.04) and disease status (r = 0.56, P = 0.04). Categories of positive regulation of phospholipase activity, high-density lipoprotein particle clearance, chylomicron remnant clearance, reverse cholesterol transport, intermediate-density lipoprotein particle, chylomicron, low-density lipoprotein particle, very-low-density lipoprotein particle, voltage-gated potassium channel complex, cholesterol transporter activity, and neuropeptide hormone activity were significantly enriched within GO database for this module. And alcoholism and cell adhesion molecules pathways were significantly enriched within KEGG database. Several hub genes, such as GAL, ASB9, NPPB, TBX2, IL17C, APOE, ABCG4, and APOC2 were also identified. The module eigengene of saddlebrown module (212 genes) was also significantly

Twin-to-twin transfusion syndrome : from placental anastomoses to long-term outcome

NARCIS (Netherlands)

Lopriore, Enrico

2006-01-01

Twin-to-twin transfusion syndrome (TTTS) is a severe complication of monochorionic twin pregnancies associated with high perinatal mortality and morbidity rates. Placental vascular anastomoses, almost invariably present in monochorionic placentas, are the essential anatomical substrate for the

Is that me or my twin? Lack of self-face recognition advantage in identical twins.

Directory of Open Access Journals (Sweden)

Matteo Martini

Full Text Available Despite the increasing interest in twin studies and the stunning amount of research on face recognition, the ability of adult identical twins to discriminate their own faces from those of their co-twins has been scarcely investigated. One's own face is the most distinctive feature of the bodily self, and people typically show a clear advantage in recognizing their own face even more than other very familiar identities. Given the very high level of resemblance of their faces, monozygotic twins represent a unique model for exploring self-face processing. Herein we examined the ability of monozygotic twins to distinguish their own face from the face of their co-twin and of a highly familiar individual. Results show that twins equally recognize their own face and their twin's face. This lack of self-face advantage was negatively predicted by how much they felt physically similar to their co-twin and by their anxious or avoidant attachment style. We speculate that in monozygotic twins, the visual representation of the self-face overlaps with that of the co-twin. Thus, to distinguish the self from the co-twin, monozygotic twins have to rely much more than control participants on the multisensory integration processes upon which the sense of bodily self is based. Moreover, in keeping with the notion that attachment style influences perception of self and significant others, we propose that the observed self/co-twin confusion may depend upon insecure attachment.

Twin RSA

OpenAIRE

Lenstra, Arjen K.; Weger, De; Benjamin, M. M.

2005-01-01

We introduce Twin RSA, pairs of RSA moduli (n, n+ 2), and formulate several questions related to it. Our main questions are: is Twin RSA secure, and what is it good for? © Springer-Verlag Berlin Heidelberg 2005.

Two wide-angle imaging neutral-atom spectrometers (TWINS)

International Nuclear Information System (INIS)

McComas, D.J.; Blake, B.; Burch, J.

1998-01-01

Two Wide-angle Imaging Neutral-atom Spectrometers (TWINS) is a revolutionary new mission designed to stereoscopically image the magnetosphere in charge exchange neutral atoms for the first time. The authors propose to fly two identical TWINS instruments as a mission of opportunity on two widely-spaced high-altitude, high-inclination US Government spacecraft. Because the spacecraft are funded independently, TWINS can provide a vast quantity of high priority science observations (as identified in an ongoing new missions concept study and the Sun-Earth Connections Roadmap) at a small fraction of the cost of a dedicated mission. Because stereo observations of the near-Earth space environs will provide a particularly graphic means for visualizing the magnetosphere in action, and because of the dedication and commitment of the investigator team to the principles of carrying space science to the broader audience, TWINS will also be an outstanding tool for public education and outreach

Intra-uterine exposure to dual fetal programming sequences among surviving co-twins.

Science.gov (United States)

Salihu, Hamisu M; Ibrahimou, Boubakari; Dagne, Getachew A

2011-01-01

The dynamics of fetal programming following in utero demise of a co-twin are poorly understood. The authors examined fetal programming using a unique application of the change-point analysis method, and identified two types of fetal programming that occurred when a viable twin sibling died in utero, while the co-twin survived. In one type, the initial twin fetal programming trajectory was maintained while in a subset of surviving co-twins a "switch" from a twin to a singleton fetal program (dual fetal programming exposure) was observed. The results suggest that the timing in utero of conversion from a twin to a singleton programming pattern occurred slightly earlier among opposite-sex than in same-sex surviving co-twins. For the conversion from a twin to a singleton program to happen, the surviving co-twin must have attained a "critical mass" when the twin sibling died. Whereas, for same-sex surviving co-twins the critical mass for conversion was the 80th percentile of gestational-age specific birth weight, opposite-sex surviving co-twins converted at a lower critical mass (70th percentile). These novel findings warrant further study to confirm the new hithertofore unknown phenomenon of dual fetal programming sequence, and to determine the implications in terms of subsequent morbidity or mortality during infancy, childhood and adult life.

Sports pairs: insights on athletic talent; research reviews: twins with leukemia; parents and twins.

Science.gov (United States)

Segal, Nancy L

2007-06-01

Twin research exploring genetic and environmental influences on athletic interests and talents is reviewed. Illustrative examples of twin athletes representing a variety of sports activities are presented. This is followed by an overview of twin studies offering critical insights into the onset and progress of leukemia. In the last section, timely events involving twins and parents of twins will be described--each case provides a new look at an old question.

Twin Loss: Implications for Counselors Working with Surviving Twins.(practice & Theory)

Science.gov (United States)

Withrow, Rebecca; Schwiebert, Valerie L.

2005-01-01

Multiple births are becoming increasingly prevalent due to the use of fertility drugs and women choosing to wait until later life to conceive. With the growth in the twin population, little research has been done to investigate the effects on the grief process when 1 twin dies. Counselors must understand the unique experience of twins to formulate…

Twelve novel HGD gene variants identified in 99 alkaptonuria patients: focus on 'black bone disease' in Italy.

Science.gov (United States)

Nemethova, Martina; Radvanszky, Jan; Kadasi, Ludevit; Ascher, David B; Pires, Douglas E V; Blundell, Tom L; Porfirio, Berardino; Mannoni, Alessandro; Santucci, Annalisa; Milucci, Lia; Sestini, Silvia; Biolcati, Gianfranco; Sorge, Fiammetta; Aurizi, Caterina; Aquaron, Robert; Alsbou, Mohammed; Lourenço, Charles Marques; Ramadevi, Kanakasabapathi; Ranganath, Lakshminarayan R; Gallagher, James A; van Kan, Christa; Hall, Anthony K; Olsson, Birgitta; Sireau, Nicolas; Ayoob, Hana; Timmis, Oliver G; Sang, Kim-Hanh Le Quan; Genovese, Federica; Imrich, Richard; Rovensky, Jozef; Srinivasaraghavan, Rangan; Bharadwaj, Shruthi K; Spiegel, Ronen; Zatkova, Andrea

2016-01-01

Alkaptonuria (AKU) is an autosomal recessive disorder caused by mutations in homogentisate-1,2-dioxygenase (HGD) gene leading to the deficiency of HGD enzyme activity. The DevelopAKUre project is underway to test nitisinone as a specific treatment to counteract this derangement of the phenylalanine-tyrosine catabolic pathway. We analysed DNA of 40 AKU patients enrolled for SONIA1, the first study in DevelopAKUre, and of 59 other AKU patients sent to our laboratory for molecular diagnostics. We identified 12 novel DNA variants: one was identified in patients from Brazil (c.557T>A), Slovakia (c.500C>T) and France (c.440T>C), three in patients from India (c.469+6T>C, c.650-85A>G, c.158G>A), and six in patients from Italy (c.742A>G, c.614G>A, c.1057A>C, c.752G>A, c.119A>C, c.926G>T). Thus, the total number of potential AKU-causing variants found in 380 patients reported in the HGD mutation database is now 129. Using mCSM and DUET, computational approaches based on the protein 3D structure, the novel missense variants are predicted to affect the activity of the enzyme by three mechanisms: decrease of stability of individual protomers, disruption of protomer-protomer interactions or modification of residues in the region of the active site. We also present an overview of AKU in Italy, where so far about 60 AKU cases are known and DNA analysis has been reported for 34 of them. In this rather small group, 26 different HGD variants affecting function were described, indicating rather high heterogeneity. Twelve of these variants seem to be specific for Italy.

Genome-wide association study of primary tooth eruption identifies pleiotropic loci associated with height and craniofacial distances

DEFF Research Database (Denmark)

Fatemifar, Ghazaleh; Hoggart, Clive J; Paternoster, Lavinia

2013-01-01

Twin and family studies indicate that the timing of primary tooth eruption is highly heritable, with estimates typically exceeding 80%. To identify variants involved in primary tooth eruption, we performed a population-based genome-wide association study of 'age at first tooth' and 'number of teeth......' using 5998 and 6609 individuals, respectively, from the Avon Longitudinal Study of Parents and Children (ALSPAC) and 5403 individuals from the 1966 Northern Finland Birth Cohort (NFBC1966). We tested 2 446 724 SNPs imputed in both studies. Analyses were controlled for the effect of gestational age, sex...

Nephrolithiasis in identical twins: the impact of nature vs nurture.

Science.gov (United States)

Haleblian, George E; Cantor, David A; Sur, Roger L; Assimos, Dean G; Preminger, Glenn M

2007-09-01

To assess possible underlying metabolic abnormalities in three sets of monozygotic twins, to evaluate the interplay among the factors of kidney stone formation, a complex multifactorial process influenced by environmental, genetic and anatomical factors. Three sets of identical twins with either cystine or calcium oxalate stones were identified. Demographic data, medical histories and the results of 24-h urine testing, with samples collected on self-selected diets, were reviewed and analysed. The cystinuric twins had very similar cystine excretion rates, while stone activity was significantly more pronounced in one. Metabolic abnormalities were concordant in one set of twins with calcium oxalate stones, both being hypercalciuric and hyperuricosuric. However, metabolic abnormalities were discordant in the other pair, one twin with hypercalciuria and the other with hypocitraturia. Two of the three pairs had low urinary volume. These results support previous observations that environmental, genetic and potentially, anatomical factors play roles in kidney-stone formation. Additional controlled studies of monozygotic stone-forming twins might help to define the interplay between environmental and genetic factors, and allow the identification of susceptibility genes involved in stone generation.

Needle twins and right-angled twins in minerals: comparison between experiment and theory

Science.gov (United States)

Salje, E.K.H.; Buckley, A.; Van Tendeloo, G.; Ishibashi, Y.; Nord, G.L.

1998-01-01

Transformation twinning in minerals forms isolated twin walls, intesecting walls with corner junctions, and wedge-shaped twins as elements of hierarchical patterns. When cut perpendicular to the twin walls, the twins have characteristic shapes, right-angled and needle-shaped wall traces, which can be observed by transmission electron microscopy or by optical microscopy. Theoretical geometries of wall shapes recently derived for strain-related systems should hold for most displacive and order-disorder type phase transitions: 1) right-angled twins show curved junctions; 2) needle-shaped twins contain flat wall segments near the needle tip if the elastic behaviour of the mineral is dominated by its anisotroyp; 3) additional bending forces and pinning effects lead to curved walls near the junction that make the needle tip appear more blunt. Bent right-angled twins were analyzed in Gd2(MoO4)3. Linear needle tips were found in WO3, [N(CH3)4]2.ZnBr4 CrAl, BiVO4, GdBa2Cu3O7, and PbZrO. Parabolic tips occur in K2Ba(NO2)4, and GeTe whereas exponential curvatures appear in BaTiO3, KSCN, Pb3(PO4)2, CaTiO3, alkali feldspars, YBa2Cu3O7, and MnAl. The size and shape of the twin microstructure relates to its formation during the phase transition and the subsequent annealing history. The mobility of the twin walls after formation depends not only on the thermal activation but also on the structure of the wall, which may be pinned to impurities on a favorable structural site. Depinnign energies are often large compared with thermal energies for diffusion. This leads to kinetic time scales for twin coarsening that are comparable to geological time scales. Therefore, transformation twins that exhibit needle domains not only indicate that the mineral underwent a structural phase transition but also contain information about its subsequent geological history.

A frameshift variant of CYP2C8 was identified in a patient who suffered from rhabdomyolysis after administration of cerivastatin.

Science.gov (United States)

Ishikawa, Chikako; Ozaki, Hiroshi; Nakajima, Toshiaki; Ishii, Toshihiro; Kanai, Saburo; Anjo, Saeko; Shirai, Kohji; Inoue, Ituro

2004-01-01

A hypercholesterolemic patient medicated with cerivastatin for 22 days resulted in acute rhabdomyolysis. CYP2C8 and CYP3A4 are the major enzymes responsible for the metabolism of cerivastatin, and a transporter, OATP2, contributes to uptake of cerivastatin to the liver. In this study, the patient's DNA was sequenced in order to identify a variant that would lead to the adverse effect of cerivastatin. Three nucleotide variants, 475delA, G874C, and T1551C, were found in the exons of CYP2C8. The patient was homozygous for 475delA variant that leads to frameshift and premature termination. Accordingly, the patient is most likely lacking the enzyme activity. The patient's children were both heterozygous for the mutation. The patient had three nucleotide variants in exon 4 (A388G) and exon 5 (C571T and C597T) of OATP2 that were all heterozygous. No nucleotide variation in the exons of CYP3A4 was identified. To our knowledge, this is the first report showing that the adverse effect of cerivastatin might be caused by the genetic variant of CYP2C8.

Polygenic analysis of genome-wide SNP data identifies common variants on allergic rhinitis

DEFF Research Database (Denmark)

Mohammadnejad, Afsaneh; Brasch-Andersen, Charlotte; Haagerup, Annette

Background: Allergic Rhinitis (AR) is a complex disorder that affects many people around the world. There is a high genetic contribution to the development of the AR, as twins and family studies have estimated heritability of more than 33%. Due to the complex nature of the disease, single SNP...... analysis has limited power in identifying the genetic variations for AR. We combined genome-wide association analysis (GWAS) with polygenic risk score (PRS) in exploring the genetic basis underlying the disease. Methods: We collected clinical data on 631 Danish subjects with AR cases consisting of 434...... sibling pairs and unrelated individuals and control subjects of 197 unrelated individuals. SNP genotyping was done by Affymetrix Genome-Wide Human SNP Array 5.0. SNP imputation was performed using "IMPUTE2". Using additive effect model, GWAS was conducted in discovery sample, the genotypes...

Epigenetic differences in monozygotic twins discordant for major depressive disorder.

Science.gov (United States)

Malki, K; Koritskaya, E; Harris, F; Bryson, K; Herbster, M; Tosto, M G

2016-06-14

Although monozygotic (MZ) twins share the majority of their genetic makeup, they can be phenotypically discordant on several traits and diseases. DNA methylation is an epigenetic mechanism that can be influenced by genetic, environmental and stochastic events and may have an important impact on individual variability. In this study we explored epigenetic differences in peripheral blood samples in three MZ twin studies on major depressive disorder (MDD). Epigenetic data for twin pairs were collected as part of a previous study using 8.1-K-CpG microarrays tagging DNA modification in white blood cells from MZ twins discordant for MDD. Data originated from three geographical regions: UK, Australia and the Netherlands. Ninety-seven MZ pairs (194 individuals) discordant for MDD were included. Different methods to address non independently-and-identically distributed (non-i.i.d.) data were evaluated. Machine-learning methods with feature selection centered on support vector machine and random forest were used to build a classifier to predict cases and controls based on epivariations. The most informative variants were mapped to genes and carried forward for network analysis. A mixture approach using principal component analysis (PCA) and Bayes methods allowed to combine the three studies and to leverage the increased predictive power provided by the larger sample. A machine-learning algorithm with feature reduction classified affected from non-affected twins above chance levels in an independent training-testing design. Network analysis revealed gene networks centered on the PPAR-γ (NR1C3) and C-MYC gene hubs interacting through the AP-1 (c-Jun) transcription factor. PPAR-γ (NR1C3) is a drug target for pioglitazone, which has been shown to reduce depression symptoms in patients with MDD. Using a data-driven approach we were able to overcome challenges of non-i.i.d. data when combining epigenetic studies from MZ twins discordant for MDD. Individually, the studies yielded

Meta-analysis identifies common and rare variants influencing blood pressure and overlapping with metabolic trait loci

NARCIS (Netherlands)

Liu, C. (Chunyu); A. Kraja (Aldi); J.A. Smith (Jennifer A); J. Brody (Jennifer); N. Franceschini (Nora); J.C. Bis (Joshua); K.M. Rice (Kenneth); A.C. Morrison (Alanna); Y. Lu (Yingchang); Weiss, S. (Stefan); X. Guo (Xiuqing); W. Palmas (Walter); L.W. Martin (Lisa); Y.D. Chen (Y.); Surendran, P. (Praveen); F. Drenos (Fotios); Cook, J.P. (James P.); P. Auer (Paul); A.Y. Chu (Audrey); Giri, A. (Ayush); Zhao, W. (Wei); M. Jakobsdottir (Margret); Lin, L.-A. (Li-An); J.M. Stafford (Jeanette M.); N. Amin (Najaf); Mei, H. (Hao); J. Yao (Jiefen); J.M. Voorman (Jeanine); M.G. Larson (Martin); M.L. Grove (Megan); A.V. Smith (Albert Vernon); S.J. Hwang; H. Chen (Han); T. Huan (Tianxiao); Kosova, G. (Gulum); N.O. Stitziel (Nathan); S. Kathiresan (Sekar); N.J. Samani (Nilesh); H. Schunkert (Heribert); P. Deloukas (Panagiotis); M. Li (Man); C. Fuchsberger (Christian); C. Pattaro (Cristian); M. Gorski (Mathias); C. Kooperberg (Charles); G. Papanicolaou (George); Rossouw, J.E. (Jacques E.); J.D. Faul (Jessica D.); S.L.R. Kardia (Sharon); C. Bouchard (Claude); L.J. Raffel (Leslie); Uitterlinden, A.G. (André G.); O.H. Franco (Oscar); R. Vasan (Ramachandran); C.J. O'Donnell (Christopher); K.D. Taylor (Kent); K.Y. Liu; E.P. Bottinger (Erwin); R.F. Gottesman (Rebecca); E.W. Daw (E. Warwick); F. Giulianini (Franco); S.K. Ganesh (Santhi); E. Salfati (Elias); T.B. Harris (Tamara); Launer, L.J. (Lenore J.); M. Dörr (Marcus); S.B. Felix (Stephan); R. Rettig (Rainer); H. Völzke (Henry); E. Kim (Eric); W.-J. Lee (Wen-Jane); I.T. Lee; Sheu, W.H.-H. (Wayne H.-H.); Tsosie, K.S. (Krystal S.); Edwards, D.R.V. (Digna R. Velez); Y. Liu (YongMei); Correa, A. (Adolfo); D.R. Weir (David); U. Völker (Uwe); P.M. Ridker (Paul); E.A. Boerwinkle (Eric); V. Gudnason (Vilmundur); A. Reiner (Alexander); Van Duijn, C.M. (Cornelia M.); I.B. Borecki (Ingrid); T.L. Edwards (Todd L.); A. Chakravarti (Aravinda); Rotter, J.I. (Jerome I.); B.M. Psaty (Bruce); R.J.F. Loos (Ruth); M. Fornage (Myriam); G.B. Ehret (Georg); C. Newton-Cheh (Christopher); D. Levy (Daniel); D.I. Chasman (Daniel)

2016-01-01

textabstractMeta-analyses of association results for blood pressure using exome-centric single-variant and gene-based tests identified 31 new loci in a discovery stage among 146,562 individuals, with follow-up and meta-analysis in 180,726 additional individuals (total n = 327,288). These blood

Diabetes and perinatal mortality in twin pregnancies.

Directory of Open Access Journals (Sweden)

Zhong-Cheng Luo

Full Text Available BACKGROUND: Diabetes in pregnancy has been associated with a paradoxically reduced risk of neonatal death in twin pregnancies. Risk "shift" may be a concern in that the reduction in neonatal deaths may be due to an increase in fetal deaths (stillbirths. This study aimed to clarify the impact of diabetes on the risk of perinatal death (neonatal death plus stillbirth in twin pregnancies. METHODS: This was a retrospective cohort study of twin births using the largest available dataset on twin births (the U.S. matched multiple birth data 1995-2000; 19,676 neonates from diabetic pregnancies, 541,481 from non-diabetic pregnancies. Cox proportional hazard models were applied to estimate the adjusted hazard ratios (aHR of perinatal death accounting for twin cluster-level dependence. RESULTS: Comparing diabetic versus non-diabetic twin pregnancies, overall perinatal mortality rate was counterintuitively lower [2.1% versus 3.3%, aHR 0.70 (95% confidence intervals 0.63-0.78]. Individually, both stillbirth and neonatal mortality rates were lower in diabetic pregnancies, but we identified significant differences by gestational age and birth weight. Diabetes was associated with a survival benefit in pregnancies completed before 32 weeks [aHR 0.55 (0.48-0.63] or with birth weight =2500 g [aHR 2.20 (1.55-3.13]. CONCLUSIONS: Diabetes in pregnancy appears to be "protective" against perinatal death in twin pregnancies ending in very preterm or very low birth weight births. Prospective studies are required to clarify whether these patterns of risk are real, or they are artifacts of unmeasured confounders. Additional data correlating these outcomes with the types of diabetes in pregnancy are also needed to distinguish the effects of pre-gestational vs. gestational diabetes.

One half living for two: cross-cultural paradigms of twinship and twin loss.

Science.gov (United States)

McIlroy, Emily C

Many indigenous African religions, specifically that of the Yoruba of Nigeria, the Bamana and Malinke of Mali, and the Nuer of southern Sudan, are characterized by a system of spiritual beliefs surrounding the life and death of twins. Separation by death poses an extreme threat to the soul(s) of twins, and many rituals and customs designed to sustain the spirit of surviving twins are widely practiced. Despite twin loss being overlooked in Western psychological studies of grief, recent research and in-depth interviews of bereaved twins clearly identifies the unique nature of losing a twin, and the importance of acknowledging this distinction in the surviving twin's ability to cope with the death. The spiritual practices of the Yoruba, Bamana, Malinke, and Nuer are conducive to dealing with the specific nature of twin loss. They take into account the uniqueness of the twinship experience, and provide material for reflection on healing approaches outside the traditional parameters of psychology.

Ventricular strain changes in monochorionic twins with and without twin-to-twin transfusion syndrome.

Science.gov (United States)

Taylor-Clarke, Marisa C; Matsui, Hikoro; Roughton, Michael; Wimalasundera, Ruwan C; Gardiner, Helena M

2013-06-01

The objective of the study was to investigate whether vector velocity imaging (VVI), a non-Doppler speckle tracking ultrasound technology, is feasible in twin pregnancies and can aid management of twin-twin transfusion syndrome (TTTS). Twenty-seven women pregnant with monochorionic diamniotic twins affected by TTTS and 28 monochorionic pregnancies that did not develop TTTS were included in a prospective case-control study at a fetal medicine center. Fetal echocardiograms were recorded with dummy electrocardiography to retain original frame rates when exported for offline speckle tracking analysis using Syngo-VVI software (Siemens Corp, Munich, Germany). Right and left ventricular (LV) free wall Lagrangian strain was measured from the original coordinates. Within-twin pair ventricular strain differences including relationship to Quintero staging and response to laser therapy for TTTS were analyzed by Wilcoxon signed-rank test. The VVI strain measurements could be analyzed in 182 of 200 TTTS and 96 of 112 non-TTTS control ventricles. Within-pair strain was concordant in non-TTTS controls. Recipient LV strain was reduced at all Quintero stages compared with donors (P < .01). Recipient right ventricular strain was reduced only in stages 3 and 4 (P < .01). Strain improved at a median of 2 weeks following successful laser therapy. Intertwin differences in strain were independent of weight discordance. Recipient LV strain is reduced in stages 1 and 2 TTTS. Within-pair strain discordance may distinguish early TTTS from growth discordance and guide timing of and management following treatment. Copyright © 2013 Mosby, Inc. All rights reserved.

Allele frequencies of variants in ultra conserved elements identify selective pressure on transcription factor binding.

Directory of Open Access Journals (Sweden)

Toomas Silla

Full Text Available Ultra-conserved genes or elements (UCGs/UCEs in the human genome are extreme examples of conservation. We characterized natural variations in 2884 UCEs and UCGs in two distinct populations; Singaporean Chinese (n = 280 and Italian (n = 501 by using a pooled sample, targeted capture, sequencing approach. We identify, with high confidence, in these regions the abundance of rare SNVs (MAF5% are more often found in relatively less-conserved nucleotides within UCEs, compared to rare variants. Moreover, prevalent variants are less likely to overlap transcription factor binding site. Using SNPfold we found no significant influence of RNA secondary structure on UCE conservation. All together, these results suggest UCEs are not under selective pressure as a stretch of DNA but are under differential evolutionary pressure on the single nucleotide level.

Twin pregnancy

DEFF Research Database (Denmark)

Sperling, Lene; Tabor, A

2001-01-01

Determination of chorionicity is one of the most important issues in the management of twin pregnancy. Modern ultrasound equipment has made it possible to accurately assess placentation already in the first trimester with the lambda sign. With regard to prenatal diagnosis, it is important to know...... for clinicians caring for twin pregnancies....

Marital status and twins' health and behavior: an analysis of middle-aged Danish twins

DEFF Research Database (Denmark)

Osler, Merete; McGue, Matt; Lund, Rikke

2008-01-01

mass index (BMI), depression symptoms, self-rated health, cognitive function, physical activity, smoking, and alcohol intake. RESULTS: Among all 2350 individual twins, men who were divorced/widowed or never married had higher depression scores, lower cognitive test scores, lower physical activity....../widowed twin had higher average depression scores and was more likely to be a smoker. Never married twins had lower physical activity scores and never married male twins had higher BMI and higher depression scores than their married co-twin. CONCLUSION: This study suggests that the relationships of adult...... divorce with depression and smoking in Danish twins are due to the stressful effects of marital dissolution, but that marital differences in other health and behavioral outcomes are most consistent with selection effects related to genetic or rearing environmental factors....

Twelve novel HGD gene variants identified in 99 alkaptonuria patients: focus on ‘black bone disease' in Italy

Science.gov (United States)

Nemethova, Martina; Radvanszky, Jan; Kadasi, Ludevit; Ascher, David B; Pires, Douglas E V; Blundell, Tom L; Porfirio, Berardino; Mannoni, Alessandro; Santucci, Annalisa; Milucci, Lia; Sestini, Silvia; Biolcati, Gianfranco; Sorge, Fiammetta; Aurizi, Caterina; Aquaron, Robert; Alsbou, Mohammed; Marques Lourenço, Charles; Ramadevi, Kanakasabapathi; Ranganath, Lakshminarayan R; Gallagher, James A; van Kan, Christa; Hall, Anthony K; Olsson, Birgitta; Sireau, Nicolas; Ayoob, Hana; Timmis, Oliver G; Le Quan Sang, Kim-Hanh; Genovese, Federica; Imrich, Richard; Rovensky, Jozef; Srinivasaraghavan, Rangan; Bharadwaj, Shruthi K; Spiegel, Ronen; Zatkova, Andrea

2016-01-01

Alkaptonuria (AKU) is an autosomal recessive disorder caused by mutations in homogentisate-1,2-dioxygenase (HGD) gene leading to the deficiency of HGD enzyme activity. The DevelopAKUre project is underway to test nitisinone as a specific treatment to counteract this derangement of the phenylalanine-tyrosine catabolic pathway. We analysed DNA of 40 AKU patients enrolled for SONIA1, the first study in DevelopAKUre, and of 59 other AKU patients sent to our laboratory for molecular diagnostics. We identified 12 novel DNA variants: one was identified in patients from Brazil (c.557T>A), Slovakia (c.500C>T) and France (c.440T>C), three in patients from India (c.469+6T>C, c.650–85A>G, c.158G>A), and six in patients from Italy (c.742A>G, c.614G>A, c.1057A>C, c.752G>A, c.119A>C, c.926G>T). Thus, the total number of potential AKU-causing variants found in 380 patients reported in the HGD mutation database is now 129. Using mCSM and DUET, computational approaches based on the protein 3D structure, the novel missense variants are predicted to affect the activity of the enzyme by three mechanisms: decrease of stability of individual protomers, disruption of protomer-protomer interactions or modification of residues in the region of the active site. We also present an overview of AKU in Italy, where so far about 60 AKU cases are known and DNA analysis has been reported for 34 of them. In this rather small group, 26 different HGD variants affecting function were described, indicating rather high heterogeneity. Twelve of these variants seem to be specific for Italy. PMID:25804398

Biparental inheritance of chromosomal abnormalities in male twins with non-syndromic mental retardation

DEFF Research Database (Denmark)

Nielsen, Mette Gilling; Lind-Thomsen, Allan; Mang, Yuan

2011-01-01

In a monozygotic twin couple with mental retardation (MR), we identified a maternally inherited inversion and a paternally inherited translocation: 46,XY,inv(10)(p11.2q21.2)mat,t(9;18)(p22;q21.1)pat. The maternally inherited inv(10) was a benign variant without any apparent phenotypical...... implications. The translocation breakpoint at 9p was within a cluster of interferon a genes and the 18q21 breakpoint truncated ZBTB7C (zinc finger and BTB containing 7C gene). In addition, analyses with array-CGH revealed a 931 kb maternally inherited deletion on chromosome 8q22 as well as an 875 kb maternally...... inherited duplication on 5p14. The deletion encompasses the RIM2 (Rab3A-interacting molecule 2), FZD6 (Frizzled homolog 6) and BAALC (Brain and Acute Leukemia Gene, Cytoplasmic) genes and the duplication includes the 5' end of the CDH9 (cadherin 9) gene. Exome sequencing did not reveal any additional...

Register-based research on twins

DEFF Research Database (Denmark)

Christensen, Kaare; Ohm Kyvik, Kirsten; Holm, Niels V

2011-01-01

Introduction: The Danish Twin Registry (DTR) has for more than 50 years been based on surveys and clinical investigations and over the two last decades also on register linkage. Currently these two approaches are merged within Statistics Denmark. Research topics: Here we report on three major...... groups of register-based research in the DTR that used the uniqueness of twinning. First, we focus on the ''long-term prognosis'' of being a twin compared with being a singleton and show that Danish twins have health trajectories in adulthood similar to singletons, which is a result of interest for twins...... illustrate how the co-twin control method in a register setting can be used to control for the effect of rearing environment and genetic factors in studies of the association between exposures and health. CONCLUSION: The spectrum of register-based twin studies is very wide and have changed in accordance...

Weighted gene co-expression network analysis of expression data of monozygotic twins identifies specific modules and hub genes related to BMI

DEFF Research Database (Denmark)

Wang, Weijing; Jiang, Wenjie; Hou, Lin

2017-01-01

BACKGROUND: The therapeutic management of obesity is challenging, hence further elucidating the underlying mechanisms of obesity development and identifying new diagnostic biomarkers and therapeutic targets are urgent and necessary. Here, we performed differential gene expression analysis......) were with a trend of up-regulation in twins with higher BMI when compared to their siblings. Categories of positive regulation of nitric-oxide synthase biosynthetic process, positive regulation of NF-kappa B import into nucleus, and peroxidase activity were significantly enriched within GO database...

Functional Investigations of HNF1A Identify Rare Variants as Risk Factors for Type 2 Diabetes in the General Population

Science.gov (United States)

Najmi, Laeya Abdoli; Aukrust, Ingvild; Flannick, Jason; Molnes, Janne; Burtt, Noel; Molven, Anders; Groop, Leif; Altshuler, David; Johansson, Stefan; Njølstad, Pål Rasmus

2017-01-01

Variants in HNF1A encoding hepatocyte nuclear factor 1α (HNF-1A) are associated with maturity-onset diabetes of the young form 3 (MODY 3) and type 2 diabetes. We investigated whether functional classification of HNF1A rare coding variants can inform models of diabetes risk prediction in the general population by analyzing the effect of 27 HNF1A variants identified in well-phenotyped populations (n = 4,115). Bioinformatics tools classified 11 variants as likely pathogenic and showed no association with diabetes risk (combined minor allele frequency [MAF] 0.22%; odds ratio [OR] 2.02; 95% CI 0.73–5.60; P = 0.18). However, a different set of 11 variants that reduced HNF-1A transcriptional activity to diabetes in the general population (combined MAF 0.22%; OR 5.04; 95% CI 1.99–12.80; P = 0.0007). Our functional investigations indicate that 0.44% of the population carry HNF1A variants that result in a substantially increased risk for developing diabetes. These results suggest that functional characterization of variants within MODY genes may overcome the limitations of bioinformatics tools for the purposes of presymptomatic diabetes risk prediction in the general population. PMID:27899486

Prenatal x-ray exposure and childhood cancer in twins

International Nuclear Information System (INIS)

Harvey, E.B.; Boice, J.D. Jr.; Honeyman, M.; Flannery, J.T.

1985-01-01

A case-control study was conducted to investigate the relation between prenatal exposure to x-rays and childhood cancer, including leukemia, in over 32,000 twins born in Connecticut from 1930 to 1969. Twins as opposed to single births were chosen for study to reduce the likelihood of medical selection bias, since twins were often exposed to x-rays to diagnose the twin pregnancy or to determine fetal positioning before delivery and not because of medical conditions that may conceivably pre-dispose to cancer. Each of 31 incident cases of cancer, identified by linking the Connecticut twin and tumor registries, was matched with four twin controls according to sex, year of birth, and race. Records of hospitals, radiologists, and private physicians were searched for histories of x-ray exposure and other potentially important risk factors. Documented prenatal x-ray exposures were found for 39 per cent of the cases (12 of 31) and for 26 per cent of the controls (28 of 109). No other pregnancy, delivery, or maternal conditions were associated with cancer risk except low birth weight: 38 per cent of the cases as compared with 25 per cent of the controls weighed under 2.27 kg at birth. When birth weight was adjusted for, twins in whom leukemia or other childhood cancer developed were twice as likely to have been exposed to x-rays in utero as twins who were free of disease (relative risk, 2.4; 95 per cent confidence interval, 1.0 to 5.9). The results, though based on small numbers, provide further evidence that low-dose prenatal irradiation may increase the risk of childhood cancer

Birth size and gestational age in opposite-sex twins as compared to same-sex twins

DEFF Research Database (Denmark)

Jelenkovic, Aline; Sund, Reijo; Yokoyama, Yoshie

2018-01-01

It is well established that boys are born heavier and longer than girls, but it remains unclear whether birth size in twins is affected by the sex of their co-twin. We conducted an individual-based pooled analysis of 21 twin cohorts in 15 countries derived from the COllaborative project of Develo......It is well established that boys are born heavier and longer than girls, but it remains unclear whether birth size in twins is affected by the sex of their co-twin. We conducted an individual-based pooled analysis of 21 twin cohorts in 15 countries derived from the COllaborative project....... In girls, birth size was not associated (5 g birth weight; 95% CI -8 to -18 and -0.089 cm birth length; 95% CI -0.202 to 0.025) with the sex of the co-twin. Gestational age was slightly shorter in boy-boy pairs than in boy-girl and girl-girl pairs. When birth size was standardized by gestational age......, the magnitude of the associations was attenuated in boys, particularly for birth weight. In conclusion, boys with a co-twin sister are heavier and longer at birth than those with a co-twin brother. However, these differences are modest and partly explained by a longer gestation in the presence of a co...

Twinning anisotropy of tantalum during nanoindentation

Energy Technology Data Exchange (ETDEWEB)

Goel, Saurav, E-mail: S.GOEL@qub.ac.uk [School of Mechanical and Aerospace Engineering, Queen' s University, Belfast, BT9 5AH (United Kingdom); Beake, Ben [Micro Materials Limited, Willow House, Yale Business Village, Ellice Way, Wrexham LL13 7YL (United Kingdom); Dalton Research Institute, Manchester Metropolitan University, Manchester, M15GD (United Kingdom); Chan, Chi-Wai [School of Mechanical and Aerospace Engineering, Queen' s University, Belfast, BT9 5AH (United Kingdom); Haque Faisal, Nadimul [School of Engineering, Robert Gordon University, Garthdee Road, Aberdeen AB10 7GJ (United Kingdom); Dunne, Nicholas [School of Mechanical and Aerospace Engineering, Queen' s University, Belfast, BT9 5AH (United Kingdom)

2015-03-11

Unlike other BCC metals, the plastic deformation of nanocrystalline Tantalum (Ta) during compression is regulated by deformation twinning. Whether or not this twinning exhibits anisotropy was investigated through simulation of displacement-controlled nanoindentation test using molecular dynamics (MD) simulation. MD data was found to correlate well with the experimental data in terms of surface topography and hardness measurements. The mechanism of the transport of material was identified due to the formation and motion of prismatic dislocations loops (edge dislocations) belonging to the 1/2〈111〉 type and 〈100〉 type Burgers vector family. Further analysis of crystal defects using a fully automated dislocation extraction algorithm (DXA) illuminated formation and migration of twin boundaries on the (110) and (111) orientation but not on the (010) orientation and most importantly after retraction all the dislocations disappeared on the (110) orientation suggesting twinning to dominate dislocation nucleation in driving plasticity in tantalum. A significant finding was that the maximum shear stress (critical Tresca stress) in the deformation zone exceeded the theoretical shear strength of Ta (Shear modulus/2π~10.03 GPa) on the (010) orientation but was lower than it on the (110) and the (111) orientations. In light of this, the conventional lore of assuming the maximum shear stress being 0.465 times the mean contact pressure was found to break down at atomic scale.

Factors that affect skin aging: a cohort-based survey on twins.

Science.gov (United States)

Martires, Kathryn J; Fu, Pingfu; Polster, Amy M; Cooper, Kevin D; Baron, Elma D

2009-12-01

To identify environmental factors that correlate with skin photoaging, controlling for genetic susceptibility by using a questionnaire administered to twins. The survey collected information about each participant's Fitzpatrick type, history of skin cancer, smoking and drinking habits, and weight from a cohort of twins. Clinicians then assigned a clinical photodamage score to each participant. The annual Twins Days Festival in Twinsburg, Ohio. A voluntary cohort of twins from the general community, mostly from Ohio, Pennsylvania, and the northeastern United States. The survey was completed on a voluntary basis by sets of monozygotic (MZ) and dizygotic (DZ) twins. A total of 130 surveys taken by 65 complete twin pairs were analyzed. Skin aging was assessed using a validated photographic scale of photodamage, graded by such characteristics as wrinkling and pigmentation change. Photodamage scores among twins of a pair, whether MZ or DZ, were highly correlated (P = .92). Factors found to predict higher photodamage include history of skin cancer (P < .001), zygosity status (MZ vs DZ) (P = .001), weight (P = .02), and cigarette smoking (P = .046). Alcohol consumption was significantly associated with lower photodamage scores (P = .003). The study of twins provides a unique opportunity to control for genetic susceptibility in order to elucidate environmental influences on skin aging. The relationships found between smoking, weight, sunscreen use, skin cancer, and photodamage in these twin pairs may help to motivate the reduction of risky behaviors.

Salt-Sensitive Hypertension and Cardiac Hypertrophy in Transgenic Mice Expressing a Corin Variant Identified in African Americans

Science.gov (United States)

Wang, Wei; Cui, Yujie; Shen, Jianzhong; Jiang, Jingjing; Chen, Shenghan; Peng, Jianhao; Wu, Qingyu

2012-01-01

African Americans represent a high risk population for salt-sensitive hypertension and heart disease but the underlying mechanism remains unclear. Corin is a cardiac protease that regulates blood pressure by activating natriuretic peptides. A corin gene variant (T555I/Q568P) was identified in African Americans with hypertension and cardiac hypertrophy. In this study, we test the hypothesis that the corin variant contributes to the hypertensive and cardiac hypertrophic phenotype in vivo. Transgenic mice were generated to express wild-type or T555I/Q568P variant corin in the heart under the control of α-myosin heavy chain promoter. The mice were crossed into a corin knockout background to create KO/TgWT and KO/TgV mice that expressed WT or variant corin, respectively, in the heart. Functional studies showed that KO/TgV mice had significantly higher levels of pro-atrial natriuretic peptide in the heart compared with that in control KO/TgWT mice, indicating that the corin variant was defective in processing natriuretic peptides in vivo. By radiotelemetry, corin KO/TgV mice were found to have hypertension that was sensitive to dietary salt loading. The mice also developed cardiac hypertrophy at 12–14 months of age when fed a normal salt diet or at a younger age when fed a high salt diet. The phenotype of salt-sensitive hypertension and cardiac hypertrophy in KO/TgV mice closely resembles the pathological findings in African Americans who carry the corin variant. The results indicate that corin defects may represent an important mechanism in salt-sensitive hypertension and cardiac hypertrophy in African Americans. PMID:22987923

Infertility, infertility treatment and twinning: the Danish National Birth Cohort

DEFF Research Database (Denmark)

Zhu, Jin Liang; Basso, Olga; Obel, Carsten

2007-01-01

BACKGROUND: We have previously observed that an increasing time to pregnancy (TTP) is associated with a reduced frequency of twin deliveries in couples not receiving infertility treatment. By using updated information, we assessed the frequencies of dizygotic (DZ) and monozygotic (MZ) twin...... deliveries as a function of infertility (TTP > 12 months), as well as infertility treatment. METHODS: From the Danish National Birth Cohort (1997-2003), we identified 51 730 fertile couples with TTP 12 months and 5163 infertile couples who conceived after treatment. Information on zygosity, available...... for part of the cohort (1997-2000), was based on standardized questions on the similarities between the twins at the age of 3-5 years. RESULTS: Compared with fertile couples, the frequency of DZ twin deliveries was lower for infertile couples conceiving naturally (odds ratio 0.4, 95% confidence interval 0...

Infertility, infertility treatment and twinning: the Danish National BirthCohort

DEFF Research Database (Denmark)

Zhu, Jin Liang; Basso, Olga; Obel, Carsten

2007-01-01

BACKGROUND We have previously observed that an increasing time to pregnancy (TTP) is associated with a reduced frequency of twin deliveries in couples not receiving infertility treatment. By using updated information, we assessed the frequencies of dizygotic (DZ) and monozygotic (MZ) twin...... deliveries as a function of infertility (TTP>12 months), as well as infertility treatment. METHODS From the Danish National Birth Cohort (1997-2003), we identified 51 730 fertile couples with TTPwith TTP>12 months and 5163 infertile couples who conceived after treatment. Information on zygosity, available...... for part of the cohort (1997-2000), was based on standardized questions on the similarities between the twins at the age of 3-5 years. RESULTS Compared with fertile couples, the frequency of DZ twin deliveries was lower for infertile couples conceiving naturally (odds ratio 0.4, 95% confidence interval 0...

Genome-wide association study of blood pressure extremes identifies variant near UMOD associated with hypertension.

Directory of Open Access Journals (Sweden)

Sandosh Padmanabhan

2010-10-01

Full Text Available Hypertension is a heritable and major contributor to the global burden of disease. The sum of rare and common genetic variants robustly identified so far explain only 1%-2% of the population variation in BP and hypertension. This suggests the existence of more undiscovered common variants. We conducted a genome-wide association study in 1,621 hypertensive cases and 1,699 controls and follow-up validation analyses in 19,845 cases and 16,541 controls using an extreme case-control design. We identified a locus on chromosome 16 in the 5' region of Uromodulin (UMOD; rs13333226, combined P value of 3.6 × 10⁻¹¹. The minor G allele is associated with a lower risk of hypertension (OR [95%CI]: 0.87 [0.84-0.91], reduced urinary uromodulin excretion, better renal function; and each copy of the G allele is associated with a 7.7% reduction in risk of CVD events after adjusting for age, sex, BMI, and smoking status (H.R. = 0.923, 95% CI 0.860-0.991; p = 0.027. In a subset of 13,446 individuals with estimated glomerular filtration rate (eGFR measurements, we show that rs13333226 is independently associated with hypertension (unadjusted for eGFR: 0.89 [0.83-0.96], p = 0.004; after eGFR adjustment: 0.89 [0.83-0.96], p = 0.003. In clinical functional studies, we also consistently show the minor G allele is associated with lower urinary uromodulin excretion. The exclusive expression of uromodulin in the thick portion of the ascending limb of Henle suggests a putative role of this variant in hypertension through an effect on sodium homeostasis. The newly discovered UMOD locus for hypertension has the potential to give new insights into the role of uromodulin in BP regulation and to identify novel drugable targets for reducing cardiovascular risk.

The accuracy of self-reported history of seizures in Danish, Norwegian and U.S. twins

DEFF Research Database (Denmark)

Corey, Linda A; Kjeldsen, Marianne J; Solaas, Marit H

2009-01-01

. The accuracy of these reports was assessed. Self-reported epilepsy was verified in 81.9% of twins overall (86.1% (DTR), 75.6% (NTR) and 80.7% (MATR)). However, when both pair members reported a history of epilepsy in the affected pair member, epilepsy was verified in >90% of cases. Among MATR twins...... of this approach in identifying true cases. Information on history of seizures obtained by questionnaire from members of 47,626 twin pairs included in the Mid-Atlantic (MATR), Danish (DTR) and Norwegian (NTR) Twin Registries was verified using medical records and detailed clinical and family interviews...... with a verified history of epilepsy, 21.5% reported other seizures but not epilepsy and 18.5% of verified Norwegian epilepsy cases reported no history of epilepsy themselves and were identified only through their co-twin. The results of this study indicate that the accuracy of self-reported epilepsy and febrile...

Down syndrome screening in assisted conception twins: an iatrogenic medical challenge.

Science.gov (United States)

Ben-Ami, Ido; Maymon, Ron; Svirsky, Ran; Cuckle, Howard; Jauniaux, Eric

2013-11-01

The objective of this study was to provide a critical analysis of the impact of assisted conception on prenatal screening for Down syndrome (DS) in twin pregnancies and the value of various screening modalities for early detection of anomalies. The literature was searched using PubMed and the Cochrane Library focusing on prenatal screening and antenatal care of assisted-conception twin pregnancies. Serum screening alone is of limited value in detecting aneuploid twins, because the unaffected cotwin can "mask" the abnormal serum results of an affected one. In addition, this test can designate the pregnancy as at high risk but not identify the affected fetus. Nuchal translucency (NT) screening is the best available modality and a highly effective screening method for twin pregnancies. Among twins, NT alone has a 69% DS detection rate, first-trimester combined NT and serum biochemistry has a 72% DS detection rate, and an integrated screen will have an 80% DS detection rate at a 5% FPR. The data in the literature concerning the effect of assisted conception on maternal serum screening markers in twin pregnancies are scarce. Down syndrome screening in assisted-conception twins presents clinical and technical challenges. Therefore, assisted-conception twins need close monitoring from conception to delivery, by a practitioner familiar with the available screening modalities and their relative accuracy.

Level of anxiety in parents of high-risk premature twins.

Science.gov (United States)

Zanardo, V; Freato, F; Cereda, C

1998-01-01

We attempted to define parental anxiety in a population of parents of high-risk premature twins (mean birth weight 1,493 +/- 227 kg; mean gestational age 33 +/- 3.5 weeks), admitted to III level NICU. We specifically examined the following factors; gestational age of the twins, whether or not the twins had ventilatory support, pulmonary sequelae, major malformations or intra-ventricular hemorrhage, parental gender and highest level of education obtained by the parent. In the immediate pre-discharge period and a month later, a questionnaire (State-Trait Anxiety Inventory) was given to all parents of premature twins presenting for the discharge. The parents of 30 twins entered the study twice, at the discharge of their first twin (mean postnatal age 40 +/- 32 days), and one month later. They included 15 mothers and 11 fathers, aged 33 +/- 5.5 and 33 +/- 4.2 years, and at the second evaluation 11 mothers and 10 fathers, respectively. As case-controls we examined parental anxiety of fifteen consecutive singleton high-risk prematures, with equal gestational age, discharged immediately after. Our results indicate that the parents of high-risk twin and singleton prematures present an elevated, lasting state-trait anxiety level. Pre- and post-discharge parental anxiety is more elevated (not significant) in twinning with respect to the prematurity alone. When assessed separately by parental gender, in both these groups an increased (not significant) anxiety was persistently found in the mothers. We recommend that, although neonatologists generally define the discharge of the high-risk premature based upon the acquired stabilization of vital parameters, they pay special attention to the twin group we have identified which is at increased risk for predischarge parental anxiety.

Fetal growth disorders in twin gestations.

LENUS (Irish Health Repository)

Breathnach, Fionnuala M

2012-06-01

Twin growth is frequently mismatched. This review serves to explore the pathophysiologic mechanisms that underlie growth aberrations in twin gestations, the prenatal recognition of abnormal twin growth, and the critical importance of stratifying management of abnormal twin growth by chorionicity. Although poor in utero growth of both twins may reflect maternal factors resulting in global uteroplacental dysfunction, discordant twin growth may be attributed to differences in genetic potential between co-twins, placental dysfunction confined to one placenta only, or one placental territory within a shared placenta. In addition, twin-twin transfusion syndrome represents a distinct entity of which discordant growth is a common feature. Discordant growth is recognized as an independent risk factor for adverse perinatal outcome. Intertwin birth weight disparity of 18% or more should be considered to represent a discordance threshold, which serves as an independent risk factor for adverse perinatal outcome. At this cutoff, perinatal morbidity is found to increase both for the larger and the smaller twin within a discordant pair. There remains uncertainty surrounding the sonographic parameters that are most predictive of discordance. Although heightening of fetal surveillance in the face of discordant twin growth follows the principles applied to singleton gestations complicated by fetal growth restriction, the timing of intervention is largely influenced by chorionicity.

Nuchal translucency measurements are highly correlated in both mono- and dichorionic twin pairs

DEFF Research Database (Denmark)

Wøjdemann, Karen R; Larsen, Severin Olesen; Shalmi, Anne-Cathrine

2006-01-01

OBJECTIVES: To establish the distribution of serological and ultrasound first-trimester Down syndrome markers in twins and identify correlations of significance for risk calculation. METHODS: Nuchal translucency (NT), PAPP-A and betahCG data were extracted from 181 twin pregnancies (31 mono- and ...

Analyses of germline variants associated with ovarian cancer survival identify functional candidates at the 1q22 and 19p12 outcome loci

DEFF Research Database (Denmark)

Glubb, Dylan M; Johnatty, Sharon E; Quinn, Michael C J

2017-01-01

We previously identified associations with ovarian cancer outcome at five genetic loci. To identify putatively causal genetic variants and target genes, we prioritized two ovarian outcome loci (1q22 and 19p12) for further study. Bioinformatic and functional genetic analyses indicated that MEF2D...... and ZNF100 are targets of candidate outcome variants at 1q22 and 19p12, respectively. At 19p12, the chromatin interaction of a putative regulatory element with the ZNF100 promoter region correlated with candidate outcome variants. At 1q22, putative regulatory elements enhanced MEF2D promoter activity...... and haplotypes containing candidate outcome variants modulated these effects. In a public dataset, MEF2D and ZNF100 expression were both associated with ovarian cancer progression-free or overall survival time. In an extended set of 6,162 epithelial ovarian cancer patients, we found that functional candidates...

Neonatal status of twins

Directory of Open Access Journals (Sweden)

Božinović Dragica

2012-01-01

Full Text Available Multiple pregnancy is a pregnancy where more than one fetus develops simultaneously in the womb, as a result of the ovulation and fertilization of more than one egg. It is relatively rare in humans and represents the rest of the phylogenetic stages. The most common are twins and they indicate the development of two fetuses in the womb. The frequency of twin pregnancies is about 1%. Multiple pregnancies belong to a group of high-risk pregnancies because of the many complications that occur during the pregnancy: higher number of premature deliveries, bleeding, early neonatal complications and higher perinatal morbidity and mortality. Such pregnancies and infants require greater supervision and monitoring. The aim of this study was to determine the percentage of baby twins born at the maternity ward of the General Hospital in Prokuplje and their morbidity and mortality. Data on the total number of deliveries, number of twins, parity and maternal age, gestational age, body weight of twins, method of delivery, Apgar score and perinatal mortality were collected and statistically analyzed by means of retrospective analysis of operative birth and neonatal protocol for 6 years (2005 of 2010. Out of 4527 mothers who gave birth 43 were pairs of twins, or 0.95% of women gave birth to twins. These babies are more likely born by Caesarean section, but delivered with slightly lower birth weight.

Cohort Profile : The National Academy of Sciences-National Research Council Twin Registry (NAS-NRC Twin Registry)

NARCIS (Netherlands)

Gatz, Margaret; Harris, Jennifer R.; Kaprio, Jaakko; McGue, Matt; Smith, Nicholas L.; Snieder, Harold; Spiro, Avron; Butler, David A.

The National Academy of Sciences-National Research Council Twin Registry (NAS-NRC Twin Registry) is a comprehensive registry of White male twin pairs born in the USA between 1917 and 1927, both of the twins having served in the military. The purpose was medical research and ultimately improved

The role of data fusion in predictive maintenance using digital twin

Science.gov (United States)

Liu, Zheng; Meyendorf, Norbert; Mrad, Nezih

2018-04-01

Modern aerospace industry is migrating from reactive to proactive and predictive maintenance to increase platform operational availability and efficiency, extend its useful life cycle and reduce its life cycle cost. Multiphysics modeling together with data-driven analytics generate a new paradigm called "Digital Twin." The digital twin is actually a living model of the physical asset or system, which continually adapts to operational changes based on the collected online data and information, and can forecast the future of the corresponding physical counterpart. This paper reviews the overall framework to develop a digital twin coupled with the industrial Internet of Things technology to advance aerospace platforms autonomy. Data fusion techniques particularly play a significant role in the digital twin framework. The flow of information from raw data to high-level decision making is propelled by sensor-to-sensor, sensor-to-model, and model-to-model fusion. This paper further discusses and identifies the role of data fusion in the digital twin framework for aircraft predictive maintenance.

The UK10K project identifies rare variants in health and disease

DEFF Research Database (Denmark)

Walter, Klaudia; Min, Josine L.; Huang, Jie

2015-01-01

-marker and rare variant aggregation tests. We describe population structure and functional annotation of rare and low-frequency variants, use the data to estimate the benefits of sequencing for association studies, and summarize lessons from disease-specific collections. Finally, we make available an extensive...

Monozygotic twins with discordant intestinal rotation

International Nuclear Information System (INIS)

Smith, Vance L.; Nwomeh, Benedict C.; Long, Frederick

2006-01-01

Previous case reports have suggested a strong concordance of intestinal malrotation among identical twins. This has led to the recommendation that the asymptomatic twin undergo screening when malrotation is discovered in the identical sibling. We present a case of monozygotic twins in which one twin presented with intestinal malrotation with midgut volvulus while the other twin was found to have normal gastrointestinal anatomy. (orig.)

Monozygotic twins with discordant intestinal rotation

Energy Technology Data Exchange (ETDEWEB)

Smith, Vance L.; Nwomeh, Benedict C. [Ohio State University College of Medicine and Public Health, Department of Pediatric Surgery, Columbus Children' s Hospital, Columbus, OH (United States); Long, Frederick [Ohio State University College of Medicine and Public Health, Department of Radiology, Columbus Children' s Hospital, Columbus, OH (United States)

2006-04-15

Previous case reports have suggested a strong concordance of intestinal malrotation among identical twins. This has led to the recommendation that the asymptomatic twin undergo screening when malrotation is discovered in the identical sibling. We present a case of monozygotic twins in which one twin presented with intestinal malrotation with midgut volvulus while the other twin was found to have normal gastrointestinal anatomy. (orig.)

A Computational Discriminability Analysis on Twin Fingerprints

Science.gov (United States)

Liu, Yu; Srihari, Sargur N.

Sharing similar genetic traits makes the investigation of twins an important study in forensics and biometrics. Fingerprints are one of the most commonly found types of forensic evidence. The similarity between twins’ prints is critical establish to the reliability of fingerprint identification. We present a quantitative analysis of the discriminability of twin fingerprints on a new data set (227 pairs of identical twins and fraternal twins) recently collected from a twin population using both level 1 and level 2 features. Although the patterns of minutiae among twins are more similar than in the general population, the similarity of fingerprints of twins is significantly different from that between genuine prints of the same finger. Twins fingerprints are discriminable with a 1.5%~1.7% higher EER than non-twins. And identical twins can be distinguished by examine fingerprint with a slightly higher error rate than fraternal twins.

The utility of twins in developmental cognitive neuroscience research: How twins strengthen the ABCD research design.

Science.gov (United States)

Iacono, William G; Heath, Andrew C; Hewitt, John K; Neale, Michael C; Banich, Marie T; Luciana, Monica M; Madden, Pamela A; Barch, Deanna M; Bjork, James M

2018-08-01

The ABCD twin study will elucidate the genetic and environmental contributions to a wide range of mental and physical health outcomes in children, including substance use, brain and behavioral development, and their interrelationship. Comparisons within and between monozygotic and dizygotic twin pairs, further powered by multiple assessments, provide information about genetic and environmental contributions to developmental associations, and enable stronger tests of causal hypotheses, than do comparisons involving unrelated children. Thus a sub-study of 800 pairs of same-sex twins was embedded within the overall Adolescent Brain and Cognitive Development (ABCD) design. The ABCD Twin Hub comprises four leading centers for twin research in Minnesota, Colorado, Virginia, and Missouri. Each site is enrolling 200 twin pairs, as well as singletons. The twins are recruited from registries of all twin births in each State during 2006-2008. Singletons at each site are recruited following the same school-based procedures as the rest of the ABCD study. This paper describes the background and rationale for the ABCD twin study, the ascertainment of twin pairs and implementation strategy at each site, and the details of the proposed analytic strategies to quantify genetic and environmental influences and test hypotheses critical to the aims of the ABCD study. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Conjoined (Siamese) Twins in Zambia

African Journals Online (AJOL)

year-old Zambian multiparous mother gave birth to a set of twins with two heads ... (symmetric or mirror image) but one twin attached with an incomplete foetus is known as hetropagtrs. (asymmetrical). Thoracopagus twins (joined at the chest).

Ferrobielastic twinning in irradiated quartz

International Nuclear Information System (INIS)

Shiau, S.M.

1986-01-01

Cultured quartz is usually free from electrical twinning; however, it may occur if the seed crystal is twinned or if undue applied forces are exerted on the crystal. Ferrobielastic twinning was studied optically (photoelastic effect) and electrically (piezoelectric effect). At room temperature, twins were perceptible at stresses of about 2.l5 x 10 8 N/m 2 , and crystals switched from their original states to the alternative twin states at stresses about 5.0 x 10 8 N/m 2 (called coercive stress). The decrease in coercive stress with increasing temperature was observed, and these coercive stresses become very low as temperatures reach to 300 0 C. The effects of irradiation on the twinning in quartz were also studied. The presence of defects produced by irradiation was utilized to pin the domain wall motion. Both neutrons and gamma rays were employed. The stress required to nucleate an appreciable volume of twins is about twice as high for irradiated crystals than for those unirradiated. This result demonstrated that the irradiated crystals can tolerate higher stresses. However, the coercive stress for complete switch-over was not much different for irradiated and unirradiated crystals. It appears that the defects caused by irradiation eliminate the initial twinning events but do not affect switch-over

Voice similarity in identical twins.

Science.gov (United States)

Van Gysel, W D; Vercammen, J; Debruyne, F

2001-01-01

If people are asked to discriminate visually the two individuals of a monozygotic twin (MT), they mostly get into trouble. Does this problem also exist when listening to twin voices? Twenty female and 10 male MT voices were randomly assembled with one "strange" voice to get voice trios. The listeners (10 female students in Speech and Language Pathology) were asked to label the twins (voices 1-2, 1-3 or 2-3) in two conditions: two standard sentences read aloud and a 2.5-second midsection of a sustained /a/. The proportion correctly labelled twins was for female voices 82% and 63% and for male voices 74% and 52% for the sentences and the sustained /a/ respectively, both being significantly greater than chance (33%). The acoustic analysis revealed a high intra-twin correlation for the speaking fundamental frequency (SFF) of the sentences and the fundamental frequency (F0) of the sustained /a/. So the voice pitch could have been a useful characteristic in the perceptual identification of the twins. We conclude that there is a greater perceptual resemblance between the voices of identical twins than between voices without genetic relationship. The identification however is not perfect. The voice pitch possibly contributes to the correct twin identifications.

High-density genotyping of immune-related loci identifies new SLE risk variants in individuals with Asian ancestry.

Science.gov (United States)

Sun, Celi; Molineros, Julio E; Looger, Loren L; Zhou, Xu-Jie; Kim, Kwangwoo; Okada, Yukinori; Ma, Jianyang; Qi, Yuan-Yuan; Kim-Howard, Xana; Motghare, Prasenjeet; Bhattarai, Krishna; Adler, Adam; Bang, So-Young; Lee, Hye-Soon; Kim, Tae-Hwan; Kang, Young Mo; Suh, Chang-Hee; Chung, Won Tae; Park, Yong-Beom; Choe, Jung-Yoon; Shim, Seung Cheol; Kochi, Yuta; Suzuki, Akari; Kubo, Michiaki; Sumida, Takayuki; Yamamoto, Kazuhiko; Lee, Shin-Seok; Kim, Young Jin; Han, Bok-Ghee; Dozmorov, Mikhail; Kaufman, Kenneth M; Wren, Jonathan D; Harley, John B; Shen, Nan; Chua, Kek Heng; Zhang, Hong; Bae, Sang-Cheol; Nath, Swapan K

2016-03-01

Systemic lupus erythematosus (SLE) has a strong but incompletely understood genetic architecture. We conducted an association study with replication in 4,478 SLE cases and 12,656 controls from six East Asian cohorts to identify new SLE susceptibility loci and better localize known loci. We identified ten new loci and confirmed 20 known loci with genome-wide significance. Among the new loci, the most significant locus was GTF2IRD1-GTF2I at 7q11.23 (rs73366469, Pmeta = 3.75 × 10(-117), odds ratio (OR) = 2.38), followed by DEF6, IL12B, TCF7, TERT, CD226, PCNXL3, RASGRP1, SYNGR1 and SIGLEC6. We identified the most likely functional variants at each locus by analyzing epigenetic marks and gene expression data. Ten candidate variants are known to alter gene expression in cis or in trans. Enrichment analysis highlights the importance of these loci in B cell and T cell biology. The new loci, together with previously known loci, increase the explained heritability of SLE to 24%. The new loci share functional and ontological characteristics with previously reported loci and are possible drug targets for SLE therapeutics.

Growth curves for twins in Slovenia.

Science.gov (United States)

Bricelj, Katja; Blickstein, Isaac; Bržan-Šimenc, Gabrijela; Janša, Vid; Lučovnik, Miha; Verdenik, Ivan; Trojner-Bregar, Andreja; Tul, Nataša

2017-02-01

Abnormalities of fetal growth are more common in twins. We introduce the growth curves for monitoring fetal growth in twin pregnancies in Slovenia. Slovenian National Perinatal Information System for the period between 2002 and 2010 was used to calculate birth weight percentiles for all live born twins for each week from 22nd to 40th week. The calculated percentiles of birth weight for all live-born twins in Slovenia served as the basis for drawing 'growth' curves. The calculated growth curves for twins will help accurately diagnose small or large twin fetuses for their gestational age in the native central European population.

Deformation twinning: Influence of strain rate

Energy Technology Data Exchange (ETDEWEB)

Gray, G.T. III

1993-11-01

Twins in most crystal structures, including advanced materials such as intermetallics, form more readily as the temperature of deformation is decreased or the rate of deformation is increased. Both parameters lead to the suppression of thermally-activated dislocation processes which can result in stresses high enough to nucleate and grow deformation twins. Under high-strain rate or shock-loading/impact conditions deformation twinning is observed to be promoted even in high stacking fault energy FCC metals and alloys, composites, and ordered intermetallics which normally do not readily deform via twinning. Under such conditions and in particular under the extreme loading rates typical of shock wave deformation the competition between slip and deformation twinning can be examined in detail. In this paper, examples of deformation twinning in the intermetallics TiAl, Ti-48Al-lV and Ni{sub 3}A as well in the cermet Al-B{sub 4}C as a function of strain rate will be presented. Discussion includes: (1) the microstructural and experimental variables influencing twin formation in these systems and twinning topics related to high-strain-rate loading, (2) the high velocity of twin formation, and (3) the influence of deformation twinning on the constitutive response of advanced materials.

Fingerprint recognition with identical twin fingerprints.

Science.gov (United States)

Tao, Xunqiang; Chen, Xinjian; Yang, Xin; Tian, Jie

2012-01-01

Fingerprint recognition with identical twins is a challenging task due to the closest genetics-based relationship existing in the identical twins. Several pioneers have analyzed the similarity between twins' fingerprints. In this work we continue to investigate the topic of the similarity of identical twin fingerprints. Our study was tested based on a large identical twin fingerprint database that contains 83 twin pairs, 4 fingers per individual and six impressions per finger: 3984 (83*2*4*6) images. Compared to the previous work, our contributions are summarized as follows: (1) Two state-of-the-art fingerprint identification methods: P071 and VeriFinger 6.1 were used, rather than one fingerprint identification method in previous studies. (2) Six impressions per finger were captured, rather than just one impression, which makes the genuine distribution of matching scores more realistic. (3) A larger sample (83 pairs) was collected. (4) A novel statistical analysis, which aims at showing the probability distribution of the fingerprint types for the corresponding fingers of identical twins which have same fingerprint type, has been conducted. (5) A novel analysis, which aims at showing which finger from identical twins has higher probability of having same fingerprint type, has been conducted. Our results showed that: (a) A state-of-the-art automatic fingerprint verification system can distinguish identical twins without drastic degradation in performance. (b) The chance that the fingerprints have the same type from identical twins is 0.7440, comparing to 0.3215 from non-identical twins. (c) For the corresponding fingers of identical twins which have same fingerprint type, the probability distribution of five major fingerprint types is similar to the probability distribution for all the fingers' fingerprint type. (d) For each of four fingers of identical twins, the probability of having same fingerprint type is similar.

Fingerprint recognition with identical twin fingerprints.

Directory of Open Access Journals (Sweden)

Xunqiang Tao

Full Text Available Fingerprint recognition with identical twins is a challenging task due to the closest genetics-based relationship existing in the identical twins. Several pioneers have analyzed the similarity between twins' fingerprints. In this work we continue to investigate the topic of the similarity of identical twin fingerprints. Our study was tested based on a large identical twin fingerprint database that contains 83 twin pairs, 4 fingers per individual and six impressions per finger: 3984 (83*2*4*6 images. Compared to the previous work, our contributions are summarized as follows: (1 Two state-of-the-art fingerprint identification methods: P071 and VeriFinger 6.1 were used, rather than one fingerprint identification method in previous studies. (2 Six impressions per finger were captured, rather than just one impression, which makes the genuine distribution of matching scores more realistic. (3 A larger sample (83 pairs was collected. (4 A novel statistical analysis, which aims at showing the probability distribution of the fingerprint types for the corresponding fingers of identical twins which have same fingerprint type, has been conducted. (5 A novel analysis, which aims at showing which finger from identical twins has higher probability of having same fingerprint type, has been conducted. Our results showed that: (a A state-of-the-art automatic fingerprint verification system can distinguish identical twins without drastic degradation in performance. (b The chance that the fingerprints have the same type from identical twins is 0.7440, comparing to 0.3215 from non-identical twins. (c For the corresponding fingers of identical twins which have same fingerprint type, the probability distribution of five major fingerprint types is similar to the probability distribution for all the fingers' fingerprint type. (d For each of four fingers of identical twins, the probability of having same fingerprint type is similar.

The classical twin study and beyond

NARCIS (Netherlands)

Boomsma, D.I.; Busjahn, A.; Peltonen, L.

2002-01-01

Twin studies have been a valuable source of information about the genetic basis of complex traits. To maximize the potential of twin studies, large, worldwide registers of data on twins and their relatives have been established. Here, we provide an overview of the current resources for twin

Methylomic analysis of monozygotic twins discordant for autism spectrum disorder and related behavioural traits.

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Wong, C C Y; Meaburn, E L; Ronald, A; Price, T S; Jeffries, A R; Schalkwyk, L C; Plomin, R; Mill, J

2014-04-01

Autism spectrum disorder (ASD) defines a group of common, complex neurodevelopmental disorders. Although the aetiology of ASD has a strong genetic component, there is considerable monozygotic (MZ) twin discordance indicating a role for non-genetic factors. Because MZ twins share an identical DNA sequence, disease-discordant MZ twin pairs provide an ideal model for examining the contribution of environmentally driven epigenetic factors in disease. We performed a genome-wide analysis of DNA methylation in a sample of 50 MZ twin pairs (100 individuals) sampled from a representative population cohort that included twins discordant and concordant for ASD, ASD-associated traits and no autistic phenotype. Within-twin and between-group analyses identified numerous differentially methylated regions associated with ASD. In addition, we report significant correlations between DNA methylation and quantitatively measured autistic trait scores across our sample cohort. This study represents the first systematic epigenomic analyses of MZ twins discordant for ASD and implicates a role for altered DNA methylation in autism.

Genetic screens to identify pathogenic gene variants in the common cancer predisposition Lynch syndrome

DEFF Research Database (Denmark)

Drost, Mark; Lützen, Anne; van Hees, Sandrine

2013-01-01

In many individuals suspected of the common cancer predisposition Lynch syndrome, variants of unclear significance (VUS), rather than an obviously pathogenic mutations, are identified in one of the DNA mismatch repair (MMR) genes. The uncertainty of whether such VUS inactivate MMR, and therefore...... function. When a residue identified as mutated in an individual suspected of Lynch syndrome is listed as critical in such a reverse diagnosis catalog, there is a high probability that the corresponding human VUS is pathogenic. To investigate the applicability of this approach, we have generated....... Nearly half of these critical residues match with VUS previously identified in individuals suspected of Lynch syndrome. This aids in the assignment of pathogenicity to these human VUS and validates the approach described here as a diagnostic tool. In a wider perspective, this work provides a model...

Virtual Whipple: preoperative surgical planning with volume-rendered MDCT images to identify arterial variants relevant to the Whipple procedure.

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Brennan, Darren D; Zamboni, Giulia; Sosna, Jacob; Callery, Mark P; Vollmer, Charles M V; Raptopoulos, Vassilios D; Kruskal, Jonathan B

2007-05-01

The purposes of this study were to combine a thorough understanding of the technical aspects of the Whipple procedure with advanced rendering techniques by introducing a virtual Whipple procedure and to evaluate the utility of this new rendering technique in prediction of the arterial variants that cross the anticipated surgical resection plane. The virtual Whipple is a novel technique that follows the complex surgical steps in a Whipple procedure. Three-dimensional reconstructed angiographic images are used to identify arterial variants for the surgeon as part of the preoperative radiologic assessment of pancreatic and ampullary tumors.

Exotic quarks in Twin Higgs models

Energy Technology Data Exchange (ETDEWEB)

Cheng, Hsin-Chia [Department of Physics, University of California, Davis,One Shields Avenue, Davis, CA 95616 (United States); Jung, Sunghoon [School of Physics, Korea Institute for Advanced Study,85 Hoegiro, Dongdaemun-gu, Seoul 130-722 (Korea, Republic of); SLAC National Accelerator Laboratory,2575 Sand Hill Road, Menlo Park, CA 94025 (United States); Salvioni, Ennio [Department of Physics, University of California, Davis,One Shields Avenue, Davis, CA 95616 (United States); Tsai, Yuhsin [Department of Physics, University of California, Davis,One Shields Avenue, Davis, CA 95616 (United States); Maryland Center for Fundamental Physics,Department of Physics, University of Maryland,College Park, MD 20742 (United States)

2016-03-14

The Twin Higgs model provides a natural theory for the electroweak symmetry breaking without the need of new particles carrying the standard model gauge charges below a few TeV. In the low energy theory, the only probe comes from the mixing of the Higgs fields in the standard model and twin sectors. However, an ultraviolet completion is required below ∼ 10 TeV to remove residual logarithmic divergences. In non-supersymmetric completions, new exotic fermions charged under both the standard model and twin gauge symmetries have to be present to accompany the top quark, thus providing a high energy probe of the model. Some of them carry standard model color, and may therefore be copiously produced at current or future hadron colliders. Once produced, these exotic quarks can decay into a top together with twin sector particles. If the twin sector particles escape the detection, we have the irreducible stop-like signals. On the other hand, some twin sector particles may decay back into the standard model particles with long lifetimes, giving spectacular displaced vertex signals in combination with the prompt top quarks. This happens in the Fraternal Twin Higgs scenario with typical parameters, and sometimes is even necessary for cosmological reasons. We study the potential displaced vertex signals from the decays of the twin bottomonia, twin glueballs, and twin leptons in the Fraternal Twin Higgs scenario. Depending on the details of the twin sector, the exotic quarks may be probed up to ∼ 2.5 TeV at the LHC and beyond 10 TeV at a future 100 TeV collider, providing a strong test of this class of ultraviolet completions.

Twin Higgs Asymmetric Dark Matter.

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García García, Isabel; Lasenby, Robert; March-Russell, John

2015-09-18

We study asymmetric dark matter (ADM) in the context of the minimal (fraternal) twin Higgs solution to the little hierarchy problem, with a twin sector with gauged SU(3)^{'}×SU(2)^{'}, a twin Higgs doublet, and only third-generation twin fermions. Naturalness requires the QCD^{'} scale Λ_{QCD}^{'}≃0.5-20  GeV, and that t^{'} is heavy. We focus on the light b^{'} quark regime, m_{b^{'}}≲Λ_{QCD}^{'}, where QCD^{'} is characterized by a single scale Λ_{QCD}^{'} with no light pions. A twin baryon number asymmetry leads to a successful dark matter (DM) candidate: the spin-3/2 twin baryon, Δ^{'}∼b^{'}b^{'}b^{'}, with a dynamically determined mass (∼5Λ_{QCD}^{'}) in the preferred range for the DM-to-baryon ratio Ω_{DM}/Ω_{baryon}≃5. Gauging the U(1)^{'} group leads to twin atoms (Δ^{'}-τ^{'}[over ¯] bound states) that are successful ADM candidates in significant regions of parameter space, sometimes with observable changes to DM halo properties. Direct detection signatures satisfy current bounds, at times modified by dark form factors.

Fine-Scale Mapping at 9p22.2 Identifies Candidate Causal Variants That Modify Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers.

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Elena Vigorito

Full Text Available Population-based genome wide association studies have identified a locus at 9p22.2 associated with ovarian cancer risk, which also modifies ovarian cancer risk in BRCA1 and BRCA2 mutation carriers. We conducted fine-scale mapping at 9p22.2 to identify potential causal variants in BRCA1 and BRCA2 mutation carriers. Genotype data were available for 15,252 (2,462 ovarian cancer cases BRCA1 and 8,211 (631 ovarian cancer cases BRCA2 mutation carriers. Following genotype imputation, ovarian cancer associations were assessed for 4,873 and 5,020 SNPs in BRCA1 and BRCA 2 mutation carriers respectively, within a retrospective cohort analytical framework. In BRCA1 mutation carriers one set of eight correlated candidate causal variants for ovarian cancer risk modification was identified (top SNP rs10124837, HR: 0.73, 95%CI: 0.68 to 0.79, p-value 2× 10-16. These variants were located up to 20 kb upstream of BNC2. In BRCA2 mutation carriers one region, up to 45 kb upstream of BNC2, and containing 100 correlated SNPs was identified as candidate causal (top SNP rs62543585, HR: 0.69, 95%CI: 0.59 to 0.80, p-value 1.0 × 10-6. The candidate causal in BRCA1 mutation carriers did not include the strongest associated variant at this locus in the general population. In sum, we identified a set of candidate causal variants in a region that encompasses the BNC2 transcription start site. The ovarian cancer association at 9p22.2 may be mediated by different variants in BRCA1 mutation carriers and in the general population. Thus, potentially different mechanisms may underlie ovarian cancer risk for mutation carriers and the general population.

Pulmonary function in advanced uncomplicated singleton and twin pregnancy.

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Siddiqui, Anwar Hasan; Tauheed, Nazia; Ahmad, Aquil; Mohsin, Zehra

2014-01-01

Pregnancy brings about significant changes in respiratory function, as evidenced by alterations in lung volumes and capacities, which are attributable to the mechanical impediment caused by the growing foetus. This study was undertaken in order to identify changes in respiratory function during normal pregnancy and to determine whether such changes are more pronounced in twin pregnancy than in singleton pregnancy. Respiratory function was assessed in 50 women with twin pregnancies and in 50 women with singleton pregnancies (during the third trimester in both groups), as well as in 50 non-pregnant women. We measured the following pulmonary function test parameters: FVC; FEV1; PEF rate; FEV1/FVC ratio; FEF25-75%; and maximal voluntary ventilation. All respiratory parameters except the FEV1/FVC ratio were found to be lower in the pregnant women than in the non-pregnant women. We found no significant differences between women with twin pregnancies and those with singleton pregnancies, in terms of respiratory function. Despite its higher physiological demands, twin pregnancy does not appear to impair respiratory function to any greater degree than does singleton pregnancy.

Attachment to the Romantic Partner and Sibling: Attachment Hierarchies of Twins and Non-Twin Siblings

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Sascha Schwarz

2015-12-01

Full Text Available Previous studies have shown that romantic partners and siblings are important attachment figures. This study compares the attachment to the romantic partner with the attachment to the sibling as a function of the participant’s sibling type among monozygotic (MZ twins, dizygotic (DZ twins, and non-twin (NT siblings. The results show that MZ twins prefer their sibling to their romantic partner whereas DZ twins are equally attached to their sibling and romantic partner. In contrast, NT siblings are more attached to their romantic partner compared to their sibling. These results indicate that genetic relatedness has profound impact on a person’s attachment hierarchy and the relative rank of the romantic partner and the sibling.

Neurodevelopmental outcome at 2 years in twin-twin transfusion syndrome survivors randomized for the Solomon trial.

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van Klink, Jeanine M M; Slaghekke, Femke; Balestriero, Marina A; Scelsa, Barbara; Introvini, Paola; Rustico, Mariangela; Faiola, Stefano; Rijken, Monique; Koopman, Hendrik M; Middeldorp, Johanna M; Oepkes, Dick; Lopriore, Enrico

2016-01-01

The preferred treatment for twin-twin transfusion syndrome is fetoscopic laser coagulation of inter-twin vascular anastomoses on the monochorionic placenta. Severe postoperative complications can occur when inter-twin vascular anastomoses remain patent including twin-anemia polycythemia sequence or recurrent twin-twin transfusion syndrome. To minimize the occurrence of residual anastomoses, a modified laser surgery technique, the Solomon technique, was developed in which the entire vascular equator is coagulated. In the Solomon randomized controlled trial (NTR1245), the Solomon technique was associated with a significant reduction in twin-anemia polycythemia sequence and recurrence of twin-twin transfusion syndrome when compared with the standard laser surgery technique. Although a significant improvement in perinatal outcome was shown after the Solomon technique, the clinical importance should also be ascertained with long-term follow-up evaluation of the surviving children. The purpose of this study was to compare the long-term neurodevelopmental outcome in surviving children with twin-twin transfusion syndrome who were included in the Solomon randomized trial and treated with either the Solomon technique or standard laser surgery technique. Routine standardized follow-up evaluation in survivors, at least 2 years after the estimated date of delivery, was performed at 2 of the 5 centers that participated in the Solomon trial: Buzzi Hospital Milan (Italy) and Leiden University Medical Center (The Netherlands). The primary outcome of this follow-up study was survival without long-term neurodevelopmental impairment at age 2 years. Neurodevelopmental impairment was defined as cerebral palsy, cognitive and/or motor development score of neurodevelopmental impairment) was detected in 95 of 141 cases (67%) in the Solomon group and in 99 of 146 cases (68%) in the standard group (P = .92). Neurodevelopmental impairment in long-term survivors who were included for follow

Sequencing of sporadic Attention-Deficit Hyperactivity Disorder (ADHD) identifies novel and potentially pathogenic de novo variants and excludes overlap with genes associated with autism spectrum disorder.

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Kim, Daniel Seung; Burt, Amber A; Ranchalis, Jane E; Wilmot, Beth; Smith, Joshua D; Patterson, Karynne E; Coe, Bradley P; Li, Yatong K; Bamshad, Michael J; Nikolas, Molly; Eichler, Evan E; Swanson, James M; Nigg, Joel T; Nickerson, Deborah A; Jarvik, Gail P

2017-06-01

Attention-Deficit Hyperactivity Disorder (ADHD) has high heritability; however, studies of common variation account for ADHD variance. Using data from affected participants without a family history of ADHD, we sought to identify de novo variants that could account for sporadic ADHD. Considering a total of 128 families, two analyses were conducted in parallel: first, in 11 unaffected parent/affected proband trios (or quads with the addition of an unaffected sibling) we completed exome sequencing. Six de novo missense variants at highly conserved bases were identified and validated from four of the 11 families: the brain-expressed genes TBC1D9, DAGLA, QARS, CSMD2, TRPM2, and WDR83. Separately, in 117 unrelated probands with sporadic ADHD, we sequenced a panel of 26 genes implicated in intellectual disability (ID) and autism spectrum disorder (ASD) to evaluate whether variation in ASD/ID-associated genes were also present in participants with ADHD. Only one putative deleterious variant (Gln600STOP) in CHD1L was identified; this was found in a single proband. Notably, no other nonsense, splice, frameshift, or highly conserved missense variants in the 26 gene panel were identified and validated. These data suggest that de novo variant analysis in families with independently adjudicated sporadic ADHD diagnosis can identify novel genes implicated in ADHD pathogenesis. Moreover, that only one of the 128 cases (0.8%, 11 exome, and 117 MIP sequenced participants) had putative deleterious variants within our data in 26 genes related to ID and ASD suggests significant independence in the genetic pathogenesis of ADHD as compared to ASD and ID phenotypes. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Low twinning rate and seasonal effects on twinning in a fertile population, the Hutterites

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Nonaka, K.; Miura, T.; Peter, K.

1993-09-01

This paper analyzes from the mid 18th century to 1987 the birth records of the “Dariusleut,” one of the three subgroups of the Hutterite population. The aim of this study is to describe several aspects of the twinning rate in a fertile population. The overall rate of twinning was 0.90%:103 twins among all 11492 maternities. The rate peaked at the 7th birth order and at the maternal age of 40 years and over. Until the mid 19th century when the Hutterites lived in Russia, the twinning rate was higher (1.5%), and it decreased during the migration period in the second half of the 19th century (0.7%). After the group had settled in the USA and Canada, the population maintained a twinning rate of 1.0% until 1965. After 1965 the rate decreased to 0.7%, partly due to a decline in fertility among women aged 30 years and over. There was a significant seasonal variation: the twinning rate decreased to 0.5% in May July compared to 1.2% for the other three seasons during the years up to 1965 ( P<0.01), while more recent mothers did not show such a seasonal variation. The incidence of twin births in this population seems to have been influenced by environmental factors, which would change their effect seasonally and secularly.

Systematic Functional Interrogation of Rare Cancer Variants Identifies Oncogenic Alleles | Office of Cancer Genomics

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Cancer genome characterization efforts now provide an initial view of the somatic alterations in primary tumors. However, most point mutations occur at low frequency, and the function of these alleles remains undefined. We have developed a scalable systematic approach to interrogate the function of cancer-associated gene variants. We subjected 474 mutant alleles curated from 5,338 tumors to pooled in vivo tumor formation assays and gene expression profiling. We identified 12 transforming alleles, including two in genes (PIK3CB, POT1) that have not been shown to be tumorigenic.

Case-control study for colorectal cancer genetic susceptibility in EPICOLON: previously identified variants and mucins

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Moreno Victor

2011-08-01

Full Text Available Abstract Background Colorectal cancer (CRC is the second leading cause of cancer death in developed countries. Familial aggregation in CRC is also important outside syndromic forms and, in this case, a polygenic model with several common low-penetrance alleles contributing to CRC genetic predisposition could be hypothesized. Mucins and GALNTs (N-acetylgalactosaminyltransferase are interesting candidates for CRC genetic susceptibility and have not been previously evaluated. We present results for ten genetic variants linked to CRC risk in previous studies (previously identified category and 18 selected variants from the mucin gene family in a case-control association study from the Spanish EPICOLON consortium. Methods CRC cases and matched controls were from EPICOLON, a prospective, multicenter, nationwide Spanish initiative, comprised of two independent stages. Stage 1 corresponded to 515 CRC cases and 515 controls, whereas stage 2 consisted of 901 CRC cases and 909 controls. Also, an independent cohort of 549 CRC cases and 599 controls outside EPICOLON was available for additional replication. Genotyping was performed for ten previously identified SNPs in ADH1C, APC, CCDN1, IL6, IL8, IRS1, MTHFR, PPARG, VDR and ARL11, and 18 selected variants in the mucin gene family. Results None of the 28 SNPs analyzed in our study was found to be associated with CRC risk. Although four SNPs were significant with a P-value ADH1C (OR = 1.63, 95% CI = 1.06-2.50, P-value = 0.02, recessive, rs1800795 in IL6 (OR = 1.62, 95% CI = 1.10-2.37, P-value = 0.01, recessive, rs3803185 in ARL11 (OR = 1.58, 95% CI = 1.17-2.15, P-value = 0.007, codominant, and rs2102302 in GALNTL2 (OR = 1.20, 95% CI = 1.00-1.44, P-value = 0.04, log-additive 0, 1, 2 alleles], only rs3803185 achieved statistical significance in EPICOLON stage 2 (OR = 1.34, 95% CI = 1.06-1.69, P-value = 0.01, recessive. In the joint analysis for both stages, results were only significant for rs3803185 (OR = 1

Case-control study for colorectal cancer genetic susceptibility in EPICOLON: previously identified variants and mucins

International Nuclear Information System (INIS)

Abulí, Anna; Morillas, Juan D; Rigau, Joaquim; Latorre, Mercedes; Fernández-Bañares, Fernando; Peña, Elena; Riestra, Sabino; Payá, Artemio; Jover, Rodrigo; Xicola, Rosa M; Llor, Xavier; Fernández-Rozadilla, Ceres; Carvajal-Carmona, Luis; Villanueva, Cristina M; Moreno, Victor; Piqué, Josep M; Carracedo, Angel; Castells, Antoni; Andreu, Montserrat; Ruiz-Ponte, Clara; Castellví-Bel, Sergi; Alonso-Espinaco, Virginia; Muñoz, Jenifer; Gonzalo, Victoria; Bessa, Xavier; González, Dolors; Clofent, Joan; Cubiella, Joaquin

2011-01-01

Colorectal cancer (CRC) is the second leading cause of cancer death in developed countries. Familial aggregation in CRC is also important outside syndromic forms and, in this case, a polygenic model with several common low-penetrance alleles contributing to CRC genetic predisposition could be hypothesized. Mucins and GALNTs (N-acetylgalactosaminyltransferase) are interesting candidates for CRC genetic susceptibility and have not been previously evaluated. We present results for ten genetic variants linked to CRC risk in previous studies (previously identified category) and 18 selected variants from the mucin gene family in a case-control association study from the Spanish EPICOLON consortium. CRC cases and matched controls were from EPICOLON, a prospective, multicenter, nationwide Spanish initiative, comprised of two independent stages. Stage 1 corresponded to 515 CRC cases and 515 controls, whereas stage 2 consisted of 901 CRC cases and 909 controls. Also, an independent cohort of 549 CRC cases and 599 controls outside EPICOLON was available for additional replication. Genotyping was performed for ten previously identified SNPs in ADH1C, APC, CCDN1, IL6, IL8, IRS1, MTHFR, PPARG, VDR and ARL11, and 18 selected variants in the mucin gene family. None of the 28 SNPs analyzed in our study was found to be associated with CRC risk. Although four SNPs were significant with a P-value < 0.05 in EPICOLON stage 1 [rs698 in ADH1C (OR = 1.63, 95% CI = 1.06-2.50, P-value = 0.02, recessive), rs1800795 in IL6 (OR = 1.62, 95% CI = 1.10-2.37, P-value = 0.01, recessive), rs3803185 in ARL11 (OR = 1.58, 95% CI = 1.17-2.15, P-value = 0.007, codominant), and rs2102302 in GALNTL2 (OR = 1.20, 95% CI = 1.00-1.44, P-value = 0.04, log-additive 0, 1, 2 alleles], only rs3803185 achieved statistical significance in EPICOLON stage 2 (OR = 1.34, 95% CI = 1.06-1.69, P-value = 0.01, recessive). In the joint analysis for both stages, results were only significant for rs3803185 (OR = 1.12, 95% CI = 1

Rs895819 in MIR27A improves the predictive value of DPYD variants to identify patients at risk of severe fluoropyrimidine-associated toxicity.

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Meulendijks, Didier; Henricks, Linda M; Amstutz, Ursula; Froehlich, Tanja K; Largiadèr, Carlo R; Beijnen, Jos H; de Boer, Anthonius; Deenen, Maarten J; Cats, Annemieke; Schellens, Jan H M

2016-06-01

The objective of this study was to determine whether genotyping of MIR27A polymorphisms rs895819A>G and rs11671784C>T can be used to improve the predictive value of DPYD variants to identify patients at risk of severe fluoropyrimidine-associated toxicity (FP-toxicity). Patients treated previously in a prospective study with fluoropyrimidine-based chemotherapy were genotyped for rs895819 and rs11671784, and DPYD c.2846A>T, c.1679T>G, c.1129-5923C>G and c.1601G>A. The predictive value of MIR27A variants for early-onset grade ≥3 FP-toxicity, alone or in combination with DPYD variants, was tested in multivariable logistic regression models. Random-effects meta-analysis was performed, including previously published data. A total of 1,592 patients were included. Allele frequencies of rs895819 and rs11671784 were 0.331 and 0.020, respectively. In DPYD wild-type patients, MIR27A variants did not affect risk of FP-toxicity (OR 1.3 for ≥1 variant MIR27A allele vs. none, 95% CI: 0.87-1.82, p = 0.228). In contrast, in patients carrying DPYD variants, the presence of ≥1 rs895819 variant allele was associated with increased risk of FP-toxicity (OR 4.9, 95% CI: 1.24-19.7, p = 0.023). Rs11671784 was not associated with FP-toxicity (OR 2.9, 95% CI: 0.47-18.0, p = 0.253). Patients carrying a DPYD variant and rs895819 were at increased risk of FP-toxicity compared to patients wild type for rs895819 and DPYD (OR 2.4, 95% CI: 1.27-4.37, p = 0.007), while patients with a DPYD variant but without a MIR27A variant were not (OR 0.3 95% CI: 0.06-1.17, p = 0.081). In meta-analysis, rs895819 remained significantly associated with FP-toxicity in DPYD variant allele carriers, OR 5.4 (95% CI: 1.83-15.7, p = 0.002). This study demonstrates the clinical validity of combined MIR27A/DPYD screening to identify patients at risk of severe FP-toxicity. © 2016 UICC.

Whole-exome sequencing identifies common and rare variant metabolic QTLs in a Middle Eastern population.

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Yousri, Noha A; Fakhro, Khalid A; Robay, Amal; Rodriguez-Flores, Juan L; Mohney, Robert P; Zeriri, Hassina; Odeh, Tala; Kader, Sara Abdul; Aldous, Eman K; Thareja, Gaurav; Kumar, Manish; Al-Shakaki, Alya; Chidiac, Omar M; Mohamoud, Yasmin A; Mezey, Jason G; Malek, Joel A; Crystal, Ronald G; Suhre, Karsten

2018-01-23

Metabolomics-genome-wide association studies (mGWAS) have uncovered many metabolic quantitative trait loci (mQTLs) influencing human metabolic individuality, though predominantly in European cohorts. By combining whole-exome sequencing with a high-resolution metabolomics profiling for a highly consanguineous Middle Eastern population, we discover 21 common variant and 12 functional rare variant mQTLs, of which 45% are novel altogether. We fine-map 10 common variant mQTLs to new metabolite ratio associations, and 11 common variant mQTLs to putative protein-altering variants. This is the first work to report common and rare variant mQTLs linked to diseases and/or pharmacological targets in a consanguineous Arab cohort, with wide implications for precision medicine in the Middle East.

Identifying Copy Number Variants under Selection in Geographically Structured Populations Based on -statistics

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Hae-Hiang Song

2012-06-01

Full Text Available Large-scale copy number variants (CNVs in the human provide the raw material for delineating population differences, as natural selection may have affected at least some of the CNVs thus far discovered. Although the examination of relatively large numbers of specific ethnic groups has recently started in regard to inter-ethnic group differences in CNVs, identifying and understanding particular instances of natural selection have not been performed. The traditional FST measure, obtained from differences in allele frequencies between populations, has been used to identify CNVs loci subject to geographically varying selection. Here, we review advances and the application of multinomial-Dirichlet likelihood methods of inference for identifying genome regions that have been subject to natural selection with the FST estimates. The contents of presentation are not new; however, this review clarifies how the application of the methods to CNV data, which remains largely unexplored, is possible. A hierarchical Bayesian method, which is implemented via Markov Chain Monte Carlo, estimates locus-specific FST and can identify outlying CNVs loci with large values of FST. By applying this Bayesian method to the publicly available CNV data, we identified the CNV loci that show signals of natural selection, which may elucidate the genetic basis of human disease and diversity.

Risk Factors Associated with Preterm Delivery after Fetoscopic Laser Surgery for Twin Twin Transfusion Syndrome

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PAPANNA, Ramesha; BLOCK-ABRAHAM, Dana; Mann, Lovepreet K; BUHIMSCHI, Irina A.; BEBBINGTON, Michael; GARCIA, Elisa; KAHLEK, Nahla; HARMAN, Christopher; JOHNSON, Anthony; BASCHAT, Ahmet; MOISE, Kenneth J.

2014-01-01

OBJECTIVE Despite improved perinatal survival following fetoscopic laser surgery (FLS) for twin twin transfusion syndrome (TTTS), prematurity remains an important contributor to perinatal mortality and morbidity. The objective of the study was to identify risk factors for complicated preterm delivery after FLS. STUDY DESIGN Retrospective cohort study of prospectively collected data on maternal/fetal demographics and pre-operative, operative and post-operative variables of 459 patients treated in 3 U.S. fetal centers. Multivariate linear regression was performed to identify significant risk factors associated with preterm delivery, which was cross-validated using K-fold method. Multivariate logistic regression was performed to identify risk factors for early vs. late preterm delivery based on median gestational age at delivery of 32 weeks. RESULTS There were significant differences in case selection and outcomes between the centers. After controlling for the center of surgery, a multivariate analysis indicated a lower maternal age at procedure, history of previous prematurity, shortened cervical length, use of amnioinfusion, 12 Fr cannula diameter, lack of a collagen plug placement and iatrogenic preterm premature rupture of membranes (iPPROM) were significantly associated with a lower gestational age at delivery. CONCLUSION Specific fetal/maternal and operative variables are associated with preterm delivery after FLS for the treatment of TTTS. Further studies to modify some of these variables may decrease the perinatal morbidity after laser therapy. PMID:24013922

The effect of deformation twinning on stress localization in a three dimensional TWIP steel microstructure

International Nuclear Information System (INIS)

Tari, Vahid; Kadiri, Haitham El; Oppedal, Andrew L; King, Roger L; Rollett, Anthony D; Beladi, Hossein

2015-01-01

We present an investigation of the effect of deformation twinning on the visco-plastic response and stress localization in a low stacking fault energy twinning-induced plasticity (TWIP) steel under uniaxial tension loading. The three-dimensional full field response was simulated using the fast Fourier transform method. The initial microstructure was obtained from a three dimensional serial section using electron backscatter diffraction. Twin volume fraction evolution upon strain was measured so the hardening parameters of the simple Voce model could be identified to fit both the stress-strain behavior and twinning activity. General trends of texture evolution were acceptably predicted including the typical sharpening and balance between the 〈1 1 1〉 fiber and the 〈1 0 0〉 fiber. Twinning was found to nucleate preferentially at grain boundaries although the predominant twin reorientation scheme did not allow spatial propagation to be captured. Hot spots in stress correlated with the boundaries of twinned voxel domains, which either impeded or enhanced twinning based on which deformation modes were active locally. (paper)

Acardiac twin with externalized intestine adherent to placenta: unusual manifestation of omphalocele.

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Emery, Shawn Clark; Vaux, Keith K; Pretorius, Dolores; Masliah, Eliezer; Benirschke, Kurt

2004-01-01

TRAP (twin reversed arterial perfusion) syndrome produces an acardiac twin (acardiac monster, acardius, acardiacus, chorioangiopagus parasiticus, etc.). Acardiacs result from monozygotic multiple births in which three anatomic anomalies occur: (1) a fetus' cardiac development is disturbed; (2) artery-artery anastomosis carries blood from a normal ("pump") twin to the acardiac; (3) vein-vein anastomosis carries blood from the acardiac back to the normal twin. Whether reversal of blood flow in the acardiac results from or causes cardiac dysmorphogenesis has not been resolved. Acardiac twins demonstrate a complex constellation of malformations usually thought to result from reversed blood flow; omphalocele is particularly common. We report monochorionic monoamnionic male twins in which an acardiac twin demonstrated externalized intestines adherent to the placenta. The twins were delivered from a 30-year-old primigravida mother by cesarean section without maternal complications at 33 w. The mother has no significant past medical history. The macerated acardius had a 4-cm long attenuated umbilical cord with indeterminate number of vessels. Structures rostral to the thorax were absent save for one poorly developed hand and arm. The abdomen contained loose mesenchyme and no organs. The entire intestine (21 cm) along with two testes was located in a sac on the surface of the placenta. No histopathologic anomalies of formed structures were identified aside from spatial relationships and incomplete development. The normal twin required no intensive care and is doing well. To our knowledge, this is the first report of externalized intestine, which may represent an unusual consequence of omphalocele.

'Twin2twin' an innovative method of empowering midwives to strengthen their professional midwifery organisations.

Science.gov (United States)

Cadée, Franka; Perdok, Hilde; Sam, Betty; de Geus, Myrte; Kweekel, Liselotte

2013-10-01

midwives need professional support from a national midwifery organisation to be able to provide the services that are by regulatory mechanisms and accreditation expected of them. Not all midwives in the world are united in a professional organisation. The aim of this project was to strengthen the midwifery organisations of Sierra Leone and the Netherlands. During the process of the project it was realised that the development of a platform of exchange at organisational level would be enhanced by introducing personal exchange between individual midwives. In response to this new insight the original project plan was adjusted by incorporating the twin2twin method. twin2twin is a feminist methodology of mutual exchange between twenty pairs of midwives from different organisations (in this case Sierra Leone and the Netherlands). The method can be distinguished by 10 specific steps. It was developed, used and (re)evaluated through focus group discussions, storytelling and written evaluations. twinning of organisations was strengthened by adding a human component to the process. With the use of the 'twin2twin' method, midwives were encouraged to invested in a professional and personal bond with their 'twin sister'. This bond was independent and went beyond the relatively short four year project period. Through personal engagement and mutual exchange of knowledge and skills, midwives empowered each other to build and strengthen their midwifery organisations both in Sierra Leone and the Netherlands. (Empowerment refers to the expansion in people's ability to make strategic life choices in a context where this ability was previously denied to them (Narayan, 2005); organisational empowerment includes processes and structures that enhance members' skills and provides them with the mutual support necessary to effect community level change (Zimmerman, 1995).). despite challenges we are convinced that twin2twin can be of additional benefit for the success of other projects

Temporal expression profiling identifies pathways mediating effect of causal variant on phenotype.

Directory of Open Access Journals (Sweden)

Saumya Gupta

2015-06-01

Full Text Available Even with identification of multiple causal genetic variants for common human diseases, understanding the molecular processes mediating the causal variants' effect on the disease remains a challenge. This understanding is crucial for the development of therapeutic strategies to prevent and treat disease. While static profiling of gene expression is primarily used to get insights into the biological bases of diseases, it makes differentiating the causative from the correlative effects difficult, as the dynamics of the underlying biological processes are not monitored. Using yeast as a model, we studied genome-wide gene expression dynamics in the presence of a causal variant as the sole genetic determinant, and performed allele-specific functional validation to delineate the causal effects of the genetic variant on the phenotype. Here, we characterized the precise genetic effects of a functional MKT1 allelic variant in sporulation efficiency variation. A mathematical model describing meiotic landmark events and conditional activation of MKT1 expression during sporulation specified an early meiotic role of this variant. By analyzing the early meiotic genome-wide transcriptional response, we demonstrate an MKT1-dependent role of novel modulators, namely, RTG1/3, regulators of mitochondrial retrograde signaling, and DAL82, regulator of nitrogen starvation, in additively effecting sporulation efficiency. In the presence of functional MKT1 allele, better respiration during early sporulation was observed, which was dependent on the mitochondrial retrograde regulator, RTG3. Furthermore, our approach showed that MKT1 contributes to sporulation independent of Puf3, an RNA-binding protein that steady-state transcription profiling studies have suggested to mediate MKT1-pleiotropic effects during mitotic growth. These results uncover interesting regulatory links between meiosis and mitochondrial retrograde signaling. In this study, we highlight the advantage

Annotating pathogenic non-coding variants in genic regions.

Science.gov (United States)

Gelfman, Sahar; Wang, Quanli; McSweeney, K Melodi; Ren, Zhong; La Carpia, Francesca; Halvorsen, Matt; Schoch, Kelly; Ratzon, Fanni; Heinzen, Erin L; Boland, Michael J; Petrovski, Slavé; Goldstein, David B

2017-08-09

Identifying the underlying causes of disease requires accurate interpretation of genetic variants. Current methods ineffectively capture pathogenic non-coding variants in genic regions, resulting in overlooking synonymous and intronic variants when searching for disease risk. Here we present the Transcript-inferred Pathogenicity (TraP) score, which uses sequence context alterations to reliably identify non-coding variation that causes disease. High TraP scores single out extremely rare variants with lower minor allele frequencies than missense variants. TraP accurately distinguishes known pathogenic and benign variants in synonymous (AUC = 0.88) and intronic (AUC = 0.83) public datasets, dismissing benign variants with exceptionally high specificity. TraP analysis of 843 exomes from epilepsy family trios identifies synonymous variants in known epilepsy genes, thus pinpointing risk factors of disease from non-coding sequence data. TraP outperforms leading methods in identifying non-coding variants that are pathogenic and is therefore a valuable tool for use in gene discovery and the interpretation of personal genomes.While non-coding synonymous and intronic variants are often not under strong selective constraint, they can be pathogenic through affecting splicing or transcription. Here, the authors develop a score that uses sequence context alterations to predict pathogenicity of synonymous and non-coding genetic variants, and provide a web server of pre-computed scores.

Twin-spot laser welding of advanced high-strength multiphase microstructure steel

Science.gov (United States)

Grajcar, Adam; Morawiec, Mateusz; Różański, Maciej; Stano, Sebastian

2017-07-01

The study addresses the results concerning the laser welding of TRIP (TRansformation Induced Plasticity) steel using a beam focused at two spots (also referred to as twin-spot laser welding). The analysis involved the effect of variable welding thermal cycles on the properties and microstructure of welded joints. The tests were performed using a linear energy of 0.048 and 0.060 kJ/mm and the laser beam power distribution of 50%:50%, 60%:40% and 70%:30%. The tests also involved welding performed using a linear energy of 0.150 kJ/mm and the laser beam power distribution of 70%:30%. In addition, the research included observations of the microstructure of the fusion zone, heat affected zone and the transition zone using light microscopy and scanning electron microscopy. The fusion zone was composed of blocky-lath martensite whereas the HAZ (heat-affected zone) was characterised by the lath microstructure containing martensite, bainite and retained austenite. The distribution of twin-spot laser beam power significantly affected the microstructure and hardness profiles of welded joints. The highest hardness (480-505 HV), regardless of welding variants used, was observed in the HAZ.

Education in Twins and Their Parents Across Birth Cohorts Over 100 years: An Individual-Level Pooled Analysis of 42-Twin Cohorts.

Science.gov (United States)

Silventoinen, Karri; Jelenkovic, Aline; Latvala, Antti; Sund, Reijo; Yokoyama, Yoshie; Ullemar, Vilhelmina; Almqvist, Catarina; Derom, Catherine A; Vlietinck, Robert F; Loos, Ruth J F; Kandler, Christian; Honda, Chika; Inui, Fujio; Iwatani, Yoshinori; Watanabe, Mikio; Rebato, Esther; Stazi, Maria A; Fagnani, Corrado; Brescianini, Sonia; Hur, Yoon-Mi; Jeong, Hoe-Uk; Cutler, Tessa L; Hopper, John L; Busjahn, Andreas; Saudino, Kimberly J; Ji, Fuling; Ning, Feng; Pang, Zengchang; Rose, Richard J; Koskenvuo, Markku; Heikkilä, Kauko; Cozen, Wendy; Hwang, Amie E; Mack, Thomas M; Siribaddana, Sisira H; Hotopf, Matthew; Sumathipala, Athula; Rijsdijk, Fruhling; Sung, Joohon; Kim, Jina; Lee, Jooyeon; Lee, Sooji; Nelson, Tracy L; Whitfield, Keith E; Tan, Qihua; Zhang, Dongfeng; Llewellyn, Clare H; Fisher, Abigail; Burt, S Alexandra; Klump, Kelly L; Knafo-Noam, Ariel; Mankuta, David; Abramson, Lior; Medland, Sarah E; Martin, Nicholas G; Montgomery, Grant W; Magnusson, Patrik K E; Pedersen, Nancy L; Dahl Aslan, Anna K; Corley, Robin P; Huibregtse, Brooke M; Öncel, Sevgi Y; Aliev, Fazil; Krueger, Robert F; McGue, Matt; Pahlen, Shandell; Willemsen, Gonneke; Bartels, Meike; van Beijsterveldt, Catharina E M; Silberg, Judy L; Eaves, Lindon J; Maes, Hermine H; Harris, Jennifer R; Brandt, Ingunn; Nilsen, Thomas S; Rasmussen, Finn; Tynelius, Per; Baker, Laura A; Tuvblad, Catherine; Ordoñana, Juan R; Sánchez-Romera, Juan F; Colodro-Conde, Lucia; Gatz, Margaret; Butler, David A; Lichtenstein, Paul; Goldberg, Jack H; Harden, K Paige; Tucker-Drob, Elliot M; Duncan, Glen E; Buchwald, Dedra; Tarnoki, Adam D; Tarnoki, David L; Franz, Carol E; Kremen, William S; Lyons, Michael J; Maia, José A; Freitas, Duarte L; Turkheimer, Eric; Sørensen, Thorkild I A; Boomsma, Dorret I; Kaprio, Jaakko

2017-10-01

Whether monozygotic (MZ) and dizygotic (DZ) twins differ from each other in a variety of phenotypes is important for genetic twin modeling and for inferences made from twin studies in general. We analyzed whether there were differences in individual, maternal and paternal education between MZ and DZ twins in a large pooled dataset. Information was gathered on individual education for 218,362 adult twins from 27 twin cohorts (53% females; 39% MZ twins), and on maternal and paternal education for 147,315 and 143,056 twins respectively, from 28 twin cohorts (52% females; 38% MZ twins). Together, we had information on individual or parental education from 42 twin cohorts representing 19 countries. The original education classifications were transformed to education years and analyzed using linear regression models. Overall, MZ males had 0.26 (95% CI [0.21, 0.31]) years and MZ females 0.17 (95% CI [0.12, 0.21]) years longer education than DZ twins. The zygosity difference became smaller in more recent birth cohorts for both males and females. Parental education was somewhat longer for fathers of DZ twins in cohorts born in 1990-1999 (0.16 years, 95% CI [0.08, 0.25]) and 2000 or later (0.11 years, 95% CI [0.00, 0.22]), compared with fathers of MZ twins. The results show that the years of both individual and parental education are largely similar in MZ and DZ twins. We suggest that the socio-economic differences between MZ and DZ twins are so small that inferences based upon genetic modeling of twin data are not affected.

From equity to power: Critical Success Factors for Twinning between midwives, a Delphi study.

Science.gov (United States)

Cadée, Franka; Nieuwenhuijze, Marianne J; Lagro-Janssen, Antoine L M; de Vries, Raymond

2018-02-28

To gain consensus for Critical Success Factors associated with Twinning in Midwifery. International publications identify midwifery as important for improving maternity care worldwide. Midwifery is a team effort where midwives play a key role. Yet their power to take on this role is often lacking. Twinning has garnered potential to develop power in professionals, however, its success varies because implementation is not always optimal. Critical Success Factors have demonstrated positive results in the managerial context and can be helpful to build effective Twinning relationships. We approached 56 midwife Twinning experts from 19 countries to participate in three Delphi rounds between 2016 - 2017. In round 1, experts gave input through an open ended questionnaire and this was analysed to formulate Critical Success Factors statements that were scored on a 1-7 Likert scale aiming to gain consensus in rounds 2 and 3. These statements were operationalized for practical use such as a check list in planning, monitoring and evaluation in the field. Thirty-three experts from 14 countries took part in all three Delphi rounds, producing 58 initial statements. This resulted in 25 Critical Success Factors covering issues of management, communication, commitment and values, most focus on equity. The Critical Success Factors formulated represent the necessary ingredients for successful Twinning by providing a practical implementation framework and promote further research into the effect of Twinning. Findings show that making equity explicit in Twinning may contribute towards the power of midwives to take on their identified key role. © 2018 The Authors. Journal of Advanced Nursing Published by John Wiley & Sons Ltd.

A tale of twin Higgs: natural twin two Higgs doublet models

International Nuclear Information System (INIS)

Yu, Jiang-Hao

2016-01-01

In original twin Higgs model, vacuum misalignment between electroweak and new physics scales is realized by adding explicit ℤ 2 breaking term. Introducing additional twin Higgs could accommodate spontaneous ℤ 2 breaking, which explains origin of this misalignment. We introduce a class of twin two Higgs doublet models with most general scalar potential, and discuss general conditions which trigger electroweak and ℤ 2 symmetry breaking. Various scenarios on realising the vacuum misalignment are systematically discussed in a natural composite two Higgs double model framework: explicit ℤ 2 breaking, radiative ℤ 2 breaking, tadpole-induced ℤ 2 breaking, and quartic-induced ℤ 2 breaking. We investigate the Higgs mass spectra and Higgs phenomenology in these scenarios.

Using Twins to Better Understand Sibling Relationships.

Science.gov (United States)

Mark, Katharine M; Pike, Alison; Latham, Rachel M; Oliver, Bonamy R

2017-03-01

We compared the nature of the sibling relationship in dyads of varying genetic relatedness, employing a behavioural genetic design to estimate the contribution that genes and the environment have on this familial bond. Two samples were used-the Sisters and Brothers Study consisted of 173 families with two target non-twin children (mean ages = 7.42 and 5.22 years respectively); and the Twins, Family and Behaviour study included 234 families with two target twin children (mean age = 4.70 years). Mothers and fathers reported on their children's relationship with each other, via a postal questionnaire (the Sisters and Brothers Study) or a telephone interview (the Twins, Family and Behaviour study). Contrary to expectations, no mean level differences emerged when monozygotic twin pairs, dizygotic twin pairs, and non-twin pairs were compared on their sibling relationship quality. Behavioural genetic analyses also revealed that the sibling bond was modestly to moderately influenced by the genetic propensities of the children within the dyad, and moderately to substantially influenced by the shared environment common to both siblings. In addition, for sibling negativity, we found evidence of twin-specific environmental influence-dizygotic twins showed more reciprocity than did non-twins. Our findings have repercussions for the broader application of results from future twin-based investigations.

Aortic distensibility as a surrogate for intertwin pulse pressure differences in monochorionic pregnancies with and without twin-twin transfusion syndrome.

Science.gov (United States)

Wohlmuth, C; Osei, F A; Moise, K J; Johnson, A; Papanna, R; Bebbington, M; Gardiner, H M

2016-08-01

Twin-twin transfusion syndrome (TTTS) complicates 10-15% of monochorionic diamniotic (MCDA) twin pregnancies. The donor response to hypovolemia allows the transfer of vasoactive mediators to the recipient, causing increased recipient afterload and hypertension. Our objective was to apply a novel speckle-tracking technique to measure the aortic fractional area change (AFAC) during the cardiac cycle in MCDA twins with and without TTTS, and identify intertwin differences in AFAC and parameters of cardiac function. High-frame rate four-chamber views of the fetal heart, including the mid-thoracic aorta, were collected prospectively in MCDA twin pairs referred to our center between June 2014 and April 2015. Using speckle-tracking software, the endovascular border of the aorta was traced manually during systole, with guidance on cardiac cycle timing by anatomical M-mode. AFAC, defined as the difference between maximum and minimum area divided by minimum area, expressed as a percentage, was calculated offline and averaged over three cardiac cycles. Tissue Doppler and displacement were used to measure long-axis cardiac function. Intra- and interclass correlation coefficients were used to test observer variability. Fifty-one MCDA twin pregnancies were included, comprising uncomplicated MCDA (n = 14), TTTS Stages 1/2 (n = 21) and TTTS Stages 3/4 (n = 16). Median gestational age was 20.4 (range, 16.2-27.5) weeks. Mean ± SD heart rate was 142.6 ± 7.2 bpm with no significant intertwin pair differences. AFAC was significantly higher in recipients than in donors of TTTS pairs (Stages 1/2: 72.3 ± 29.9% vs 43.7 ± 19.3%, P pregnancies with TTTS. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

POU4F3 mutation screening in Japanese hearing loss patients: Massively parallel DNA sequencing-based analysis identified novel variants associated with autosomal dominant hearing loss.

Directory of Open Access Journals (Sweden)

Tomohiro Kitano

Full Text Available A variant in a transcription factor gene, POU4F3, is responsible for autosomal dominant nonsyndromic hereditary hearing loss, DFNA15. To date, 14 variants, including a whole deletion of POU4F3, have been reported to cause HL in various ethnic groups. In the present study, genetic screening for POU4F3 variants was carried out for a large series of Japanese hearing loss (HL patients to clarify the prevalence and clinical characteristics of DFNA15 in the Japanese population. Massively parallel DNA sequencing of 68 target candidate genes was utilized in 2,549 unrelated Japanese HL patients (probands to identify genomic variations responsible for HL. The detailed clinical features in patients with POU4F3 variants were collected from medical charts and analyzed. Novel 12 POU4F3 likely pathogenic variants (six missense variants, three frameshift variants, and three nonsense variants were successfully identified in 15 probands (2.5% among 602 families exhibiting autosomal dominant HL, whereas no variants were detected in the other 1,947 probands with autosomal recessive or inheritance pattern unknown HL. To obtain the audiovestibular configuration of the patients harboring POU4F3 variants, we collected audiograms and vestibular symptoms of the probands and their affected family members. Audiovestibular phenotypes in a total of 24 individuals from the 15 families possessing variants were characterized by progressive HL, with a large variation in the onset age and severity with or without vestibular symptoms observed. Pure-tone audiograms indicated the most prevalent configuration as mid-frequency HL type followed by high-frequency HL type, with asymmetry observed in approximately 20% of affected individuals. Analysis of the relationship between age and pure-tone average suggested that individuals with truncating variants showed earlier onset and slower progression of HL than did those with non-truncating variants. The present study showed that variants

Incidence of spontaneous twin anemia-polycythemia sequence in monochorionic-diamniotic twin pregnancies: Single-center prospective study.

Science.gov (United States)

Yokouchi, Tae; Murakoshi, Takeshi; Mishima, Takashi; Yano, Hiroko; Ohashi, Madoka; Suzuki, Takashi; Shinno, Takashi; Matsushita, Mitsuru; Nakayama, Satoru; Torii, Yuichi

2015-06-01

The purpose of this study was to prospectively estimate the incidence of spontaneous twin anemia-polycythemia sequence (TAPS) in monochorionic-diamniotic twin pregnancies. We prospectively examined umbilical cord hemoglobin (Hb) and reticulocyte count of consecutive monochorionic-diamniotic twin pregnancies delivered at Seirei Hamamatsu General Hospital from December 2006 to September 2013. We excluded cases of twin-twin transfusion syndrome, intrauterine fetal demise, and missing data (Hb and reticulocyte count missing from the medical record). TAPS was diagnosed using the postnatal criteria of intertwin Hb difference >8.0 g/dL and reticulocyte count ratio >1.7. Acute feto-fetal hemorrhage was defined as Hb difference >7 g/dL and reticulocyte count ratio <1.7. A total of 185 monochorionic-diamniotic twin pregnancies were included in this study. Three fulfilled the diagnostic criteria for postnatal TAPS, and one fulfilled the diagnostic criteria for acute feto-fetal hemorrhage. The incidence of spontaneous TAPS in monochorionic-diamniotic twin pregnancies was 1.6% (3/185) at Seirei Hamamatsu General Hospital. © 2014 The Authors. Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology.

Risk of sex-specific cancers in opposite-sex and same-sex twins in Denmark and Sweden

DEFF Research Database (Denmark)

Ahrenfeldt, Linda Juel; Skytthe, Axel; Möller, Sören

2015-01-01

-scale prospective twin study compared opposite-sex (OS) and same-sex (SS) twins to test the impact of intrauterine exposures on cancer risk. Based on the Danish and Swedish twin and cancer registries, we calculated incidence rate ratios for OS and SS twins while standardized incidence ratios (SIRs) with 95......% confidence intervals (CIs) were calculated for OS/SS twins compared with the general population. RESULTS: A total of 18,001 cancers were identified during 1943-2009. No significant differences were observed between OS and SS twins, neither for the sex-specific cancers nor for cancer at all sites. All...... to prenatal testosterone - does not increase the risk of sex-specific cancers in OS females. Furthermore, the study supports that twinning per se is not a risk factor of cancer. IMPACT: Findings are reassuring as they fail to provide evidence for the hypothesis that endocrine or other difference...

SUSY meets her twin

Energy Technology Data Exchange (ETDEWEB)

Katz, Andrey [Theory Division, CERN,CH-1211 Geneva 23 (Switzerland); Département de Physique Théorique and Center for Astroparticle Physics (CAP),Université de Genève,24 quai Ansermet, CH-1211 Genève 4 (Switzerland); Mariotti, Alberto [Theoretische Natuurkunde and IIHE/ELEM, Vrije Universiteit Brussel,and International Solvay Institutes,Pleinlaan 2, B-1050 Brussels (Belgium); Pokorski, Stefan [Institute of Theoretical Physics, Faculty of Physics, University of Warsaw,ul. Pasteura 5, PL-02-093 Warsaw (Poland); Redigolo, Diego [Raymond and Beverly Sackler School of Physics and Astronomy, Tel-Aviv University,Tel-Aviv 69978 (Israel); Department of Particle Physics and Astrophysics, Weizmann Institute of Science,Rehovot 7610001 (Israel); Ziegler, Robert [Institute for Theoretical Particle Physics (TTP), Karlsruhe Institute of Technology,Engesserstraße 7, D-76128 Karlsruhe (Germany)

2017-01-31

We investigate the general structure of mirror symmetry breaking in the Twin Higgs scenario. We show, using the IR effective theory, that a significant gain in fine tuning can be achieved if the symmetry is broken hardly. We emphasize that weakly coupled UV completions can naturally accommodate this scenario. We analyze SUSY UV completions and present a simple Twin SUSY model with a tuning of around 10% and colored superpartners as heavy as 2 TeV. The collider signatures of general Twin SUSY models are discussed with a focus on the extended Higgs sectors.

Pulmonary function in advanced uncomplicated singleton and twin pregnancy

Directory of Open Access Journals (Sweden)

Anwar Hasan Siddiqui

2014-06-01

Full Text Available Objective: Pregnancy brings about significant changes in respiratory function, as evidenced by alterations in lung volumes and capacities, which are attributable to the mechanical impediment caused by the growing foetus. This study was undertaken in order to identify changes in respiratory function during normal pregnancy and to determine whether such changes are more pronounced in twin pregnancy than in singleton pregnancy. Methods: Respiratory function was assessed in 50 women with twin pregnancies and in 50 women with singleton pregnancies (during the third trimester in both groups, as well as in 50 non-pregnant women. We measured the following pulmonary function test parameters: FVC; FEV1; PEF rate; FEV1/FVC ratio; FEF25-75%; and maximal voluntary ventilation. Results: All respiratory parameters except the FEV1/FVC ratio were found to be lower in the pregnant women than in the non-pregnant women. We found no significant differences between women with twin pregnancies and those with singleton pregnancies, in terms of respiratory function. Conclusions: Despite its higher physiological demands, twin pregnancy does not appear to impair respiratory function to any greater degree than does singleton pregnancy.

Monochorionic twin pregnancies: a systematic approach to ...

African Journals Online (AJOL)

Complications unique to these pregnancies include Twin-To-Twin Transfusion Syndrome (TTTS), Twin Polycythaemia Anaemia Sequence (TAPS), Selective Intrauterine Growth Restriction (sIUGR) and death of the co-twin. Adhering to a systematic and objective approach of management, can lead to early recognition and ...

Childhood and adult cancer in twins: evidence from the Utah genealogy.

Science.gov (United States)

Neale, Rachel E; Mineau, Geraldine; Whiteman, David C; Brownbill, Pat A; Murphy, Michael F G

2005-05-01

Evidence suggests that the in utero environment may contribute to subsequent development of cancers in childhood and adulthood. Raised levels of estrogen during pregnancy may be the primary in utero etiologic factor. Mothers of twins have higher estrogen levels during pregnancy than mothers of singletons, therefore, assessment of cancer risk in twins may be informative. We conducted a retrospective cohort study of cancer among twin and singleton newborns selected from the Utah Population Database, matched on birth year and sex. Cancer diagnoses were determined by linkage with the Utah state cancer register. Relative rates of all cancers in childhood and in adulthood in twins compared with singletons, and for specific cancers including testicular, breast and melanoma, were calculated using Poisson regression. Twin (35,271) and singleton (74,199) births were identified, among whom there were 336 and 691 cancer diagnoses, respectively. The relative risk (RR) of childhood cancer in twins compared with singletons was 0.82 [95% confidence interval (CI) 0.55-1.24] and of adult cancer was 1.06 (0.92-1.22). We found nonsignificant increases in risk among adult twins for cancers of the breast, prostate, testis, lymphatic system, thyroid, and large bowel. The largest departures from unity were for testicular cancer (RR 1.47; 95% CI, 0.73-2.95) and melanoma (RR 0.67; 95% CI, 0.42-1.06). These results are consistent with the body of evidence suggesting that twins have a reduced risk of cancer in childhood. Although there is no overall differential in adult cancer risk, these data support the hypothesis that the in utero environment may play an important role in specific cancers.

Longitudinal Investigation into Genetics in the Conservation of Metabolic Phenotypes in Danish and Chinese Twins

DEFF Research Database (Denmark)

Li, Shuxia; Kyvik, Kirsten Ohm; Duan, Haiping

2016-01-01

twin study on long-term stability of metabolic phenotypes in Danish and Chinese twins identified a common pattern of high genetic control over phenotype conservation, and at the same time revealed population-specific patterns of genetic and common environmental regulation on the variance as well...

Differences in the Expression of TLR-2, NOD2, and NF-κB in Placenta Between Twins.

Science.gov (United States)

Szylberg, Łukasz; Bodnar, Magdalena; Lebioda, Anna; Krepska, Patrycja; Kowalewski, Adam; Bręborowicz, Grzegorz; Marszałek, Andrzej

2018-05-23

Dizygotic twins share the same type of genetic relationship as non-twin siblings. Whereas monozygotic (MZ) twins are considered to have identical genetic material, they still differ. There is a number of reasons for early MZ twin discordance, including differences in the in utero environment, stochasticity, genetic mosaicism, and epigenetic factors. During gestation, the efficient innate immune system is of utmost importance. Our study was based on immunohistochemical evaluation of the differences in innate immune protein expression (TLR-2, NOD2, and NF-κB) in the 95 placentas between twins. Our study revealed statistical significant differences between diamniotic-dichorionic and monoamniotic-dichorionic twins. Monoamniotic-monochorionic twins exhibited no significant differences in protein expressions. To identify epigenetic factors causing the differences between twins, we made a series of comparisons with clinical data. The study revealed more cases with infections, miscarriages, in vitro fertilization, and premature rupture of membranes within the group with higher differences level of NF-κB, NOD2 and TLR-2 between twins. In case of twin-to-twin transfusion syndrome, there were no significant differences in innate immune protein expressions between twins. These results show that dissimilar genetic material and separate in utero environment promote discordance in innate immune protein expressions between twins. Moreover, additional blood flow between twins may be favorable in life-threatening conditions ensuring similar microenvironment.

Combined analyses of 20 common obesity susceptibility variants

DEFF Research Database (Denmark)

Sandholt, Camilla Helene; Sparsø, Thomas; Grarup, Niels

2010-01-01

Genome-wide association studies and linkage studies have identified 20 validated genetic variants associated with obesity and/or related phenotypes. The variants are common, and they individually exhibit small-to-modest effect sizes.......Genome-wide association studies and linkage studies have identified 20 validated genetic variants associated with obesity and/or related phenotypes. The variants are common, and they individually exhibit small-to-modest effect sizes....

A tale of twin Higgs: natural twin two Higgs doublet models

Energy Technology Data Exchange (ETDEWEB)

Yu, Jiang-Hao [Amherst Center for Fundamental Interactions, Department of Physics,University of Massachusetts Amherst,710 North Pleasant St., Amherst, MA 01002 (United States)

2016-12-28

In original twin Higgs model, vacuum misalignment between electroweak and new physics scales is realized by adding explicit ℤ{sub 2} breaking term. Introducing additional twin Higgs could accommodate spontaneous ℤ{sub 2} breaking, which explains origin of this misalignment. We introduce a class of twin two Higgs doublet models with most general scalar potential, and discuss general conditions which trigger electroweak and ℤ{sub 2} symmetry breaking. Various scenarios on realising the vacuum misalignment are systematically discussed in a natural composite two Higgs double model framework: explicit ℤ{sub 2} breaking, radiative ℤ{sub 2} breaking, tadpole-induced ℤ{sub 2} breaking, and quartic-induced ℤ{sub 2} breaking. We investigate the Higgs mass spectra and Higgs phenomenology in these scenarios.

A study of the occurrence of monochorionic and monozygotic twinning in the pig

DEFF Research Database (Denmark)

Bjerre, Ditte; Thorup, F.; Jørgensen, Claus Bøttcher

2009-01-01

the investigation of porcine monochorionic embryos from 76 sows at days 26-29 post-insemination (p.i.), as well as an examination of 10 whole litters at days 21-22 p.i. In the former group, 29% of the sows carried monochorionic embryos. Based on DNA profiling using microsatellite markers, one monozygotic twin pair...... was found among these embryos. In the latter group, three monozygotic twin pairs were identified. Thus, it can be concluded that although the occurrence of monozygotic twins in pigs is a sporadic event, the fusion of extra-embryonic membranes is relatively common....

Risk factors for cesarean delivery and adverse neonatal outcome in twin pregnancies attempting vaginal delivery.

Science.gov (United States)

Schachter-Safrai, Natali; Karavani, Gilad; Haj-Yahya, Rani; Ofek Shlomai, Noa; Porat, Shay

2018-02-24

Twin vaginal delivery presents a unique clinical challenge for obstetricians. The Twin Birth Study demonstrated the safety of planned vaginal delivery regarding neonatal outcomes. However, that study lacked a description of the risk factors associated with and the outcome of unplanned cesarean section. The aim of this study is to identify potential risk factors for cesarean section and delivery related neonatal morbidity and mortality in women with twin pregnancy attempting vaginal delivery. A retrospective cohort study including 1070 women with twin pregnancy that underwent a trial of labor between 2003 and 2015. The study population was divided according to the mode of delivery: vaginal delivery, combined vaginal-cesarean and intrapartum cesarean delivery of both twins. Several risk factors and neonatal outcomes were examined by both univariate analysis and multinomial logistic regression analysis. The rate of vaginal delivery of both twins was 88.3%, whereas the rates of combined vaginal cesarean and unplanned cesarean delivery were 4.6% and 7.1%, respectively. Nulliparity and nonvertex presentation of twin B were found to be independently associated with cesarean delivery for both twins. Additionally, nonvertex presentation of twin B was independently associated with combined vaginal-cesarean delivery. The proportion of neonates with Apgar score cesarean group compared with those delivered by the vaginal route alone. Nulliparity and nonvertex presentation of twin B were found to be associated with intrapartum cesarean delivery in twin pregnancies. © 2018 Nordic Federation of Societies of Obstetrics and Gynecology.

Shotgun metagenomics of 250 adult twins reveals genetic and environmental impacts on the gut microbiome

DEFF Research Database (Denmark)

Xie, Hailiang; Guo, Ruijin; Zhong, Huanzi

2016-01-01

The gut microbiota has been typically viewed as an environmental factor for human health. Twins are well suited for investigating the concordance of their gut microbiomes and decomposing genetic and environmental influences. However, existing twin studies utilizing metagenomic shotgun sequencing...... have included only a few samples. Here, we sequenced fecal samples from 250 adult twins in the TwinsUK registry and constructed a comprehensive gut microbial reference gene catalog. We demonstrate heritability of many microbial taxa and functional modules in the gut microbiome, including those...... associated with diseases. Moreover, we identified 8 million SNPs in the gut microbiome and observe a high similarity in microbiome SNPs between twins that slowly decreases after decades of living apart. The results shed new light on the genetic and environmental influences on the composition and function...

Establishing a Twin Registry in Guinea-Bissau

DEFF Research Database (Denmark)

Bjerregaard-Andersen, Morten; Gomes, Margarida A; Joaquím, Luis C

2013-01-01

represent a powerful tool. Though twin studies have been carried out by the Bandim Health Project for more than 30 years, the renewed registry described here was officially established in 2009 and includes both a cohort of newborn twins and a cohort of young and adult twins. Currently more than 1,500 twins...

Anorexia and bulimia nervosa in same-sex and opposite-sex twins: lack of association with twin type in a nationwide study of Finnish twins.

Science.gov (United States)

Raevuori, Anu; Kaprio, Jaakko; Hoek, Hans W; Sihvola, Elina; Rissanen, Aila; Keski-Rahkonen, Anna

2008-12-01

The authors tested the hypothesis that either prenatal feminization or masculinization hormone influences in utero or later socialization affects the risk for anorexia and bulimia nervosa and disordered eating in members of opposite-sex twin pairs. Finnish twins (N=2,426 women, N=1,962 men with known zygosity) from birth cohorts born 1974-1979 were assessed at age 22 to 28 years with a questionnaire for eating disorder symptoms. Based on the questionnaire screen, women (N=292), men (N=53), and their cotwins were interviewed to assess diagnoses of anorexia nervosa and bulimia nervosa (per DSM-IV and broad criteria). In women from opposite-sex twin pairs, the prevalence of DSM-IV or broad anorexia nervosa was not significantly different than that of women from monozygotic pairs or same-sex dizygotic pairs. Of the five male anorexia nervosa probands, only one was from an opposite-sex twin pair. Bulimia nervosa in men was too rare to be assessed by zygosity; the prevalence of DSM-IV or broad bulimia nervosa did not differ in women from opposite- versus same-sex twin pairs. In both sexes, the overall profile of indicators on eating disorders was rather similar between individuals from opposite- and same-sex pairs. The authors found little evidence that the risk for anorexia nervosa, bulimia nervosa, or disordered eating was associated with zygosity or sex composition of twin pairs, thus making it unlikely that in utero femininization or masculinization or socialization effects of growing up with an opposite-sex twin have a major influence on the later development of eating disorders.

Heteropagus twinning on back -- a case report.

Science.gov (United States)

Debnath, Bidyut; Biswas, Sumitra Kumar

2011-07-01

Heteropagus twins, also called parasitic twins, are malformation of the foetus where the development of one twin is incomplete. They are attached most commonly to the lower chest and upper abdomen. We report a case of heteropagus twin, where the parasite possessed well-formed limb as well as blind ending intestine. It was attached to the back of the host by a broad pedicle. We take this opportunity to classify areas of confusion prevailing regarding twinning, foetus in foetu, teratoma and caudal duplication.

Risk and protective factors for Parkinson's disease: a study in Swedish twins.

Science.gov (United States)

Wirdefeldt, Karin; Gatz, Margaret; Pawitan, Yudi; Pedersen, Nancy L

2005-01-01

Many studies have shown a protective effect of cigarette smoking on Parkinson's disease. However, criticism has been raised concerning confounding by genetic factors. We investigated the associations between Parkinson's disease and smoking, alcohol, coffee, area of living, and education in a co-twin control study. Because twins are matched for genetic and familial environmental factors, this design controls for confounding by these factors. We also examined control subjects unrelated to cases. Exposure information was taken from questionnaires answered in the 1960s and 1970s. Parkinson's disease cases were identified through the Swedish Inpatient Discharge Register (IDR) and the Cause of Death Register. In the unrelated control subject comparison, 476 Parkinson's disease cases and 2,380 control subjects were included. In the co-twin control comparison, 415 same-sex twin pairs were included. There was an inverse association between smoking and Parkinson's disease using unrelated control subjects and co-twin control cases. There was no association between Parkinson's disease and alcohol, coffee, or area of living. High educational level was associated with Parkinson's disease in the unrelated control subject comparison but not in the co-twin control comparison. We confirm the protective effect of smoking on Parkinson's disease and establish that the association is only partially explained by genetic and familial environmental factors.

Time trends in the natural dizygotic twinning rate.

Science.gov (United States)

Derom, Catherine; Gielen, Marij; Peeters, Hilde; Frijns, Jean-Pierre; Zeegers, Maurice P A

2011-08-01

The natural dizygotic (DZ) twinning rate has been proposed as a reliable and useful measure of human fecundity, if adjusted for maternal age at twin birth. The aim of this study was to analyze age-adjusted trends in natural DZ twinning rates over the past 40 years using data from the 'East Flanders Prospective Twin Survey (EFPTS)'. This study involved 4835 naturally conceived twin pregnancies between 1969 and 2009 from the population-based Belgian 'EFPTS'. Age-adjusted trends in the incidence of natural DZ twin pregnancies were calculated using a generalized linear model with Poisson distribution. Both the natural DZ twinning rates and maternal age at twin birth increased in a linear fashion from 1969 to 2009. When age-adjusted, we found that the trend in the natural DZ twinning rate was stable during the whole time period. According to our population-based data and after age-adjustment, a stable natural DZ twinning rate could be observed over the last four decades. Under the assumption that the spontaneous DZ twinning rate is a sensor of fecundity, this indicates a stable 'high' fecundity for this population.

A quadratically regularized functional canonical correlation analysis for identifying the global structure of pleiotropy with NGS data.

Science.gov (United States)

Lin, Nan; Zhu, Yun; Fan, Ruzong; Xiong, Momiao

2017-10-01

Investigating the pleiotropic effects of genetic variants can increase statistical power, provide important information to achieve deep understanding of the complex genetic structures of disease, and offer powerful tools for designing effective treatments with fewer side effects. However, the current multiple phenotype association analysis paradigm lacks breadth (number of phenotypes and genetic variants jointly analyzed at the same time) and depth (hierarchical structure of phenotype and genotypes). A key issue for high dimensional pleiotropic analysis is to effectively extract informative internal representation and features from high dimensional genotype and phenotype data. To explore correlation information of genetic variants, effectively reduce data dimensions, and overcome critical barriers in advancing the development of novel statistical methods and computational algorithms for genetic pleiotropic analysis, we proposed a new statistic method referred to as a quadratically regularized functional CCA (QRFCCA) for association analysis which combines three approaches: (1) quadratically regularized matrix factorization, (2) functional data analysis and (3) canonical correlation analysis (CCA). Large-scale simulations show that the QRFCCA has a much higher power than that of the ten competing statistics while retaining the appropriate type 1 errors. To further evaluate performance, the QRFCCA and ten other statistics are applied to the whole genome sequencing dataset from the TwinsUK study. We identify a total of 79 genes with rare variants and 67 genes with common variants significantly associated with the 46 traits using QRFCCA. The results show that the QRFCCA substantially outperforms the ten other statistics.

Genetic variants in the choline acetyltransferase (ChAT) gene are modestly associated with normal cognitive function in the elderly

DEFF Research Database (Denmark)

Mengel-From, J; Christensen, K; Thinggaard, M

2011-01-01

Genetic variants in the choline acetyltransferase (ChAT) gene have been suggested as risk factors for neurodegenerative Alzheimer's disease (AD). Here we tested the importance of genetic variants in the ChAT gene in normal cognitive function of elderly in a study sample of Danish twins...... and singletons (N = 2070). The ChAT rs3810950 A allele, which has been associated with increased risk for AD, was found to be associated with a decrease cognitive status evaluated by a five-component cognitive composite score [P = 0.03, regression coefficient -0.30, 95% confidence interval (CI) -0.57 to -0...

Semantic prioritization of novel causative genomic variants

KAUST Repository

Boudellioua, Imene

2017-04-17

Discriminating the causative disease variant(s) for individuals with inherited or de novo mutations presents one of the main challenges faced by the clinical genetics community today. Computational approaches for variant prioritization include machine learning methods utilizing a large number of features, including molecular information, interaction networks, or phenotypes. Here, we demonstrate the PhenomeNET Variant Predictor (PVP) system that exploits semantic technologies and automated reasoning over genotype-phenotype relations to filter and prioritize variants in whole exome and whole genome sequencing datasets. We demonstrate the performance of PVP in identifying causative variants on a large number of synthetic whole exome and whole genome sequences, covering a wide range of diseases and syndromes. In a retrospective study, we further illustrate the application of PVP for the interpretation of whole exome sequencing data in patients suffering from congenital hypothyroidism. We find that PVP accurately identifies causative variants in whole exome and whole genome sequencing datasets and provides a powerful resource for the discovery of causal variants.

Semantic prioritization of novel causative genomic variants

KAUST Repository

Boudellioua, Imene; Mohamad Razali, Rozaimi; Kulmanov, Maxat; Hashish, Yasmeen; Bajic, Vladimir B.; Goncalves-Serra, Eva; Schoenmakers, Nadia; Gkoutos, Georgios V.; Schofield, Paul N.; Hoehndorf, Robert

2017-01-01

Discriminating the causative disease variant(s) for individuals with inherited or de novo mutations presents one of the main challenges faced by the clinical genetics community today. Computational approaches for variant prioritization include machine learning methods utilizing a large number of features, including molecular information, interaction networks, or phenotypes. Here, we demonstrate the PhenomeNET Variant Predictor (PVP) system that exploits semantic technologies and automated reasoning over genotype-phenotype relations to filter and prioritize variants in whole exome and whole genome sequencing datasets. We demonstrate the performance of PVP in identifying causative variants on a large number of synthetic whole exome and whole genome sequences, covering a wide range of diseases and syndromes. In a retrospective study, we further illustrate the application of PVP for the interpretation of whole exome sequencing data in patients suffering from congenital hypothyroidism. We find that PVP accurately identifies causative variants in whole exome and whole genome sequencing datasets and provides a powerful resource for the discovery of causal variants.

Relationship between refractive error and ocular biometrics in twin children: the Guangzhou Twin Eye Study.

Science.gov (United States)

Wang, Decai; Liu, Bin; Huang, Shengsong; Huang, Wenyong; He, Mingguang

2014-09-01

A cross-sectional study was conducted to explore the relationship between refractive error and ocular biometrics in children from the Guangzhou twin eye study. Twin participants aged 7-15 years were selected from Guangzhou Twin Eye Study. Ocular examinations included visual acuity measurement, ocular motility evaluation, autorefraction under cycloplegia, and anterior segment, media, and fundus examination. Axial length (AL), anterior chamber depth (ACD), and corneal curvature radius were measured using partial coherence laser interferometry. A multivariate linear regression model was used for statistical analysis. Twin children from Guangzhou city showed a decreased spherical equivalent with age, whereas both AL and ACD were increased and corneal curvature radius remained unchanged. When adjusted by age and gender, the data from 77% of twins presenting with spherical equivalent changes indicated that these were caused by predictable variables (R2 = 0.77, P biometrics. Refractive status is largely determined by axial length as the major factor.

Twins with omphalocele in Denmark (1970-1989)

DEFF Research Database (Denmark)

Bugge, Merete

2010-01-01

Seven pairs of twins, two monozygotic (MZ), two dizygotic (DZ), and three like-sex pairs of unknown zygosity are described. The twin pairs were all discordant for omphalocele except for one pair of conjoined twins. The 8 infants with omphalocele represent 3.1% of the 253 infants with omphalocele......, ascertained in an almost complete nationwide data set of live- and stillborn infants with abdominal wall defects in two decades in Denmark (1970-1989). The occurrence of twins with omphalocele was not significantly different from the occurrence of twins in the Danish population in the same period. To our...... knowledge this is the first report of the occurrence of twins with omphalocele in a systematic nationwide epidemiological study....

Twin anemia polycythemia sequence

NARCIS (Netherlands)

Slaghekke, Femke

2014-01-01

In this thesis we describe that Twin Anemia Polycythemia Sequence (TAPS) is a form of chronic feto-fetal transfusion in monochorionic (identical) twins based on a small amount of blood transfusion through very small anastomoses. For the antenatal diagnosis of TAPS, Middle Cerebral Artery – Peak

The Danish Twin Registry

DEFF Research Database (Denmark)

Skytthe, Axel; Ohm Kyvik, Kirsten; Vilstrup Holm, Niels

2011-01-01

Introduction: The Danish Twin Registry is a unique source for studies of genetic, familial and environmental factors on life events, health conditions and diseases. Content: More than 85,000 twin pairs born 1870-2008 in Denmark. Validity and coverage: Four main ascertainment methods have been emp...

Nature versus nurture: identical twins and bariatric surgery.

Science.gov (United States)

Hagedorn, Judith C; Morton, John M

2007-06-01

Genetics and environment both play a role in weight maintenance. Twin studies may help clarify the influence of nature vs nurture in weight loss. We present the largest U.S. experience with monozygotic (MZ) twins undergoing bariatric surgery. We retrospectively reviewed the charts of four sets of MZ twins who underwent Roux-en-Y gastric bypass (RYGBP) surgery and laparoscopic adjustable gastric band (LAGB) placement at three different institutions. BMI and co-morbidities were examined pre- and postoperatively, and laboratory values were recorded. All four sets of twins are female, live together, and have similar professions. Twin cohort 1 had near identical weight loss patterns after open RYGBP surgery in 1996 (preop 146/142 kg; 2 years 82/82; and 10 years 108/107). Twin cohort 1 also both underwent cholecystectomies within the first year postoperatively. Twin cohort 2 underwent laparoscopic RYGBP surgery and also required cholecystectomies in the first postoperative year. Cohort 2 also experienced nearly identical weight loss at 1 year (36.7% vs 37.0% BMI loss). Twin cohort 3 underwent LAGB placement with two different surgeons with differing amounts of weight loss at 6 months (6.5% vs 15.7% BMI loss). Finally, twin cohort 4 underwent laparoscopic RYGBP with 2-year BMI loss of 39% vs 34%. In twin cohort 4, the twin who lost less weight lived apart from her twin and extended family, and her weight loss was less than the twin living with her family. Two sets of MZ twins had identical responses to bariatric surgery. The other two sets of identical twins had differential weight loss results, possibly due to differences in surgical approach and social support. While genetics do exert a strong influence on weight loss and maintenance, this case series demonstrates the potential effect of social support and postoperative management upon postoperative weight loss in the presence of identical genetics.

A study of diabetes mellitus within a large sample of Australian twins

DEFF Research Database (Denmark)

Condon, Julianne; Shaw, Joanne E; Luciano, Michelle

2008-01-01

with type 2 diabetes (T2D), 41 female pairs with gestational diabetes (GD), 5 pairs with impaired glucose tolerance (IGT) and one pair with MODY. Heritabilities of T1D, T2D and GD were all high, but our samples did not have the power to detect effects of shared environment unless they were very large......Twin studies of diabetes mellitus can help elucidate genetic and environmental factors in etiology and can provide valuable biological samples for testing functional hypotheses, for example using expression and methylation studies of discordant pairs. We searched the volunteer Australian Twin...... Registry (19,387 pairs) for twins with diabetes using disease checklists from nine different surveys conducted from 1980-2000. After follow-up questionnaires to the twins and their doctors to confirm diagnoses, we eventually identified 46 pairs where one or both had type 1 diabetes (T1D), 113 pairs...

Illustrations of the twin paradox

International Nuclear Information System (INIS)

Rebhan, E.

1985-01-01

In order to provide a more intuitive understanding of the twin paradox, several illustrations of this are presented. In one of these, each of the twins is equipped with a lamp whose monochromatic light can be observed by the other. In other illustrations the travelling twin uses an Einstein train instead of a space ship, all the cars of the train and all stations along the route of the train being equipped with clocks. (author)

Twins in Ancient Greece: a synopsis.

Science.gov (United States)

Malamitsi-Puchner, Ariadne

2016-01-01

This brief outline associates twins with several aspects of life in Ancient Greece. In Greek mythology twins caused ambivalent reactions and were believed to have ambivalent feelings for each other. Very often, they were viewed as the representatives of the dualistic nature of the universe. Heteropaternal superfecundation, which dominates in ancient myths, explains on one hand, the god-like qualities and, on the other hand, the mortal nature of many twins. An assumption is presented that legends referring to twins might reflect the territorial expansions of Ancient Greeks in Northern Mediterranean, around the Black Sea, in Asia Minor, as well as North East Africa. In conclusion, in Greek antiquity, twins have been used as transitional figures between myth and reality.

Identification of risk loci with shared effects on five major psychiatric disorders

DEFF Research Database (Denmark)

Steinhausen, Hans-Christoph E.; Strauss, John; Strohmaier, Jana

2013-01-01

Findings from family and twin studies suggest that genetic contributions to psychiatric disorders do not in all cases map to present diagnostic categories. We aimed to identify specific variants underlying genetic effects shared between the five disorders in the Psychiatric Genomics Consortium: a......: autism spectrum disorder, attention deficit-hyperactivity disorder, bipolar disorder, major depressive disorder, and schizophrenia.......Findings from family and twin studies suggest that genetic contributions to psychiatric disorders do not in all cases map to present diagnostic categories. We aimed to identify specific variants underlying genetic effects shared between the five disorders in the Psychiatric Genomics Consortium...

Risk factors for Staphylococcus aureus nasal colonization in Danish middle-aged and elderly twins

DEFF Research Database (Denmark)

Andersen, P S; Larsen, Lisbeth Aagaard; Fowler, V G

2013-01-01

on S. aureus carriage in Danish middle-aged and elderly twins, which indicated no significant heritability that could account for the observed S. aureus carriage. In the present study, we performed a questionnaire-based study of S. aureus colonization on the same cohort of 2,196 Danish middle......-aged and elderly twins to identify specific risk factors for S. aureus nasal colonization, including analyzing the paired twins (n = 478) that were discordant for S. aureus colonization. We found associations between risk factors and S. aureus nasal colonization among middle-aged and elderly twins, including age......, male gender, psoriasis, and atopic diseases. Also, present living on a farm is clearly associated with S. aureus colonization, while smoking had a borderline statistically significant protective effect....

Genome-wide local ancestry approach identifies genes and variants associated with chemotherapeutic susceptibility in African Americans.

Directory of Open Access Journals (Sweden)

Heather E Wheeler

Full Text Available Chemotherapeutic agents are used in the treatment of many cancers, yet variable resistance and toxicities among individuals limit successful outcomes. Several studies have indicated outcome differences associated with ancestry among patients with various cancer types. Using both traditional SNP-based and newly developed gene-based genome-wide approaches, we investigated the genetics of chemotherapeutic susceptibility in lymphoblastoid cell lines derived from 83 African Americans, a population for which there is a disparity in the number of genome-wide studies performed. To account for population structure in this admixed population, we incorporated local ancestry information into our association model. We tested over 2 million SNPs and identified 325, 176, 240, and 190 SNPs that were suggestively associated with cytarabine-, 5'-deoxyfluorouridine (5'-DFUR-, carboplatin-, and cisplatin-induced cytotoxicity, respectively (p≤10(-4. Importantly, some of these variants are found only in populations of African descent. We also show that cisplatin-susceptibility SNPs are enriched for carboplatin-susceptibility SNPs. Using a gene-based genome-wide association approach, we identified 26, 11, 20, and 41 suggestive candidate genes for association with cytarabine-, 5'-DFUR-, carboplatin-, and cisplatin-induced cytotoxicity, respectively (p≤10(-3. Fourteen of these genes showed evidence of association with their respective chemotherapeutic phenotypes in the Yoruba from Ibadan, Nigeria (p<0.05, including TP53I11, COPS5 and GAS8, which are known to be involved in tumorigenesis. Although our results require further study, we have identified variants and genes associated with chemotherapeutic susceptibility in African Americans by using an approach that incorporates local ancestry information.

Twin birth order, birthweight and birthweight discordance: any relationship

Directory of Open Access Journals (Sweden)

Onyiriuka A.N.

2010-12-01

Full Text Available Background: It is widely believed that in twin pairs, at birth, the first-born weigh more than the second-born but this concept has been challenged. Objective: To assess the truthfulness of this common concept that first-born twins are usually heavier than their second-born siblings at birth. Methods: In a series of 104 sets of live-born twins, the birth weights of first-born twins were compared with those of their second-born siblings, after controlling for gender. Their intra-pair birthweight differences were determined and twin pairs whose birthweight difference was 15% or more were designated as discordant. Results: Twin I was heavier than Twin II in 61.5% of cases while Twin II was heavier than Twin I in 28.9% of cases. Twins I and II had equal birthweights in 9.6% of cases. Comparing the mean birthweight of the first-born-male twin with that of second-born- male twin, it was 2515+427g (95% Confidence Interval, CI=2402-2628 versus 2432 +435g (95% CI=2321-2543 p>0.05. The mean birthweight of first-born-female twin was 2326+445g (95% CI=2214-2439 while that of the second-born-female twin was 2325+501g (95% CI=2197-2453 p>0.05. When the birthweight difference exceeded 750g, the probability that Twin I will be heavier than Twin II was 83.3% (5 of 6. Conclusion: Although the first-born twin was more often heavier than their second-born siblings, either could weigh more or less at birth. The larger the birthweight difference between growth-discordant twin pair, the greater the probability that the heavier twin would be delivered first

Variants in the Dopamine-4-Receptor Gene Promoter Are Not Associated with Sensation Seeking in Skiers

OpenAIRE

Thomson, Cynthia J.; Rajala, Amelia K.; Carlson, Scott R.; Rupert, Jim L.

2014-01-01

Sensation seeking is a personality trait that has been associated with disinhibited behaviours including substance use and gambling, but also with high-risk sport practices including skydiving, paragliding, and downhill skiing. Twin studies have shown that sensation seeking is moderately heritable, and candidate genes encoding components involved in dopaminergic transmission have been investigated as contributing to this type of behaviour. To determine whether variants in the regulatory regio...

CDKL5 variants

Science.gov (United States)

Kalscheuer, Vera M.; Hennig, Friederike; Leonard, Helen; Downs, Jenny; Clarke, Angus; Benke, Tim A.; Armstrong, Judith; Pineda, Mercedes; Bailey, Mark E.S.; Cobb, Stuart R.

2017-01-01

Objective: To provide new insights into the interpretation of genetic variants in a rare neurologic disorder, CDKL5 deficiency, in the contexts of population sequencing data and an updated characterization of the CDKL5 gene. Methods: We analyzed all known potentially pathogenic CDKL5 variants by combining data from large-scale population sequencing studies with CDKL5 variants from new and all available clinical cohorts and combined this with computational methods to predict pathogenicity. Results: The study has identified several variants that can be reclassified as benign or likely benign. With the addition of novel CDKL5 variants, we confirm that pathogenic missense variants cluster in the catalytic domain of CDKL5 and reclassify a purported missense variant as having a splicing consequence. We provide further evidence that missense variants in the final 3 exons are likely to be benign and not important to disease pathology. We also describe benign splicing and nonsense variants within these exons, suggesting that isoform hCDKL5_5 is likely to have little or no neurologic significance. We also use the available data to make a preliminary estimate of minimum incidence of CDKL5 deficiency. Conclusions: These findings have implications for genetic diagnosis, providing evidence for the reclassification of specific variants previously thought to result in CDKL5 deficiency. Together, these analyses support the view that the predominant brain isoform in humans (hCDKL5_1) is crucial for normal neurodevelopment and that the catalytic domain is the primary functional domain. PMID:29264392

Deformation Behavior of a Coarse-Grained Mg-8Al-1.5Ca-0.2Sr Magnesium Alloy at Elevated Temperatures

Science.gov (United States)

Lou, Yan; Liu, Xiao

2018-02-01

The compression tests were carried out on a coarse-grained Mg-8Al-1.5Ca-0.2Sr magnesium alloy samples at temperatures from 300 to 450 °C and strain rates from 0.001 to 10 s-1. The flow stress curves were analyzed using the double-differentiation method, and double minima were detected on the flow curves. The first set of minima is shown to identify the critical strain for twinning, while the second set indicates the critical strain for the initiation of dynamic recrystallization (DRX). Twin variant selection was numerically identified by comprehensive analysis of the Schmid factors for different deformation modes and the accommodation strains imposed on neighboring grains. It was found that twinning is initiated before DRX. Dynamic recrystallization volume increases with strain rate at a given deformation temperature. At high strain rate, various twin variants are activated to accommodate deformation, leading to the formation of twin intersections and high DRX volume. Fully dynamic recrystallized structure can be obtained at both high and low strain rates due to the high mobility of the grain and twin boundaries at the temperature of 400 °C.

Twinning behavior in the Ti-5at.% Al single crystals during cyclic loading along [0001

International Nuclear Information System (INIS)

Xiao Lin

2005-01-01

Cyclic deformation behavior of Ti-5at.% Al single crystals subjected to pull-push cyclic load along [0001] crystallographic orientation was studied. A higher cyclic stress response was displayed in the Ti-5Al single crystal oriented for [0001] than that oriented for single prism slip. Optical microscopy and transmission electron microscopy examinations show that twinning is a dominant plastic deformation mode in the single crystals during cycling. Trace analysis of prepolished surfaces was used to identify the twin systems primarily responsible for deformation. The major twin type observed was {101-bar 2}, {112-bar 2}, {101-bar 1} and {112-bar 1}. slip was observed in the neighboring region of twins in the fatigued specimens. The activation of multiple twinning systems contributed to the higher cyclic saturation stress in Ti-5Al single crystals oriented for [0001

The Role of Grain Orientation and Grain Boundary Characteristics in the Mechanical Twinning Formation in a High Manganese Twinning-Induced Plasticity Steel

Science.gov (United States)

Shterner, Vadim; Timokhina, Ilana B.; Rollett, Anthony D.; Beladi, Hossein

2018-04-01

In the current study, the dependence of mechanical twinning on grain orientation and grain boundary characteristics was investigated using quasi in-situ tensile testing. The grains of three main orientations (i.e., , , and parallel to the tensile axis (TA)) and certain characteristics of grain boundaries (i.e., the misorientation angle and the inclination angle between the grain boundary plane normal and the TA) were examined. Among the different orientations, and were the most and the least favored orientations for the formation of mechanical twins, respectively. The orientation was intermediate for twinning. The annealing twin boundaries appeared to be the most favorable grain boundaries for the nucleation of mechanical twinning. No dependence was found for the inclination angle of annealing twin boundaries, but the orientation of grains on either side of the annealing twin boundary exhibited a pronounced effect on the propensity for mechanical twinning. Annealing twin boundaries adjacent to high Taylor factor grains exhibited a pronounced tendency for twinning regardless of their inclination angle. In general, grain orientation has a significant influence on twinning on a specific grain boundary.

Evaluating genome-wide association study-identified breast cancer risk variants in African-American women.

Directory of Open Access Journals (Sweden)

Jirong Long

Full Text Available Genome-wide association studies (GWAS, conducted mostly in European or Asian descendants, have identified approximately 67 genetic susceptibility loci for breast cancer. Given the large differences in genetic architecture between the African-ancestry genome and genomes of Asians and Europeans, it is important to investigate these loci in African-ancestry populations. We evaluated index SNPs in all 67 breast cancer susceptibility loci identified to date in our study including up to 3,300 African-American women (1,231 cases and 2,069 controls, recruited in the Southern Community Cohort Study (SCCS and the Nashville Breast Health Study (NBHS. Seven SNPs were statistically significant (P ≤ 0.05 with the risk of overall breast cancer in the same direction as previously reported: rs10069690 (5p15/TERT, rs999737 (14q24/RAD51L1, rs13387042 (2q35/TNP1, rs1219648 (10q26/FGFR2, rs8170 (19p13/BABAM1, rs17817449 (16q12/FTO, and rs13329835 (16q23/DYL2. A marginally significant association (P<0.10 was found for three additional SNPs: rs1045485 (2q33/CASP8, rs4849887 (2q14/INHBB, and rs4808801 (19p13/ELL. Three additional SNPs, including rs1011970 (9p21/CDKN2A/2B, rs941764 (14q32/CCDC88C, and rs17529111 (6q14/FAM46A, showed a significant association in analyses conducted by breast cancer subtype. The risk of breast cancer was elevated with an increasing number of risk variants, as measured by quintile of the genetic risk score, from 1.00 (reference, to 1.75 (1.30-2.37, 1.56 (1.15-2.11, 2.02 (1.50-2.74 and 2.63 (1.96-3.52, respectively, (P = 7.8 × 10(-10. Results from this study highlight the need for large genetic studies in AAs to identify risk variants impacting this population.

Testicular cancer in twins: a meta-analysis.

Science.gov (United States)

Neale, R E; Carrière, P; Murphy, M F G; Baade, P D

2008-01-15

In a meta-analysis of testicular cancer in twins, twins had a 30% increased risk (estimate 1.31, 95% CI 1.1-1.6), providing indirect support for the hypothesis that in utero hormone variations influence risk of testicular cancer. The summary-estimate for dizygotic twins was 1.3 (1.0-1.7) and for monozygotic or same sex twins 1.4 (1.2-1.8).

The Mid-Atlantic Twin Registry, revisited.

Science.gov (United States)

Lilley, Emily C H; Silberg, Judy L

2013-02-01

The Mid-Atlantic Twin Registry (MATR) is a population-based registry of more than 56,000 twins primarily born or living in Virginia, North Carolina, and South Carolina. The MATR employs several methods of ascertaining twins, and devotes considerable resources to tracking and maintaining communication with MATR participants. Researchers may utilize the MATR for administration of research services including study recruitment, collection of DNA, archival data set creation, as well as data collection through mailed, phone, or online surveys. In addition, the MATR houses the MATR Repository, with over 1,200 blood samples available for researchers interested in DNA genotyping. For over 35 years MATR twins have participated in research studies with investigators from diverse scientific disciplines and various institutions. These studies, which have resulted in numerous publications, have covered a range of topics, including the human microbiome, developmental psychopathology, depression, anxiety, substance use, epigenetics of aging, children of twins, pre-term birth, social attitudes, seizures, eating disorders, as well as sleep homeostasis. Researchers interested in utilizing twins are encouraged to contact the MATR to discuss potential research opportunities.

Prosocial and self-interested intra-twin pair behavior in monozygotic and dizygotic twins in the early to middle childhood transition.

Science.gov (United States)

Yirmiya, Karen; Segal, Nancy L; Bloch, Guy; Knafo-Noam, Ariel

2018-04-06

Several related and complementary theoretical frameworks have been proposed to explain the existence of prosocial behavior, despite its potential fitness cost to the individual. These include kin selection theory, proposing that organisms have a propensity to help those to whom they are genetically related, and reciprocity, referring to the benefit of being prosocial, depending on past and future mutual interactions. A useful paradigm to examine prosociality is to compare mean levels of this behavior between monozygotic (MZ) and dizygotic (DZ) twins. Here, we examined the performance of 883 6.5-year-old twins (139 MZ and 302 DZ same-sex 6.5-year-old full twin pairs) in the Differential Productivity Task. In this task, the twins' behaviors were observed under two conditions: working for themselves vs. working for their co-twin. There were no significant differences between the performances of MZ and DZ twins in the prosocial condition of the task. Correlations within the twin dyads were significantly higher in MZ than DZ twins in the self-interested condition. However, similar MZ and DZ correlations were found in the prosocial condition, supporting the role of reciprocity in twins' prosociality towards each other. © 2018 John Wiley & Sons Ltd.

Heritability and confirmation of genetic association studies for childhood asthma in twins.

Science.gov (United States)

Ullemar, V; Magnusson, P K E; Lundholm, C; Zettergren, A; Melén, E; Lichtenstein, P; Almqvist, C

2016-02-01

Although the genetics of asthma has been extensively studied using both quantitative and molecular genetic analysis methods, both approaches lack studies specific to the childhood phenotype and including other allergic diseases. This study aimed to give specific estimates for the heritability of childhood asthma and other allergic diseases, to attempt to replicate findings from genomewide association studies (GWAS) for childhood asthma and to test the same variants against other allergic diseases. In a cohort of 25 306 Swedish twins aged 9 or 12 years, data on asthma were available from parental interviews and population-based registers. The interviews also inquired about wheeze, hay fever, eczema, and food allergy. Through structural equation modeling, the heritability of all phenotypes was calculated. A subset of 10 075 twins was genotyped for 16 single nucleotide polymorphisms (SNPs) selected from previous GWAS; these were first tested for association with asthma and significant findings also against the other allergic diseases. The heritability of any childhood asthma was 0.82 (95% CI 0.79-0.85). For the other allergic diseases, the range was approximately 0.60-0.80. Associations for six SNPs with asthma were replicated, including rs2305480 in the GSDMB gene (OR 0.80, 95% CI 0.74-0.86, P = 1.5*10(-8) ; other significant associations all below P = 3.5*10(-4) ). Of these, only rs3771180 in IL1RL1 was associated with any other allergic disease (for hay fever, OR 0.64, 95% CI 0.53-0.77, P = 2.5*10(-6) ). Asthma and allergic diseases of childhood are highly heritable, and these high-risk genetic variants associated specifically with childhood asthma, except for one SNP shared with hay fever. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Genetics of callous-unemotional behavior in children.

Directory of Open Access Journals (Sweden)

Essi Viding

Full Text Available Callous-unemotional behavior (CU is currently under consideration as a subtyping index for conduct disorder diagnosis. Twin studies routinely estimate the heritability of CU as greater than 50%. It is now possible to estimate genetic influence using DNA alone from samples of unrelated individuals, not relying on the assumptions of the twin method. Here we use this new DNA method (implemented in a software package called Genome-wide Complex Trait Analysis, GCTA for the first time to estimate genetic influence on CU. We also report the first genome-wide association (GWA study of CU as a quantitative trait. We compare these DNA results to those from twin analyses using the same measure and the same community sample of 2,930 children rated by their teachers at ages 7, 9 and 12. GCTA estimates of heritability were near zero, even though twin analysis of CU in this sample confirmed the high heritability of CU reported in the literature, and even though GCTA estimates of heritability were substantial for cognitive and anthropological traits in this sample. No significant associations were found in GWA analysis, which, like GCTA, only detects additive effects of common DNA variants. The phrase 'missing heritability' was coined to refer to the gap between variance associated with DNA variants identified in GWA studies versus twin study heritability. However, GCTA heritability, not twin study heritability, is the ceiling for GWA studies because both GCTA and GWA are limited to the overall additive effects of common DNA variants, whereas twin studies are not. This GCTA ceiling is very low for CU in our study, despite its high twin study heritability estimate. The gap between GCTA and twin study heritabilities will make it challenging to identify genes responsible for the heritability of CU.

Deformation twinning in irradiated ferritic/martensitic steels

Science.gov (United States)

Wang, K.; Dai, Y.; Spätig, P.

2018-04-01

Two different ferritic/martensitic steels were tensile tested to gain insight into the mechanisms of embrittlement induced by the combined effects of displacement damage and helium after proton/neutron irradiation in SINQ, the Swiss spallation neutron source. The irradiation conditions were in the range: 15.8-19.8 dpa (displacement per atom) with 1370-1750 appm He at 245-300 °C. All the samples fractured in brittle mode with intergranular or cleavage fracture surfaces when tested at room temperature (RT) or 300 °C. After tensile test, transmission electron microscopy (TEM) was employed to investigate the deformation microstructures. TEM-lamella samples were extracted directly below the intergranular fracture surfaces or cleavage surfaces by using the focused ion beam technique. Deformation twinning was observed in irradiated specimens at high irradiation dose. Only twins with {112} plane were observed in all of the samples. The average thickness of twins is about 40 nm. Twins initiated at the fracture surface, became gradually thinner with distance away from the fracture surface and finally stopped in the matrix. Novel features such as twin-precipitate interactions, twin-grain boundary and/or twin-lath boundary interactions were observed. Twinning bands were seen to be arrested by grain boundaries or large precipitates, but could penetrate martensitic lath boundaries. Unlike the case of defect free channels, small defect-clusters, dislocation loops and dense small helium bubbles were observed inside twins.

Whole exome sequencing identifies novel genes for fetal hemoglobin response to hydroxyurea in children with sickle cell anemia.

Science.gov (United States)

Sheehan, Vivien A; Crosby, Jacy R; Sabo, Aniko; Mortier, Nicole A; Howard, Thad A; Muzny, Donna M; Dugan-Perez, Shannon; Aygun, Banu; Nottage, Kerri A; Boerwinkle, Eric; Gibbs, Richard A; Ware, Russell E; Flanagan, Jonathan M

2014-01-01

Hydroxyurea has proven efficacy in children and adults with sickle cell anemia (SCA), but with considerable inter-individual variability in the amount of fetal hemoglobin (HbF) produced. Sibling and twin studies indicate that some of that drug response variation is heritable. To test the hypothesis that genetic modifiers influence pharmacological induction of HbF, we investigated phenotype-genotype associations using whole exome sequencing of children with SCA treated prospectively with hydroxyurea to maximum tolerated dose (MTD). We analyzed 171 unrelated patients enrolled in two prospective clinical trials, all treated with dose escalation to MTD. We examined two MTD drug response phenotypes: HbF (final %HbF minus baseline %HbF), and final %HbF. Analyzing individual genetic variants, we identified multiple low frequency and common variants associated with HbF induction by hydroxyurea. A validation cohort of 130 pediatric sickle cell patients treated to MTD with hydroxyurea was genotyped for 13 non-synonymous variants with the strongest association with HbF response to hydroxyurea in the discovery cohort. A coding variant in Spalt-like transcription factor, or SALL2, was associated with higher final HbF in this second independent replication sample and SALL2 represents an outstanding novel candidate gene for further investigation. These findings may help focus future functional studies and provide new insights into the pharmacological HbF upregulation by hydroxyurea in patients with SCA.

Roentgeno-cephalometric analysis on the twin

Energy Technology Data Exchange (ETDEWEB)

Choi, Hi Sup; Ahn, Hyung Kyu [College of Dentistry, Seoul National University, Seoul (Korea, Republic of)

1972-11-15

The purpose of this investigation can be sought for studying varients between twin by the cephalometric roentgenog raphic technics. The author have applied Down's, Bjork and Sakamoto's technic and measured in various angulations and length of cephalometric points. The results are as follows; 1. No significantly different data were found between twin. 2. There was no differences between normality and twin.

Exome Sequencing Identifies a Missense Variant in EFEMP1 Co-Segregating in a Family with Autosomal Dominant Primary Open-Angle Glaucoma.

Directory of Open Access Journals (Sweden)

Donna S Mackay

Full Text Available Primary open-angle glaucoma (POAG is a clinically important and genetically heterogeneous cause of progressive vision loss as a result of retinal ganglion cell death. Here we have utilized trio-based, whole-exome sequencing to identify the genetic defect underlying an autosomal dominant form of adult-onset POAG segregating in an African-American family. Exome sequencing identified a novel missense variant (c.418C>T, p.Arg140Trp in exon-5 of the gene coding for epidermal growth factor (EGF containing fibulin-like extracellular matrix protein 1 (EFEMP1 that co-segregated with disease in the family. Linkage and haplotype analyses with microsatellite markers indicated that the disease interval overlapped a known POAG locus (GLC1H on chromosome 2p. The p.Arg140Trp substitution was predicted in silico to have damaging effects on protein function and transient expression studies in cultured cells revealed that the Trp140-mutant protein exhibited increased intracellular accumulation compared with wild-type EFEMP1. In situ hybridization of the mouse eye with oligonucleotide probes detected the highest levels of EFEMP1 transcripts in the ciliary body, cornea, inner nuclear layer of the retina, and the optic nerve head. The recent finding that a common variant near EFEMP1 was associated with optic nerve-head morphology supports the possibility that the EFEMP1 variant identified in this POAG family may be pathogenic.

Twin-twin transfusion syndrome: cerebral ischemia is not the only fetal MR imaging finding

Energy Technology Data Exchange (ETDEWEB)

Kline-Fath, Beth M. [University of Cincinnati Medical Center, Department of Radiology, Cincinnati Children' s Hospital Medical Center, Cincinnati, OH (United States); Cincinnati Children' s Hospital, Department of Radiology, Cincinnati, OH (United States); Calvo-Garcia, Maria A.; O' Hara, Sara M.; Racadio, Judy M. [University of Cincinnati Medical Center, Department of Radiology, Cincinnati Children' s Hospital Medical Center, Cincinnati, OH (United States); Crombleholme, Timothy M. [University of Cincinnati Medical Center, Department of Surgery, Cincinnati Children' s Hospital Medical Center, Cincinnati, OH (United States)

2007-01-15

Twin-twin transfusion syndrome (TTTS) is a complication of monochorionic/diamniotic twin pregnancies. An imbalance of blood flow occurs through placental anastomoses, causing potentially significant morbidity and mortality in both twins. Although the sonographic findings of TTTS are well documented, we believe that MR imaging is a valuable adjunct. We describe the fetal MR imaging findings associated with TTTS. From 2003 to 2005, 37 consecutive MR imaging studies were performed on multiple-gestation pregnancies. Of the 37, 25 were consistent with TTTS, correlated and confirmed by sonographic criteria. MR fetal abnormalities were documented. Cerebral ischemia, which could not be demonstrated by sonography, was delineated well by MR imaging. New findings noted on fetal MR imaging were enlargement of cerebral venous sinuses in both twins, dilatation of the renal collecting system in the recipient, lung lesions in the recipient and cerebral malformations in the donor. MR imaging is an important adjunct in TTTS imaging. Its benefit over sonography is its clear definition of cerebral pathology, which is important for intervention and counseling. The new findings, particularly in the urinary tract and cerebral venous sinuses, also help support the diagnosis of TTTS and might reveal additional consequences of the altered hemodynamics that occur in TTTS. (orig.)

Twin-twin transfusion syndrome: cerebral ischemia is not the only fetal MR imaging finding

International Nuclear Information System (INIS)

Kline-Fath, Beth M.; Calvo-Garcia, Maria A.; O'Hara, Sara M.; Racadio, Judy M.; Crombleholme, Timothy M.

2007-01-01

Twin-twin transfusion syndrome (TTTS) is a complication of monochorionic/diamniotic twin pregnancies. An imbalance of blood flow occurs through placental anastomoses, causing potentially significant morbidity and mortality in both twins. Although the sonographic findings of TTTS are well documented, we believe that MR imaging is a valuable adjunct. We describe the fetal MR imaging findings associated with TTTS. From 2003 to 2005, 37 consecutive MR imaging studies were performed on multiple-gestation pregnancies. Of the 37, 25 were consistent with TTTS, correlated and confirmed by sonographic criteria. MR fetal abnormalities were documented. Cerebral ischemia, which could not be demonstrated by sonography, was delineated well by MR imaging. New findings noted on fetal MR imaging were enlargement of cerebral venous sinuses in both twins, dilatation of the renal collecting system in the recipient, lung lesions in the recipient and cerebral malformations in the donor. MR imaging is an important adjunct in TTTS imaging. Its benefit over sonography is its clear definition of cerebral pathology, which is important for intervention and counseling. The new findings, particularly in the urinary tract and cerebral venous sinuses, also help support the diagnosis of TTTS and might reveal additional consequences of the altered hemodynamics that occur in TTTS. (orig.)

Non-random X chromosome inactivation in an affected twin in a monozygotic twin pair discordant for Wiedemann-Beckwith syndrome

Energy Technology Data Exchange (ETDEWEB)

Oestavik, R.E.; Eiklid, K.; Oerstavik, K.H. [Ulleval Univ. Hospital, Oslo (Norway)] [and others

1995-03-27

Wiedemann-Beckwith syndrome (WBS) is a syndrome including exomphalos, macroglossia, and generalized overgrowth. The locus has been assigned to 11p15, and genomic imprinting may play a part in the expression of one or more genes involved. Most cases are sporadic. An excess of female monozygotic twins discordant for WBS have been reported, and it has been proposed that this excess could be related to the process of X chromosome inactivation. We have therefore studied X chromosome inactivation in 13-year-old monozygotic twin girls who were discordant for WBS. In addition, both twins had Tourette syndrome. The twins were monochorionic and therefore the result of a late twinning process. This has also been the case in previously reported discordant twin pairs with information on placentation. X chromosome inactivation was determined in DNA from peripheral blood cells by PCR analysis at the androgen receptor locus. The affected twin had a completely skewed X inactivation, where the paternal allele was on the active X chromosome in all cells. The unaffected twin had a moderately skewed X inactivation in the same direction, whereas the mother had a random pattern. Further studies are necessary to establish a possible association between the expression of WBS and X chromosome inactivation. 18 refs., 2 figs., 1 tab.

Twin pregnancy possibly associated with high semen quality

DEFF Research Database (Denmark)

Asklund, Camilla; Jensen, Tina Kold; Jørgensen, Niels

2007-01-01

BACKGROUND: Recent studies found an association between a long waiting time to pregnancy (TTP) and reduced probability of twinning and a reduced dizygotic (DZ) twinning rate in subfertile men. However, it remains unsolved whether semen quality is associated with twin offspring. We therefore studied...... the semen quality in a group of fathers of naturally conceived twins. METHODS: In this study, 37 fathers of DZ twins and 15 fathers of monozygotic (MZ) twins participated, and 349 normal fertile men served as a reference group. All men delivered a semen sample, underwent a physical examination and completed...... points higher than the reference group (P semen quality than the reference group, which supports...

Higher Rates of DZ Twinning in a Twenty-First Century Birth Cohort.

Science.gov (United States)

Rhea, Sally Ann; Corley, Robin P; Heath, Andrew C; Iacono, William G; Neale, Michael C; Hewitt, John K

2017-09-01

The Colorado Twin Registry is a population based registry initiated in 1984 with the involvement of the Colorado Department of Health, Division of Vital Statistics. Recruitment includes birth cohorts several years prior to 1984 and all subsequent years. As part of a recent evaluation of Colorado birth records for the years 2006 through 2008 we became aware of a shifting trend in the proportion of MZ and DZ twins in the Colorado population. Historically (Bulmer 1970 The biology of twinning in man, Clarendon, Oxford) we have expected a 1/3, 1/3, 1/3 ratio of MZ, same-sex DZ and opposite sex DZ twins in Caucasian populations. An excess of MZ pairs in most studies was assumed to be due to selection bias. Somewhat more recently, Hur et al.(1995 Behav Genet 25, 337-340) provided evidence that the DZ twinning rate was falling and that therefore selection bias was not the reason for higher MZ enrollment in most twin studies. They suggested that twin researchers might consider strategies to over-enroll DZ pairs to maximize statistical power. In contrast, we now find that of the 3217 twin births in Colorado from 2006 to 2008 with identified sex information the MZ rate is estimated at only 22%, and we have corroborating reports from other states of similar estimates. These were calculated applying Weinberg's rule which assumes an equal birth rate for same sex and opposite sex DZ pairs so that the proportion of MZ in a sample is the proportion of same sex (MM + FF) minus the proportion of opposite-sex (MF, FM). We explore factors, such as an increase in the proportion of non-Caucasian parents and an increase in average maternal age, which may contribute to this shift.

Bilateral Norrie's disease in identical twins.

OpenAIRE

Sukumaran, K

1991-01-01

A case of Norrie's disease in an identical twins is reported. No positive family history was obtained. The couple had no other children. The older of the twins died at the age of 9 months of uncertain cause. To the best of my knowledge this is the first case of Norrie's disease reported in Malaysia. And its occurrence in an identical twins is very rare.

Dental twinning anomalies: the nomenclature enigma.

Science.gov (United States)

Killian, C M; Croll, T P

1990-07-01

Dental twinning results from abnormal events in the embryologic development of teeth. This paper describes the impossibility of assigning precise diagnostic terms, such as germination, fusion, macrodontia, and concrescence, to dental twinning anomalies because the entire course of odontogenesis cannot be witnessed. Traditional nomenclature is reviewed and seven cases that exemplify the principle are presented. Modification of nomenclature to describe dental twinning defects is suggested.

Problem in twin pregnancy: Findings of prenatal sonography and autopsy

International Nuclear Information System (INIS)

Kim, Jeong Ah; Cho, Jeong Yeon; Song, Mi Jin; Min, Jee Yeon; Lee, Young Ho; Lee, Hak Jong; Chun, Yi Kyeong; Kim, Yee Jeong; Hong, Sung Ran

2001-01-01

Multifetal gestations are high risk pregnancies with higher perinatal morbidity and mortality. Multifetal gestations are subject to unique complications including conjoined twins, twin-to-twin transfusion syndrome (TTTS), acardiac twins, twin embization of co-twin demise and heterotopic pregnancies. Prenatal sonographic diagnosis of types and complications of multifetal gestations is important for antenatal care and prediction of fetal outcome. This study was performed to present the prenatal ultrasonographic findings and pathologic findings of the unique complications of twin pregnancy. Acardia is a lethal anomaly occurring in 1% of monozygotic twin. The acardiac twin has a parasitic existence and depends on the donor (pump) twin for its blood supply via placental anastomoses and retrograde perfusion of umbilical cord. This twin reversed arterial perfusion (TRAP) sequence is a most extreme manifestation on the TTTS. Doppler verification reversed flow in umbilical cord of the acardiac twin confirms the diagnosis.

Anencephaly with incomplete twinning (diprosopus).

Science.gov (United States)

Riccardi, V M; Bergmann, C A

1977-10-01

A case of diprosopus with anencephaly is presented. It is suggested that such concurrence of neural tube defects and incomplete twinning corroborates the notion that a single pathogenetic mechanism may be common to both neural tube defects and monozygotic twinning.

Targeted Resequencing and Functional Testing Identifies Low-Frequency Missense Variants in the Gene Encoding GARP as Significant Contributors to Atopic Dermatitis Risk.

Science.gov (United States)

Manz, Judith; Rodríguez, Elke; ElSharawy, Abdou; Oesau, Eva-Maria; Petersen, Britt-Sabina; Baurecht, Hansjörg; Mayr, Gabriele; Weber, Susanne; Harder, Jürgen; Reischl, Eva; Schwarz, Agatha; Novak, Natalija; Franke, Andre; Weidinger, Stephan

2016-12-01

Gene-mapping studies have consistently identified a susceptibility locus for atopic dermatitis and other inflammatory diseases on chromosome band 11q13.5, with the strongest association observed for a common variant located in an intergenic region between the two annotated genes C11orf30 and LRRC32. Using a targeted resequencing approach we identified low-frequency and rare missense mutations within the LRRC32 gene encoding the protein GARP, a receptor on activated regulatory T cells that binds latent transforming growth factor-β. Subsequent association testing in more than 2,000 atopic dermatitis patients and 2,000 control subjects showed a significant excess of these LRRC32 variants in individuals with atopic dermatitis. Structural protein modeling and bioinformatic analysis predicted a disruption of protein transport upon these variants, and overexpression assays in CD4 + CD25 - T cells showed a significant reduction in surface expression of the mutated protein. Consistently, flow cytometric (FACS) analyses of different T-cell subtypes obtained from atopic dermatitis patients showed a significantly reduced surface expression of GARP and a reduced conversion of CD4 + CD25 - T cells into regulatory T cells, along with lower expression of latency-associated protein upon stimulation in carriers of the LRRC32 A407T variant. These results link inherited disturbances of transforming growth factor-β signaling with atopic dermatitis risk. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Prenatal x-ray and childhood cancer in twins

International Nuclear Information System (INIS)

Harvey, E.B.

1983-01-01

In order to evaluate the causal nature of the relationship between prenatal x-ray exposure and childhood cancer, a case control study was conducted in a population of over 32,000 twins born in the state of Connecticut from 1930-1969 and followed to age 15. Thirty-two incident cancer cases were identified by linking the Connecticut Twin and Tumor registries. Each case was matched with four controls on year of birth, sex, race, and survival. Prenatal x-ray information as well as reproductive, delivery and birth data were obtained from the hospital of birth, the physician providing prenatal care, private radiology groups and interviews with hospital staff. The case control study which obtained exposure information on selected subjects found an increased risk of childhood cancer from prenatal x-ray exposure. The risk associated with radiation exposure was elevated in the following subcategories: mother with history of pregnancy loss, a gravity greater than 1, under 30 years of age, and twins weighing five pounds or more at birth. The results, though based on small numbers, strengthen the association between prenatal x-ray exposure and childhood cancer

Anorexia and Bulimia Nervosa in Same-Sex and Opposite-Sex Twins : Lack of Association With Twin Type in a Nationwide Study of Finnish Twins

NARCIS (Netherlands)

Raevuori, Anu; Kaprio, Jaakko; Hoek, Hans W.; Sihvola, Elina; Rissanen, Aila; Keski-Rahkonen, Anna

2008-01-01

Objective: The authors tested the hypothesis that either prenatal feminization or masculinization hormone influences in utero or later socialization affects the risk for anorexia and bulimia nervosa and disordered eating in members of opposite-sex twin pairs. Method: Finnish twins (N=2,426 women,

Neurological impairment in a surviving twin following intrauterine fetal demise of the co-twin: a case study.

Science.gov (United States)

Forrester, K R; Keegan, K M; Schmidt, J W

2013-01-01

It has been established that twin pregnancies are at an increased risk for complications, including the risk of morbidity or mortality for one or both of the infants. Cerebral palsy and other associated neurological deficits also occur at higher rates in twin pregnancies. This report examines two cases of intrauterine demise of one twin with subsequent survival of the co-twin. In both cases, the surviving infant suffered significant neurological sequelae. Impairments observed in these two cases include multicystic encephalomalacia and periventricular leukomalacia as well as the subsequent development of cerebral palsy. This case study explores the predisposing factors, incidence, pathophysiology, consequences, and future research implications of these findings.

Germline Variants of Prostate Cancer in Japanese Families.

Directory of Open Access Journals (Sweden)

Takahide Hayano

Full Text Available Prostate cancer (PC is the second most common cancer in men. Family history is the major risk factor for PC. Only two susceptibility genes were identified in PC, BRCA2 and HOXB13. A comprehensive search of germline variants for patients with PC has not been reported in Japanese families. In this study, we conducted exome sequencing followed by Sanger sequencing to explore responsible germline variants in 140 Japanese patients with PC from 66 families. In addition to known susceptibility genes, BRCA2 and HOXB13, we identified TRRAP variants in a mutually exclusive manner in seven large PC families (three or four patients per family. We also found shared variants of BRCA2, HOXB13, and TRRAP from 59 additional small PC families (two patients per family. We identified two deleterious HOXB13 variants (F127C and G132E. Further exploration of the shared variants in rest of the families revealed deleterious variants of the so-called cancer genes (ATP1A1, BRIP1, FANCA, FGFR3, FLT3, HOXD11, MUTYH, PDGFRA, SMARCA4, and TCF3. The germline variant profile provides a new insight to clarify the genetic etiology and heterogeneity of PC among Japanese men.

Hypertensive disorders in twin pregnancy

NARCIS (Netherlands)

J.G. Santema (Job); E. Koppelaar (Elin); H.C.S. Wallenburg (Henk)

1995-01-01

textabstractObjective: To compare the incidence and severity of pregnancy-induced hypertensive disorders in twin pregnancy and in singleton gestation. Study design: Case-control study in the setting of a University Hospital. Each pregnancy of a consecutive series of 187 twin pregnancies attending

[Panhypopituitarism in one identical twin: the effect of hormone replacement].

Science.gov (United States)

Del Canho, Harrij; van Alfen-van der Velden, Janiëlle; del Canho, Riwka; Otten, Barto

2011-01-01

Panhypopituitarism in childhood is rare. It is even rarer if the disorder appears in a boy with an identical but healthy twin brother. In such a patient it is useful to study the consequences of the hormone disorder and the effect of hormone replacement. A 6-year-old boy saw a paediatrician because of short stature. He was much shorter than his identical twin brother and he had more abdominal fat mass and a smaller penis. Laboratory tests identified hypothyroidism of central origin, in combination with hypocortisolism and growth hormone deficiency. Hormonal replacement resulted in an improvement in growth rate. At the age of 15 years, testosterone therapy was introduced because puberty had not occurred and his growth rate was low. Finally the patient grew a few centimetres taller than his twin brother. In the first year of life, panhypopituitarism has no negative consequences for growth. After this point, growth is clearly delayed. With sufficient replacement growth can completely catch up.

Concordance for multiple sclerosis in Danish twins

DEFF Research Database (Denmark)

Hansen, T; Skytthe, Axel; Stenager, Egon

2005-01-01

The occurrence of multiple sclerosis (MS) in twins has not previously been studied in complete nationwide data sets. The existence of almost complete MS and twin registries in Denmark ensures that essentially unbiased samples of MS cases among twins can be obtained. In this population-based study...

Numerical Simulation of Twin Nozzle Injectors

OpenAIRE

Milak, Dino

2015-01-01

Fuel injectors for marine applications have traditionally utilized nozzles with symmetric equispaced orifice configuration. But in light of the new marine emission legislations the twin nozzle concept has arisen. The twin nozzle differs from the conventional configuration by utilizing two closely spaced orifices to substitute each orifice in the conventional nozzle. Injector manufacturers regard twin nozzle injectors as a promising approach to facilitate stable spray patterns independent of t...

Socio-psycho-historical observation on the twin. Sampling methods and case study of the atomic bomb exposed twins

Energy Technology Data Exchange (ETDEWEB)

Watanabe, S; Satow, Y; Ueoka, Hiroshi; Munaka, M; Kurihara, M [Hiroshima Univ. (Japan). Research Inst. for Nuclear Medicine and Biology

1980-07-01

The so-called ''twin control study'', mainly on the monozygotic twins one of which was A-bomb exposed and the other was non-exposed were carried out. Sampling was conducted utilizing the materials as follows: 1) The survey on casualities of A-bomb exposed families in Hiroshima which was undertaken in 1946. 2) The survey of A-bomb survivors in 1965. 3) A-bomb exposed family survey conducted between 1973 to 1975. 4) Investigations of A-bomb victims exposed in the proximal areas from the hypocenter. From the above mentioned materials 470 pairs were selected, of which 220 were exposed. Among them 172 pairs were twins of the same sex. Female and male pair were also employed. In one case they were exposed, while the others were nonexposed. Two pairs were examined under the following methods: 1) Depth interview to ascertain familial casualities with reference to the family life cycle. 2) Socio-historical research. 3) Motoaki's Jinkaku Shindan Kensa (Modified Rorschach test by H. Motoaki), and T.A.T. test. Results obtained were summarized as follows: 1) Both pairs of twins were of similar appearance and personality traits, and had a strong feeling of companionship for each other. 2) In family relationships, the persons studied were very conscious of the role expectations of elder and younger siblings in the twin pairs. 3) Through depth interviews and projective tests, A-bomb exposed pairs still showed deep psychological stresses, resulting from the A-bomb disaster. 4) Both among the exposed twins and within the nonexposed control group twin siblings had a close feeling of companionship for each other. However, nonexposed twins could not understand the psychological experience of twins who had been subjected to the atomic disaster.

[Association between obesity and DNA methylation among the 7-16 year-old twins].

Science.gov (United States)

Li, C X; Gao, Y; Gao, W J; Yu, C Q; Lyu, J; Lyu, R R; Duan, J L; Sun, Y; Guo, X H; Wang, S F; Zhou, B; Wang, G; Cao, W H; Li, L M

2018-04-10

Objective: On whole-genome scale, we tried to explore the correlation between obesity-related traits and DNA methylation sites, based on discordant monozygotic twin pairs. Methods: A total of 90 pairs of 6-17 year-old twins were recruited in Chaoyang district, Yanqing district and Fangshan district in Beijing in 2016. Information on twins was gathered through a self-designed questionnaire and results: from physical examination, including height, weight and waist circumference of the subjects under study. DNA methylation detection was chosen on the Illumina Human Methylation EPIC BeadChip. R 3.3.1 language was used to read the DNA methylation signal under quality control on samples and probes. Ebayes function of empirical Bayes paired moderated t -test was used to identify the differential methylated CpG sites (DMCs). VarFit function of empirical Bayes paired moderated Levene test was used to identify the differentially variables CpG sits (DVCs) in obese and normal groups. Results According to the obesity discordance criteria, we collected 23 pairs of twins (age range 7 to 16 years), including 12 male pairs. A total of 817 471 qualified CpG loci were included in the genome-wide correlation analysis. According to the significance level of FDR set as obesity traits. After multiple testing corrections, no positive sites were found to have associated with obesity. However, results from the correlation analysis demonstrated sites cg05684382 (chr: 12) and cg26188191 (chr: 16) might have played a role in the development of obesity. This study provides a methodologic reference for the studies on discordance twins related problems.

Twinning of Polymer Crystals Suppressed by Entropy

Directory of Open Access Journals (Sweden)

Nikos Ch. Karayiannis

2014-09-01

Full Text Available We propose an entropic argument as partial explanation of the observed scarcity of twinned structures in crystalline samples of synthetic organic polymeric materials. Polymeric molecules possess a much larger number of conformational degrees of freedom than low molecular weight substances. The preferred conformations of polymer chains in the bulk of a single crystal are often incompatible with the conformations imposed by the symmetry of a growth twin, both at the composition surfaces and in the twin axis. We calculate the differences in conformational entropy between chains in single crystals and chains in twinned crystals, and find that the reduction in chain conformational entropy in the twin is sufficient to make the single crystal the stable thermodynamic phase. The formation of cyclic twins in molecular dynamics simulations of chains of hard spheres must thus be attributed to kinetic factors. In more realistic polymers this entropic contribution to the free energy can be canceled or dominated by nonbonded and torsional energetics.

Genome-Wide Association Study Identifies Risk Variants for Lichen Planus in Patients With Hepatitis C Virus Infection.

Science.gov (United States)

Nagao, Yumiko; Nishida, Nao; Toyo-Oka, Licht; Kawaguchi, Atsushi; Amoroso, Antonio; Carrozzo, Marco; Sata, Michio; Mizokami, Masashi; Tokunaga, Katsushi; Tanaka, Yasuhito

2017-06-01

There is a close relationship between hepatitis C virus (HCV) infection and lichen planus, a chronic inflammatory mucocutaneous disease. We performed a genome-wide association study (GWAS) to identify genetic variants associated with HCV-related lichen planus. We conducted a GWAS of 261 patients with HCV infection treated at a tertiary medical center in Japan from October 2007 through January 2013; a total of 71 had lichen planus and 190 had normal oral mucosa. We validated our findings in a GWAS of 38 patients with HCV-associated lichen planus and 7 HCV-infected patients with normal oral mucosa treated at a medical center in Italy. Single-nucleotide polymorphisms in NRP2 (rs884000) and IGFBP4 (rs538399) were associated with risk of HCV-associated lichen planus (P lichen planus. The odds ratios for the minor alleles of rs884000, rs538399, and rs9461799 were 3.25 (95% confidence interval, 1.95-5.41), 0.40 (95% confidence interval, 0.25-0.63), and 2.15 (95% confidence interval, 1.41-3.28), respectively. In a GWAS of Japanese patients with HCV infection, we replicated associations between previously reported polymorphisms in HLA class II genes and risk for lichen planus. We also identified single-nucleotide polymorphisms in NRP2 and IGFBP4 loci that increase and reduce risk of lichen planus, respectively. These genetic variants might be used to identify patients with HCV infection who are at risk for lichen planus. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

Twin specific risk factors in primary school achievements.

Science.gov (United States)

de Zeeuw, Eveline L; van Beijsterveldt, Catherina E M; de Geus, Eco J C; Boomsma, Dorret I

2012-02-01

The main aim of this study was to examine twin specific risk factors that influence educational achievement in primary school. We included prenatal factors that are not unique to twins, except for zygosity, but show a higher prevalence in twins than in singletons. In addition, educational achievement was compared between twins and their nontwin siblings in a within-family design. Data were obtained from parents and teachers of approximately 10,000 twins and their nontwin siblings registered with the Netherlands Twin Register. Teachers rated the proficiency of the children on arithmetic, language, reading, and physical education, and reported a national educational achievement test score (CITO). Structural equation modeling showed that gestational age, birth weight, and sex were significant predictors of educational achievement, even after correction for socioeconomic status. Mode of delivery and zygosity did not have an effect, while parental age only influenced arithmetic. Mode of conception, incubator time, and birth complications negatively affected achievement in physical education. The comparison of educational achievement of twins and singletons showed significantly lower ratings on arithmetic, reading, and language in twins, compared to their older siblings, but not compared to their younger siblings. Low gestational age and low birth weight were the most important risk factors for lower educational achievement of twins in primary school. It seems that the differences observed between twins and their nontwin siblings in educational achievement can largely be explained by birth order within the family.

Laying the ghost of twin paradox

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Popović Marko

2009-01-01

Full Text Available Someone's true age is not written in his ID, but in his biomarkers. Aging process is not caused by time passing, but by thermodynamically laws. Entropy, extent of metabolic reaction, and temperature are Lorentz invariant, so these facts make twin paradox impossible because there is no way for one twin to age slower than the other even if the time in his frame is dilated. Entropy is the function of state, not time. So as much as standard thermodynamics concerns, the path between two points in space is equivalent to the path between two states. Whether the point B is reached by moving faster using the longer way (with time dilatation, or slower by using shortcut (without time dilatation, the state of the system after completing the road should be the same. This is supported by the fact that when two twins reach the same space-time point (point B in which the state parameters are the same. If we use entropy as an age parameter, then both twins have the same entropy value and are exactly the same biological age. Therefore, the twin paradox is a logical mistake based on wrong first premise. Bergson symmetry is not necessary any more to explain the impossibility of twin paradox.

The Concordance and Heritability of Type 2 Diabetes in 34,166 Twin Pairs From International Twin Registers

DEFF Research Database (Denmark)

Willemsen, G.; Ward, K. J.; Bell, C. G.

2015-01-01

studies worldwide need to pool their resources. The Discordant Twin (DISCOTWIN) consortium was established for this goal. Here, we describe the DISCOTWIN Consortium and present an analysis of type 2 diabetes (T2D) data in nearly 35,000 twin pairs. Seven twin cohorts from Europe (Denmark, Finland, Norway...... and medication use, fasting glucose and insulin measures, or medical records. The prevalence of T2D ranged from 2.6% to 12.3% across the cohorts depending on age, body mass index (BMI), and national diabetes prevalence. T2D discordance rate was lower for MZ (5.1%, range 2.9-11.2%) than for same-sex dizygotic (DZ......, the Netherlands, Spain, Sweden, and the United Kingdom) and one from Australia investigated the rate of discordance for T2D in same-sex twin pairs aged 45 years and older. Data were available for 34,166 same-sex twin pairs, of which 13,970 were MZ, with T2D diagnosis based on self-reported diagnosis...

Peak effect in twinned superconductors

International Nuclear Information System (INIS)

Larkin, A.I.; Marchetti, M.C.; Vinokur, V.M.

1995-01-01

A sharp maximum in the critical current J c as a function of temperature just below the melting point of the Abrikosov flux lattice has recently been observed in both low- and high-temperature superconductors. This peak effect is strongest in twinned crystals for fields aligned with the twin planes. We propose that this peak signals the breakdown of the collective pinning regime and the crossover to strong pinning of single vortices on the twin boundaries. This crossover is very sharp and can account for the steep drop of the differential resistivity observed in experiments. copyright 1995 The American Physical Society

Effect of twinning plane on superconductor magnetic properties

International Nuclear Information System (INIS)

Buzdin, A.I.; Kuptsov, D.A.

1989-01-01

Effect of twinning planes on pinning of the Abrikosov vortices in superconductors of the second order with the Ginsburg-Landau parameter, κ >> 1, is considered. The modified Ginsburg-Landau functional, where the effect of superconducting properties improvement near the twinning plane is taken into account by adding the additional δ-function component, is used to descibe superconductivity of twinning plane. Force of interaction of a vortex filament and the twinning plane is calculated. It is shown that in case of the twinning plane opaque to electrons, additional attractive force, being analogous to that occurring in the problem on the surface Been-Livingston barrier, affects the vortex filament. The results can explain anisotropy of vortex pinning observed in the periodic twinning structure in high-temperature superconductors

Twin Pregnancy with Gastroschisis in Both Twins

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Hui-Fen Kao

2007-12-01

Conclusion: The cause of gastroschisis is unknown, although possible exogenous causes have been studied. The diagnosis of gastroschisis in twin pregnancy is always in late gestation. Therefore, maternal serum alpha feto-protein screening and a detailed prenatal ultrasound evaluation are recommended in multifetal pregnancies.

A familial case of segregation of motor sensory neuropathy type 1B with multiple exostoses in monozygous twins

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V. P. Fedotov

2015-01-01

Full Text Available Hereditary motor-sensory neuropathy (MIM 118200 is a rare genetic variant of myelinopathy with autosomal-dominant type of inheritance. Multiple exostosis bones are signs of multiple exostoses chondrodysplasia, genetically heterogeneous form of systemic bone disease with an autosomal dominant mode of inheritance. The combination of two rare autosomal dominant diseases, affecting bone and peripheral nervous system in a pair of monozygotic twins and their father in one family, belongs to a unique clinical observations: since early childhood twins presented sharp reduction of the conduction velocity in all investigated motor nerves (>10 times together with multiple exostosis bone, confirmed by x-ray with a relatively benign course. Similar manifestations were detected in the patients father. DNA analysis confirmed the presence of 2 separate mutations in 2 different genes, с.389А>G/N gene MPZ and c.678С>А/N EXT2 gene that was inherited autosomal dominant manner, independently of each members of the same family.

Associations Between Fast-Food Consumption and Body Mass Index: A Cross-Sectional Study in Adult Twins.

Science.gov (United States)

Cohen-Cline, Hannah; Lau, Richard; Moudon, Anne V; Turkheimer, Eric; Duncan, Glen E

2015-08-01

Obesity is a substantial health problem in the United States, and is associated with many chronic diseases. Previous studies have linked poor dietary habits to obesity. This cross-sectional study aimed to identify the association between body mass index (BMI) and fast-food consumption among 669 same-sex adult twin pairs residing in the Puget Sound region around Seattle, Washington. We calculated twin-pair correlations for BMI and fast-food consumption. We next regressed BMI on fast-food consumption using generalized estimating equations (GEE), and finally estimated the within-pair difference in BMI associated with a difference in fast-food consumption, which controls for all potential genetic and environment characteristics shared between twins within a pair. Twin-pair correlations for fast-food consumption were similar for identical (monozygotic; MZ) and fraternal (dizygotic; DZ) twins, but were substantially higher in MZ than DZ twins for BMI. In the unadjusted GEE model, greater fast-food consumption was associated with larger BMI. For twin pairs overall, and for MZ twins, there was no association between within-pair differences in fast-food consumption and BMI in any model. In contrast, there was a significant association between within-pair differences in fast-food consumption and BMI among DZ twins, suggesting that genetic factors play a role in the observed association. Thus, although variance in fast-food consumption itself is largely driven by environmental factors, the overall association between this specific eating behavior and BMI is largely due to genetic factors.

Temperature dependence of work hardening in sparsely twinning zirconium

International Nuclear Information System (INIS)

Singh, Jaiveer; Mahesh, S.; Roy, Shomic; Kumar, Gulshan; Srivastava, D.; Dey, G.K.; Saibaba, N.; Samajdar, I.

2017-01-01

Fully recrystallized commercial Zirconium plates were subjected to uniaxial tension. Tests were conducted at different temperatures (123 K - 623 K) and along two plate directions. Both directions were nominally unfavorable for deformation twinning. The effect of the working temperature on crystallographic texture and in-grain misorientation development was insignificant. However, systematic variation in work hardening and in the area fraction and morphology of deformation twins was observed with temperature. At all temperatures, twinning was associated with significant near boundary mesoscopic shear, suggesting a possible linkage with twin nucleation. A binary tree based model of the polycrystal, which explicitly accounts for grain boundary accommodation and implements the phenomenological extended Voce hardening law, was implemented. This model could capture the measured stress-strain response and twin volume fractions accurately. Interestingly, slip and twin system hardness evolution permitted multiplicative decomposition into temperature-dependent, and accumulated strain-dependent parts. Furthermore, under conditions of relatively limited deformation twinning, the work hardening of the slip and twin systems followed two phenomenological laws proposed in the literature for non-twinning single-phase face centered cubic materials.

EBSD characterization of twinning in cold-rolled CP-Ti

International Nuclear Information System (INIS)

Li, X.; Duan, Y.L.; Xu, G.F.; Peng, X.Y.; Dai, C.; Zhang, L.G.; Li, Z.

2013-01-01

This work presents the use of a mechanical testing system and the electron backscatter diffraction technique to study the mechanical properties and twinning systems of cold-rolled commercial purity titanium, respectively. The dependence of twinning on the matrix orientation is analyzed by the distribution map of Schmid factor. The results showed that the commercial purity titanium experienced strong strain hardening and had excellent formability during rolling. Both the (112 ¯ 2) ¯ 3 ¯ > compressive twins and (101 ¯ 2) ¯ 1 ¯ > tensile twins were dependent on the matrix orientation. The Schmid factor of a grain influenced the activation of a particular twinning system. The specific rolling deformation of commercial purity titanium controlled the number and species of twinning systems and further changed the mechanical properties. - Highlights: • CP-Ti experienced strain hardening and had excellent formability. • Twins were dependent on the matrix orientation. • Schmid factor of a grain influenced the activation of a twinning system. • Rolling deformation controlled twinning systems and mechanical properties

Socio-psycho-historical observation on the twin

International Nuclear Information System (INIS)

Watanabe, Shoji; Satow, Yukio; Ueoka, Hiroshi; Munaka, Masaki; Kurihara, Minoru

1980-01-01

The so-called ''twin control study'', mainly on the monozygotic twins one of which was A-bomb exposed and the other was non-exposed were carried out. Sampling was conducted utilizing the materials as follows: 1) The survey on casualities of A-bomb exposed families in Hiroshima which was undertaken in 1946. 2) The survey of A-bomb survivors in 1965. 3) A-bomb exposed family survey conducted between 1973 to 1975. 4) Investigations of A-bomb victims exposed in the proximal areas from the hypocenter. From the above mentioned materials 470 pairs were selected, of which 220 were exposed. Among them 172 pairs were twins of the same sex. Female and male pair were also employed. In one case they were exposed, while the others were nonexposed. Two pairs were examined under the following methods: 1) Depth interview to ascertain familial casualities with reference to the family life cycle. 2) Socio-historical research. 3) Motoaki's Jinkaku Shindan Kensa (Modified Rorschach test by H. Motoaki), and T.A.T. test. Results obtained were summarized as follows: 1) Both pairs of twins were similar appearance, and also personality traits, and had a strong feeling of companionship for each other. 2) In family relationships, the persons studied were very conscious of the role expectations of elder and younger siblings in the twin pairs. 3) Through depth interview and projective test, A-bomb exposed pairs still showed deep psychological stresses, resulting from the A-bomb disaster. 4) Both among the exposed twins and within the nonexposed control group twin siblings had a close feeling of companionship for each other. However, nonexposed twins could not understand the psychological experience of twins who had been subjected to the atomic disaster. (author)

Hydride formation on deformation twin in zirconium alloy

Energy Technology Data Exchange (ETDEWEB)

Kim, Ju-Seong [Korea Atomic Energy Research Institute, 989-111 Daedeokdaero, Yuseong-gu, Daejeon, 305-353 (Korea, Republic of); Kim, Sung-Dae [Korea Institute of Material Science (KIMS), 797 Changwondaero, Changwon, Gyeongnam, 642-831 (Korea, Republic of); Yoon, Jonghun, E-mail: yooncsmd@gmail.com [Department of Mechanical Engineering, Hanyang University, 1271 Sa3-dong, Sangrok-gu, Ansan-si, Gyeonggi-do, 426-791 (Korea, Republic of)

2016-12-15

Hydrides deteriorate the mechanical properties of zirconium (Zr) alloys used in nuclear reactors. Intergranular hydrides that form along grain boundaries have been extensively studied due to their detrimental effects on cracking. However, it has been little concerns on formation of Zr hydrides correlated with deformation twins which is distinctive heterogeneous nucleation site in hexagonal close-packed metals. In this paper, the heterogeneous precipitation of Zr hydrides at the twin boundaries was visualized using transmission electron microscopy. It demonstrates that intragranular hydrides in the twinned region precipitates on the rotated habit plane by the twinning and intergranular hydrides precipitate along the coherent low energy twin boundaries independent of the conventional habit planes. Interestingly, dislocations around the twin boundaries play a substantial role in the nucleation of Zr hydrides by reducing the misfit strain energy.

New theory for crack-tip twinning in fcc metals

Science.gov (United States)

Andric, Predrag; Curtin, W. A.

2018-04-01

Dislocation emission from a crack tip is a necessary mechanism for crack tip blunting and toughening. In fcc metals under Mode I loading, a first partial dislocation is emitted, followed either by a trailing partial dislocation ("ductile" behaviour) or a twinning partial dislocation ("quasi-brittle"). The twinning tendency is usually estimated using the Tadmor and Hai extension of the Rice theory. Extensive molecular statics simulations reveal that the predictions of the critical stress intensity factor for crack tip twinning are always systematically lower (20-35%) than observed. Analyses of the energy change during nucleation reveal that twin partial emission is not accompanied by creation of a surface step while emission of the trailing partial creates a step. The absence of the step during twinning motivates a modified model for twinning nucleation that accounts for the fact that nucleation does not occur directly at the crack tip. Predictions of the modified theory are in excellent agreement with all simulations that show twinning. Emission of the trailing partial dislocation, including the step creation, is predicted using a model recently introduced to accurately predict the first partial emission and shows why twinning is preferred. A second mode of twinning is found wherein the crack first advances by cleavage and then emits the twinning partial at the new crack tip; this mode dominates for emission beyond the first twinning partial. These new theories resolve all the discrepancies between the Tadmor twinning analysis and simulations, and have various implications for fracture behaviour and transitions.

Cyclin-dependent Kinase 5: Novel role of gene variants identified in ADHD.

Science.gov (United States)

Maitra, Subhamita; Chatterjee, Mahasweta; Sinha, Swagata; Mukhopadhyay, Kanchan

2017-07-28

Cortical neuronal migration and formation of filamentous actin cytoskeleton, needed for development, normal cell growth and differentiation, are regulated by the cyclin-dependent kinase 5 (Cdk5). Attention deficit hyperactivity disorder (ADHD) is associated with delayed maturation of the brain and hence we hypothesized that cdk5 may have a role in ADHD. Eight functional CDK5 gene variants were analyzed in 848 Indo-Caucasoid individuals including 217 families with ADHD probands and 250 healthy volunteers. Only three variants, rs2069454, rs2069456 and rs2069459, predicted to affect transcription, were found to be bimorphic. Significant difference in rs2069456 "AC" genotype frequency was noticed in the probands, more specifically in the males. Family based analysis revealed over transmission of rs2069454 "C" and rs2069456 "A" to the probands. Quantitative trait analysis exhibited association of haplotypes with inattention, domain specific impulsivity, and behavioral problem, though no significant contribution was noticed on the age of onset of ADHD. Gene variants also showed significant association with cognitive function and co-morbidity. Probands having rs2069459 "TT" showed betterment during follow up. It may be inferred from this pilot study that CDK5 may affect ADHD etiology, possibly by attenuating synaptic neurotransmission and could be a useful target for therapeutic intervention.

Combinations of Genetic Variants Occurring Exclusively in Patients

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Erling Mellerup

Full Text Available In studies of polygenic disorders, scanning the genetic variants can be used to identify variant combinations. Combinations that are exclusively found in patients can be separated from those combinations occurring in control persons. Statistical analyses can be performed to determine whether the combinations that occur exclusively among patients are significantly associated with the investigated disorder. This research strategy has been applied in materials from various polygenic disorders, identifying clusters of patient-specific genetic variant combinations that are significant associated with the investigated disorders. Combinations from these clusters are found in the genomes of up to 55% of investigated patients, and are not present in the genomes of any control persons. Keywords: Genetic variants, Polygenic disorder, Combinations of genetic variants, Patient-specific combinations

Differences in Religiousness in Opposite-Sex and Same-Sex Twins in a Secular Society.

Science.gov (United States)

Ahrenfeldt, Linda J; Lindahl-Jacobsen, Rune; Möller, Sören; Christensen, Kaare; Hvidtjørn, Dorte; Hvidt, Niels Christian

2016-02-01

Sex differences in religion are well known, with females generally being more religious than males, and shared environmental factors have been suggested to have a large influence on religiousness. Twins from opposite-sex (OS) and same-sex (SS) pairs may differ because of a dissimilar psycho-social rearing environment and/or because of different exposures to hormones in utero. We hypothesized that OS females may display more masculine patterns of religiousness and, vice versa, that OS males may display more feminine patterns. We used a web-based survey conducted in Denmark, which is a secular society. The survey included 2,997 twins aged 20-40 years, identified through the population-based Danish Twin Registry. We applied la Cour and Hvidt's adaptation of Fishman's three conceptual dimensions of meaning: Cognition, Practice, and Importance, and we used Pargament's measure of religious coping (RCOPE) for the assessment of positive and negative religious coping patterns. Differences between OS and SS twins were investigated using logistic regression for each sex. The analyses were adjusted for dependence within twin pairs. No significant differences in religiousness and religious coping were found for OS and SS twins except that more OS than SS females were members of the Danish National Evangelical Lutheran Church and fewer OS than SS females were Catholic, Muslim, or belonged to other religious denominations. Moreover, OS males at age 12 had higher rates of church attendance than did SS males. This study did not provide evidence for masculinization of female twins with male co-twins with regard to religiousness. Nor did it show any significant differences between OS and SS males except from higher rates of church attendance in childhood among males with female co-twins.

Do assisted-reproduction twin pregnancies require additional antenatal care?

Science.gov (United States)

Jauniaux, E; Ben-Ami, I; Maymon, R

2013-02-01

Iatrogenic twinning has become the main side-effect assisted reproduction treatment. We have evaluated the evidence for additional care that assisted-reproduction twins may require compared with spontaneous twins. Misacarriages are increased in women with tubal problems and after specific treatments. Assisted-reproduction twin pregnancies complicated by a vanishing twin after 8 weeks have an increased risk of preterm delivery and of low and very low birthweight compared with singleton assisted-reproduction pregnancies. Monozygotic twin pregnancies occur at a higher rate after assisted reproduction treatment and are associated with a higher risk of perinatal complications. The incidence of placenta praevia and vasa praevia is increased in assisted-reproduction twin pregnancies. Large cohort studies do not indicate a higher rate of fetal congenital malformations in assisted-reproduction twins. Overall, assisted-reproduction twins in healthy women assisted-reproduction twins is only increased in women with a pre-existing medical condition such as hypertensive disorders and diabetes and most of these risks can be avoided with single-embryo transfer. Following the birth of the first IVF baby, rumours started to spread in both the medical literature and the media about the long-term health effects for children born following assisted reproduction treatment. However, after more than 30 years, the most common complications associated with IVF treatment remain indirect and technical such as the failure of treatment and ovarian hyperstimulation. Iatrogenic twinning has become the main side-effect of assisted reproduction treatment and the increasing number of twin pregnancies, in particular in older women, has generated numerous debates on the need for additional healthcare provision. In this review, we have evaluated the evidence for additional care that assisted-conception twin pregnancies may require compared with spontaneous twin pregnancies. Twin pregnancies are

Dichorionic Diamniotic Twin Pregnancy Discordant for Bladder Exstrophy

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William Tu

2009-01-01

Full Text Available A 38 year-old woman presented with a dichorionic diamniotic twin pregnancy at gestational age of 32 weeks concerning for an abdominal wall mass in one of the twins. Initial ultrasound evaluation was suspicious for an omphalocele, but the affected twin was found to have bladder exstrophy at birth. This illustrates the difficulties of accurate prenatal diagnosis of bladder exstrophy in a twin pregnancy at a late gestation.

A note on twin-singleton differences in asthma

DEFF Research Database (Denmark)

Thomsen, Simon Francis; Kyvik, Kirsten Ohm; Backer, Vibeke

2008-01-01

Twins constitute a valuable resource for genetic studies of asthma. However, critics argue that twins are 'special' in terms of prenatal environment and upbringing and therefore nonrepresentative. In respect to asthma a small range of studies report differential morbidity in twins compared...... with singletons. We review some of the possible explanations for these findings and conclude that results from twin studies of asthma can be extrapolated to the general population....

Epigenetic Epidemiology of Complex Diseases Using Twins

DEFF Research Database (Denmark)

Tan, Qihua

2013-01-01

through multiple epigenetic mechanisms. This paper reviews the new developments in using twins to study disease-related epigenetic alterations, links them to lifetime environmental exposure with a focus on the discordant twin design and proposes novel data-analytical approaches with the aim of promoting...... a more efficient use of twins in epigenetic studies of complex human diseases....

Twin Studies of Atopic Dermatitis

DEFF Research Database (Denmark)

Elmose, Camilla; Thomsen, Simon Francis

2015-01-01

Aim. The aim of this study was to conduct a systematic review of population-based twin studies of (a) the concordance and heritability of AD and (b) the relationship between AD and asthma and, furthermore, to reinterpret findings from previous twin studies in the light of the emerging knowledge a...

Receptor homodimerization plays a critical role in a novel dominant negative P2RY12 variant identified in a family with severe bleeding.

Science.gov (United States)

Mundell, S J; Rabbolini, D; Gabrielli, S; Chen, Q; Aungraheeta, R; Hutchinson, J L; Kilo, T; Mackay, J; Ward, C M; Stevenson, W; Morel-Kopp, M-C

2018-01-01

Essentials Three dominant variants for the autosomal recessive bleeding disorder type-8 have been described. To date, there has been no phenotype/genotype correlation explaining their dominant transmission. Proline plays an important role in P2Y12R ligand binding and signaling defects. P2Y12R homodimer formation is critical for the receptor function and signaling. Background Although inherited platelet disorders are still underdiagnosed worldwide, advances in molecular techniques are improving disease diagnosis and patient management. Objective To identify and characterize the mechanism underlying the bleeding phenotype in a Caucasian family with an autosomal dominant P2RY12 variant. Methods Full blood counts, platelet aggregometry, flow cytometry and western blotting were performed before next-generation sequencing (NGS). Detailed molecular analysis of the identified variant of the P2Y12 receptor (P2Y12R) was subsequently performed in mammalian cells overexpressing receptor constructs. Results All three referred individuals had markedly impaired ADP-induced platelet aggregation with primary wave only, despite normal total and surface P2Y12R expression. By NGS, a single P2RY12:c.G794C substitution (p.R265P) was identified in all affected individuals, and this was confirmed by Sanger sequencing. Mammalian cell experiments with the R265P-P2Y12R variant showed normal receptor surface expression versus wild-type (WT) P2Y12R. Agonist-stimulated R265P-P2Y12R function (both signaling and surface receptor loss) was reduced versus WT P2Y12R. Critically, R265P-P2Y12R acted in a dominant negative manner, with agonist-stimulated WT P2Y12R activity being reduced by variant coexpression, suggesting dramatic loss of WT homodimers. Importantly, platelet P2RY12 cDNA cloning and sequencing in two affected individuals also revealed three-fold mutant mRNA overexpression, decreasing even further the likelihood of WT homodimer formation. R265 located within extracellular loop 3 (EL3) is

Monozygotic twins discordant for ROHHAD phenotype.

Science.gov (United States)

Patwari, Pallavi P; Rand, Casey M; Berry-Kravis, Elizabeth M; Ize-Ludlow, Diego; Weese-Mayer, Debra E

2011-09-01

Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) falls within a group of pediatric disorders with both respiratory control and autonomic nervous system dysregulation. Children with ROHHAD typically present after 1.5 years of age with rapid weight gain as the initial sign. Subsequently, they develop alveolar hypoventilation, autonomic nervous system dysregulation, and, if untreated, cardiorespiratory arrest. To our knowledge, this is the first report of discordant presentation of ROHHAD in monozygotic twins. Twin girls, born at term, had concordant growth and development until 8 years of age. From 8 to 12 years of age, the affected twin developed features characteristic of ROHHAD including obesity, alveolar hypoventilation, scoliosis, hypothalamic dysfunction (central diabetes insipidus, hypothyroidism, premature pubarche, and growth hormone deficiency), right paraspinal/thoracic ganglioneuroblastoma, seizures, and autonomic dysregulation including altered pain perception, large and sluggishly reactive pupils, hypothermia, and profound bradycardia that required a cardiac pacemaker. Results of genetic testing for PHOX2B (congenital central hypoventilation syndrome disease-defining gene) mutations were negative. With early recognition and conservative management, the affected twin had excellent neurocognitive outcome that matched that of the unaffected twin. The unaffected twin demonstrated rapid weight gain later in age but not development of signs/symptoms consistent with ROHHAD. This discordant twin pair demonstrates key features of ROHHAD including the importance of early recognition (especially hypoventilation), complexity of signs/symptoms and clinical course, and importance of initiating comprehensive, multispecialty care. These cases confound the hypothesis of a monogenic etiology for ROHHAD and indicate alternative etiologies including autoimmune or epigenetic phenomenon or a combination of genetic

Molecular dynamics simulation of deformation twin in rocksalt vanadium nitride

International Nuclear Information System (INIS)

Fu, Tao; Peng, Xianghe; Zhao, Yinbo; Li, Tengfei; Li, Qibin; Wang, Zhongchang

2016-01-01

We perform molecular dynamics simulation of nano-indentation with a cylindrical indenter to investigate the formation mechanism of deformation twin in vanadium nitride (VN) with a rocksalt structure. We find that the deformation twins occur during the loading stage, and subsequently conduct a systematic analysis of nucleation, propagation and thickening of a deformation twin. We find that the nucleation of a partial dislocation and its propagation to form a stacking fault are premise of deformation twin formation. The sequential nucleation and propagation of partial dislocation on adjacent parallel {111} planes are found to cause the thickening of the deformation twin. Moreover, the deformation twins can exist in VN at room temperature. - Highlights: • MD simulations of indentation are performed to study the deformation twin in VN. • The deformation twins can occur in VN during the loading stage. • The nucleation, propagation and thickening of a deformation twin are analyzed. • The deformation twins can exist in VN at room temperature.

Gene-Environment Interplay in Twin Models

OpenAIRE

Verhulst, Brad; Hatemi, Peter K.

2013-01-01

In this article, we respond to Shultziner’s critique that argues that identical twins are more alike not because of genetic similarity, but because they select into more similar environments and respond to stimuli in comparable ways, and that these effects bias twin model estimates to such an extent that they are invalid. The essay further argues that the theory and methods that undergird twin models, as well as the empirical studies which rely upon them, are unaware of these potential biases...

Familial resemblance in religiousness in a secular society: a twin study.

Science.gov (United States)

Hvidtjørn, Dorte; Petersen, Inge; Hjelmborg, Jacob; Skytthe, Axel; Christensen, Kaare; Hvidt, Niels C

2013-04-01

It is well known that human behavior and individual psychological traits are moderately to substantially heritable. Over the past decade, an increasing number of studies have explored the genetic and environmental influence on religiousness. These studies originate predominantly from countries generally considered more religious than the very secular northern European countries. Comparisons of the results are complicated by diverse definitions of religiousness, but several studies indicate that the influence of the family environment is most predominant in early life, whereas genetic influences increase with age. We performed a population-based twin study of religiousness in a secular society using data from a Web-based survey sent to 6,707 Danish twins born 1970-1989, who were identified in the Danish Twin Registry. We applied Fishman's three conceptual dimensions of religiousness: cognition, practice, and importance. In all polygenic models and biometric analyses, we controlled for gender and age. The study sample comprised 2,237 same sex twins, a response rate of 45%. We found high correlations within both monozygotic and dizygotic twin pairs in most items of religiousness, indicating a large influence from shared environmental factors. Personal religiousness such as praying to God, believing in God, and finding strength and comfort in religion were more influenced by genetic factors than were social forms of religiousness such as church attendance. We found a small tendency for increasing genetic influence with increasing age for some religious items, but not for all.

Conjoined twin piglets with duplicated cranial and caudal axes.

Science.gov (United States)

McManus, C A; Partlow, G D; Fisher, K R

1994-06-01

Twins with doubling of the cranial and caudal poles, yet having a single thorax, are rare. One set of diprosopus, dipygus porcine conjoined twins was studied. In addition to the conjoining anomaly, these twins also exhibited ambiguous internal reproductive features. The twins had two snouts, three eyes, a single thorax, and were duplicated from the umbilicus caudally. Radiography indicated a single vertebral column in the cervical region. The vertebral columns were separate caudally from this point. There was a total of six limbs--one pair of forelimbs and two pairs of hindlimbs. Many medial structures failed to develop in these twins. Medial cranial nerves V-XII were absent or displaced although apparently normal laterally. The medial palates were present but shortened, whereas the medial mandibular rami had folded back on themselves rostrally to form a midline mass between the two chins. Each twin had only one lateral kidney and one lateral testis. Medial scrotal sacs were present but devoid of a testis. There was a midline, "uterine"-like structure which crossed between the twins. However, histological analysis of this structure revealed it to be dysplastic testicular tissue. The relationship between the abnormal reproductive features in these twins and the conjoining is unclear. The anatomy of these twins, in addition to the literature reviewed, illustrates the internal anatomical heterogeneity of grossly similar conjoined twins. A review of the literature also suggests that conjoined twinning may be more common in swine than was previously suspected.

Recurrent twin-twin transfusion syndrome after selective fetoscopic laser photocoagulation: a systematic review of the literature.

LENUS (Irish Health Repository)

Walsh, C A

2012-11-01

Selective fetoscopic laser photocoagulation (SFLP) is now the treatment of choice for twin-twin transfusion syndrome (TTTS). The incidence of recurrent TTTS following SFLP has been inconsistently reported across different studies. We performed a systematic review of TTTS recurrence following SFLP.

Disease-Concordant Twins Empower Genetic Association Studies

DEFF Research Database (Denmark)

Tan, Qihua; Li, Weilong; Vandin, Fabio

2017-01-01

and ordinary healthy samples as controls. We examined the power gain of the twin-based design for various scenarios (i.e., cases from monozygotic and dizygotic twin pairs concordant for a disease) and compared the power with the ordinary case-control design with cases collected from the unrelated patient...... concordant for a disease, should confer increased power in genetic association analysis because of their genetic relatedness. We conducted a computer simulation study to explore the power advantage of the disease-concordant twin design, which uses singletons from disease-concordant twin pairs as cases...... population. Simulation was done by assigning various allele frequencies and allelic relative risks for different mode of genetic inheritance. In general, for achieving a power estimate of 80%, the sample sizes needed for dizygotic and monozygotic twin cases were one half and one fourth of the sample size...

Increased risk of abortion after genetic amniocentesis in twin pregnancies

DEFF Research Database (Denmark)

Palle, C; Andersen, J W; Tabor, A

1983-01-01

Forty-seven twin pregnancies among 3676 patients who had a genetic amniocentesis between 1973 and 1979, are reported. The detection rate of twins at the time of amniocentesis was 62 per cent. Five (17 per cent) of the 29 women with detected twin pregnancy aborted spontaneously, these are compared...... in at least one sac aborted, while 3 of 20 twin pregnancies with one puncture in each sac aborted (15 per cent). One of 18 (6 per cent) twin pregnancies, where only one sac was punctured, because the twin pregnancies were undetected, aborted. Amniocentesis of both sacs in twin pregnancies seems associated...... with an increased risk of spontaneous abortion. The indications for amniocentesis in twin pregnancies should be critically evaluated....

Receiver sensitivity improvement in spectrally-efficient guard-band twin-SSB-OFDM using an optical IQ modulator

Science.gov (United States)

Chen, Ming; Peng, Miao; Zhou, Hui; Zheng, Zhiwei; Tang, Xionggui; Maivan, Lap

2017-12-01

To further improve receiver sensitivity of spectrally-efficient guard-band direct-detection optical orthogonal frequency-division multiplexing (OFDM) with twin single-side-band (SSB) modulation technique, an optical IQ modulator (IQM) is employed to optimize optical carrier-to-signal power ratio (CSPR). The CSPRs for the guard-band twin-SSB-OFDM signal generated by using dual-drive Mach-Zehnder modulator (DD-MZM) and optical IQM are theoretically analyzed and supported by simulations. The optimal CSPR for the two types of guard-band twin-SSB-OFDM are identified. The simulations exhibit that the error vector magnitude (EVM) performance of the IQM-enabled guard-band twin-SSB-OFDM is improved by more than 4-dB compared to that of the twin-SSB-OFDM enabled by DD-MZM after 80-km single-mode fiber (SMF) transmission. In addition, more than 3-dB and 10 dB receiver sensitivity improvements in terms of received optical power (ROP) and optical signal-to-noise ratio (OSNR) are also achieved, respectively.

Characterizing Blood Metabolomics Profiles Associated with Self-Reported Food Intakes in Female Twins.

Directory of Open Access Journals (Sweden)

Tess Pallister

Full Text Available Using dietary biomarkers in nutritional epidemiological studies may better capture exposure and improve the level at which diet-disease associations can be established and explored. Here, we aimed to identify and evaluate reproducibility of novel biomarkers of reported habitual food intake using targeted and non-targeted metabolomic blood profiling in a large twin cohort. Reported intakes of 71 food groups, determined by FFQ, were assessed against 601 fasting blood metabolites in over 3500 adult female twins from the TwinsUK cohort. For each metabolite, linear regression analysis was undertaken in the discovery group (excluding MZ twin pairs discordant [≥1 SD apart] for food group intake with each food group as a predictor adjusting for age, batch effects, BMI, family relatedness and multiple testing (1.17x10-6 = 0.05/[71 food groups x 601 detected metabolites]. Significant results were then replicated (non-targeted: P<0.05; targeted: same direction in the MZ discordant twin group and results from both analyses meta-analyzed. We identified and replicated 180 significant associations with 39 food groups (P<1.17x10-6, overall consisting of 106 different metabolites (74 known and 32 unknown, including 73 novel associations. In particular we identified trans-4-hydroxyproline as a potential marker of red meat intake (0.075[0.009]; P = 1.08x10-17, ergothioneine as a marker of mushroom consumption (0.181[0.019]; P = 5.93x10-22, and three potential markers of fruit consumption (top association: apple and pears: including metabolites derived from gut bacterial transformation of phenolic compounds, 3-phenylpropionate (0.024[0.004]; P = 1.24x10-8 and indolepropionate (0.026[0.004]; P = 2.39x10-9, and threitol (0.033[0.003]; P = 1.69x10-21. With the largest nutritional metabolomics dataset to date, we have identified 73 novel candidate biomarkers of food intake for potential use in nutritional epidemiological studies. We compiled our findings into the

Digital Twins in Health Care: Ethical Implications of an Emerging Engineering Paradigm.

Science.gov (United States)

Bruynseels, Koen; Santoni de Sio, Filippo; van den Hoven, Jeroen

2018-01-01

Personalized medicine uses fine grained information on individual persons, to pinpoint deviations from the normal. 'Digital Twins' in engineering provide a conceptual framework to analyze these emerging data-driven health care practices, as well as their conceptual and ethical implications for therapy, preventative care and human enhancement. Digital Twins stand for a specific engineering paradigm, where individual physical artifacts are paired with digital models that dynamically reflects the status of those artifacts. When applied to persons, Digital Twins are an emerging technology that builds on in silico representations of an individual that dynamically reflect molecular status, physiological status and life style over time. We use Digital Twins as the hypothesis that one would be in the possession of very detailed bio-physical and lifestyle information of a person over time. This perspective redefines the concept of 'normality' or 'health,' as a set of patterns that are regular for a particular individual , against the backdrop of patterns observed in the population. This perspective also will impact what is considered therapy and what is enhancement, as can be illustrated with the cases of the 'asymptomatic ill' and life extension via anti-aging medicine. These changes are the consequence of how meaning is derived, in case measurement data is available. Moral distinctions namely may be based on patterns found in these data and the meanings that are grafted on these patterns. Ethical and societal implications of Digital Twins are explored. Digital Twins imply a data-driven approach to health care. This approach has the potential to deliver significant societal benefits, and can function as a social equalizer, by allowing for effective equalizing enhancement interventions. It can as well though be a driver for inequality, given the fact that a Digital Twin might not be an accessible technology for everyone, and given the fact that patterns identified across a

Analysis of Side-Wall Structure of Grown-in Twin-Type Octahedral Defects in Czochralski Silicon

Science.gov (United States)

Ueki, Takemi; Itsumi, Manabu; Takeda, Tadao

1998-04-01

We analyzed the side-wall structure of grown-in octahedral defects in Czochralski silicon standard wafers for large-scale integrated circuits. There are two types of twin octahedral defects: an overlapping type and an adjacent type. In the twin octahedral defects of the overlapping type, a hole is formed in the connection part. The side-wall layer in the hole part is formed continually and is the same thickness as the side-wall layers of both octahedrons. In the twin octahedral defects of the adjacent type, a partition layer is formed in the connection part. Our electron energy-loss spectroscopy analyses identified that the side-wall layer includes SiO2.

Sonographic monitoring of complications and anomalies in twin gestations

International Nuclear Information System (INIS)

Coleman, B.G.; Grumbach, K.; Arger, P.H.; Mintz, M.C.; Arenson, R.L.; Mennuti, M.T.; Gabbe, S.G.

1986-01-01

One hundred sixty-eight twin gestations were evaluated to assess the role of US in the diagnosis of obstetric complications and anomalies. US revealed the following complications: symptomatic polyhydramnios (eight cases), myomas (seven), placenta previa (three), and abruption (five). Fetal anomalies included twin-twin transfusion syndrome (two), acardiac anomaly (two), chromosomal abnormality (two), anencephaly (one), hydrocephaly (one), and conjoined twins (two). In 26 gestations intrauterine fetal demise or neonatal death involved one or both twins for a total of 42 deaths, constituting a mortality of 12.5%. No maternal deaths occurred. The impact of sonographic monitoring on the obstetric management of twin gestations is emphasized

Genetic variants influencing phenotypic variance heterogeneity.

Science.gov (United States)

Ek, Weronica E; Rask-Andersen, Mathias; Karlsson, Torgny; Enroth, Stefan; Gyllensten, Ulf; Johansson, Åsa

2018-03-01

Most genetic studies identify genetic variants associated with disease risk or with the mean value of a quantitative trait. More rarely, genetic variants associated with variance heterogeneity are considered. In this study, we have identified such variance single-nucleotide polymorphisms (vSNPs) and examined if these represent biological gene × gene or gene × environment interactions or statistical artifacts caused by multiple linked genetic variants influencing the same phenotype. We have performed a genome-wide study, to identify vSNPs associated with variance heterogeneity in DNA methylation levels. Genotype data from over 10 million single-nucleotide polymorphisms (SNPs), and DNA methylation levels at over 430 000 CpG sites, were analyzed in 729 individuals. We identified vSNPs for 7195 CpG sites (P mean DNA methylation levels. We further showed that variance heterogeneity between genotypes mainly represents additional, often rare, SNPs in linkage disequilibrium (LD) with the respective vSNP and for some vSNPs, multiple low frequency variants co-segregating with one of the vSNP alleles. Therefore, our results suggest that variance heterogeneity of DNA methylation mainly represents phenotypic effects by multiple SNPs, rather than biological interactions. Such effects may also be important for interpreting variance heterogeneity of more complex clinical phenotypes.

Effects of six APOA5 variants, identified in patients with severe hypertriglyceridemia, on in vitro lipoprotein lipase activity and receptor binding

NARCIS (Netherlands)

Dorfmeister, B.; Zeng, W. W.; Dichlberger, A.; Nilsson, S. K.; Schaap, F. G.; Hubacek, J. A.; Merkel, M.; Cooper, J. A.; Lookene, A.; Putt, W.; Whittall, R.; Lee, P. J.; Lins, L.; Delsaux, N.; Nierman, M.; Kuivenhoven, J. A.; Kastelein, J. J. P.; Vrablik, M.; Olivecrona, G.; Schneider, W. J.; Heeren, J.; Humphries, S. E.; Talmud, P. J.

2008-01-01

OBJECTIVE: The purpose of this study was to identify rare APOA5 variants in 130 severe hypertriglyceridemic patients by sequencing, and to test their functionality, since no patient recall was possible. METHODS AND RESULTS: We studied the impact in vitro on LPL activity and receptor binding of 3

Twinning in Zircon: Not a High-Pressure Phenomenon

Science.gov (United States)

Jones, G. A.; Moser, D.; Shieh, S. R.; Barker, I.

2017-12-01

Microtwins in zircon are commonly found in shocked terrestrial and extraterrestrial samples and are potentially important for shock history and crater reconstruction. Twinning is easily observed with both the optical microscope and variety of electron beam techniques. Twinning as a deformation mechanism is consistent with the high strain rates generated during impact. No constitutive relationships, or even general limits on the physical conditions required for twinning in zircon are known, however. Present speculation on the critical quantity for twin formation, i.e. 10s of GPa of shock pressure (Moser et al. 2011, Timms et al., 2012), has no basis in the underlying mechanisms of twin nucleation, which are related to the motion of dislocations. This erroneous value is due to conflation of twinning sensu stricto with a phase transformation to reidite. Reidite occurs as twin-like lamellae occupying the {112} planes which are thought to be a mirror plane for twinning. We review the crystallographic theory of twinning in zircon. We then evaulate several theories on the nucleation of twins along with their necessary stresses involved. Our aim is to show that shock microtwins in zircon can be a `low pressure' shock phenomenon. This 'low pressure' hypothesis is supported by natural samples. These zircons are from the lower crust nearly 80 km from the centre of the Vredefort impact structure—the most distal zircon shock microstructures yet found in the lithosphere. Twins are present in 10% of the zircon grains greater than 50 µm in diameter. As an extensive, 'low pressure' phenomenon, twins are an easily recognized and potentially widespread record of Earth's impact history.Moser, D.E., Cupelli, C. L., Barker, I., Flowers, R. M., Mowman, J. R., Wooden, J. and Hart, R. (2011) New zircon shock phenomena and their use for dating and […] analysis of the Vredefort dome, Canadian Journal of Earth Sciences 48(2), 117-139.Timms, N.E., Reddy, S. M., Healy, D., Nemchin, A. A

Risk Factors Influencing Smoking Behavior: A Turkish Twin Study

Science.gov (United States)

Öncel, Sevgi Yurt; Dick, Danielle M.; Maes, Hermine H.; Alıev, Fazil

2015-01-01

Aim In this study, we introduce the first twin study in Turkey, focusing on smoking behavior, and laying the foundation to register all twins born in Turkey for research purposes. Using Turkish twins will contribute to our understanding of health problems in the context of cultural differences. Materials and methods We assessed 309 twin pairs (339 males and 279 females) aged between 15 and 45 years living in the Kırıkkale and Ankara regions of Turkey, and administered a health and lifestyle interview that included questions about smoking status and smoking history. We analyzed the data using descriptive statistics, t-tests, chi-square tests, and bivariate and multivariate clustered logistic regression. In addition, we fit bivariate Structural Equation Models (SEM) to determine contributions of latent genetic and environmental factors to smoking outcomes in this sample. Results One hundred seventy-eight participants (28.8%) were identified as smokers, smoking every day for a month or longer, of whom 79.2% were males and 20.8% were females. Mean values for number of cigarettes per day and the Fagerstrom Test of Nicotine Dependence (FTND; Fagerstrom, 1978) score were higher in males than in females, and age of onset was earlier in males. There was a significant positive correlation between the FTND score and number of cigarettes smoked per day, and a significant negative correlation between both variables and age at onset of smoking. Our study showed that gender, presence of a smoking twin in the family, age, alcohol use, marital status, daily sports activities, and feeling moody all played a significant role in smoking behavior among twins. The twin analysis suggested that 79.5% of the liability to FTND was influenced by genetic factors and 20.5% by unique environment, while familial resemblance for smoking initiation was best explained by common environmental factors. Conclusions Marked differences in the prevalence of smoking behavior in men versus women were

Late language emergence in 24-month-old twins: heritable and increased risk for late language emergence in twins.

Science.gov (United States)

Rice, Mabel L; Zubrick, Stephen R; Taylor, Catherine L; Gayán, Javier; Bontempo, Daniel E

2014-06-01

This study investigated the etiology of late language emergence (LLE) in 24-month-old twins, considering possible twinning, zygosity, gender, and heritability effects for vocabulary and grammar phenotypes. A population-based sample of 473 twin pairs participated. Multilevel modeling estimated means and variances of vocabulary and grammar phenotypes, controlling for familiality. Heritability was estimated with DeFries-Fulker regression and variance components models to determine effects of heritability, shared environment, and nonshared environment. Twins had lower average language scores than norms for single-born children, with lower average performance for monozygotic than dizygotic twins and for boys than girls, although gender and zygosity did not interact. Gender did not predict LLE. Significant heritability was detected for vocabulary (0.26) and grammar phenotypes (0.52 and 0.43 for boys and girls, respectively) in the full sample and in the sample selected for LLE (0.42 and 0.44). LLE and the appearance of Word Combinations were also significantly heritable (0.22-0.23). The findings revealed an increased likelihood of LLE in twin toddlers compared with single-born children that is modulated by zygosity and gender differences. Heritability estimates are consistent with previous research for vocabulary and add further suggestion of heritable differences in early grammar acquisition.

The Spread of Substance Use and Delinquency between Adolescent Twins

Science.gov (United States)

Laursen, Brett; Hartl, Amy C.; Vitaro, Frank; Brendgen, Mara; Dionne, Ginette; Boivin, Michel

2017-01-01

This investigation examines the spread of problem behaviors (substance use and delinquency) between twin siblings. A sample of 628 twins (151 male twin pairs and 163 female twin pairs) drawn from the Quebec Newborn Twin Study completed inventories describing delinquency and substance use at ages 13, 14, and 15. A 3-wave longitudinal actor-partner…

Atopic diseases in twins born after assisted reproduction

DEFF Research Database (Denmark)

Jäderberg, Ida; Thomsen, Simon F; Kyvik, Kirsten Ohm

2012-01-01

Jäderberg I, Thomsen SF, Kyvik KO, Skytthe A, Backer V. Atopic diseases in twins born after assisted reproduction. Paediatric and Perinatal Epidemiology 2012; 26: 140-145. We examined the risk of atopic diseases in twins born after assisted reproduction. Data on atopic diseases and assisted...... reproduction in 9694 twin pairs, 3-20 years of age, from the Danish Twin Registry were collected via multidisciplinary questionnaires. The risk of atopic diseases in twins born after assisted reproduction was compared with the risk in twins born after spontaneous conception using logistic regression...... and variance components analysis. Children born after assisted reproduction did not have a different risk of atopic outcomes (adjusted odds ratios [95% confidence intervals] for asthma: 0.95 [0.85, 1.07], P = 0.403; hay fever: 1.01 [0.86, 1.18], P = 0.918; and atopic dermatitis: 1.02 [0.81, 1.11], P = 0...

Network perturbation by recurrent regulatory variants in cancer.

Directory of Open Access Journals (Sweden)

Kiwon Jang

2017-03-01

Full Text Available Cancer driving genes have been identified as recurrently affected by variants that alter protein-coding sequences. However, a majority of cancer variants arise in noncoding regions, and some of them are thought to play a critical role through transcriptional perturbation. Here we identified putative transcriptional driver genes based on combinatorial variant recurrence in cis-regulatory regions. The identified genes showed high connectivity in the cancer type-specific transcription regulatory network, with high outdegree and many downstream genes, highlighting their causative role during tumorigenesis. In the protein interactome, the identified transcriptional drivers were not as highly connected as coding driver genes but appeared to form a network module centered on the coding drivers. The coding and regulatory variants associated via these interactions between the coding and transcriptional drivers showed exclusive and complementary occurrence patterns across tumor samples. Transcriptional cancer drivers may act through an extensive perturbation of the regulatory network and by altering protein network modules through interactions with coding driver genes.

Indigenous Manufacturing realization of TWIN Source

Science.gov (United States)

Pandey, R.; Bandyopadhyay, M.; Parmar, D.; Yadav, R.; Tyagi, H.; Soni, J.; Shishangiya, H.; Sudhir Kumar, D.; Shah, S.; Bansal, G.; Pandya, K.; Parmar, K.; Vuppugalla, M.; Gahlaut, A.; Chakraborty, A.

2017-04-01

TWIN source is two RF driver based negative ion source that has been planned to bridge the gap between single driver based ROBIN source (currently operational) and eight river based DNB source (to be operated under IN-TF test facility). TWIN source experiments have been planned at IPR keeping the objective of long term domestic fusion programme to gain operational experiences on vacuum immersed multi driver RF based negative ion source. High vacuum compatible components of twin source are designed at IPR keeping an aim on indigenous built in attempt. These components of TWIN source are mainly stainless steel and OFC-Cu. Being high heat flux receiving components, one of the major functional requirements is continuous heat removal via water as cooling medium. Hence for the purpose stainless steel parts are provided with externally milled cooling lines and that shall be covered with a layer of OFC-cu which would be on the receiving side of high heat flux. Manufacturability of twin source components requires joining of these dissimilar materials via process like electrode position, electron beam welding and vacuum brazing. Any of these manufacturing processes shall give a vacuum tight joint having proper joint strength at operating temperature and pressure. Taking the indigenous development effort vacuum brazing (in non-nuclear environment) has been opted for joining of dissimilar materials of twin source being one of the most reliable joining techniques and commercially feasible across the suppliers of country. Manufacturing design improvisation for the components has been done to suit the vacuum brazing process requirement and to ease some of the machining without comprising over the functional and operational requirements. This paper illustrates the details on the indigenous development effort, design improvisation to suits manufacturability, vacuum brazing basics and its procedures for twin source components.

Seasonality in twin birth rates, Denmark, 1936-84.

Science.gov (United States)

Bonnelykke, B; Søgaard, J; Nielsen, J

1987-12-01

A study was made of seasonality in twin birth rate in Denmark between 1977 and 1984. We studied all twin births (N = 45,550) in all deliveries (N = 3,679,932) during that period. Statistical analysis using a simple harmonic sinusoidal model provided no evidence for seasonality. However, sequential polynomial analysis disclosed a significant fit to a fifth order polynomial curve with peaks in twin birth rates in May-June and December, along with troughs in February and September. A falling trend in twinning rate broke off in Denmark around 1970, and from 1970 to 1984 an increasing trend was found. The results are discussed in terms of possible environmental influences on twinning.

Outcome reporting across randomised trials and observational studies evaluating treatments for Twin-Twin Transfusion Syndrome: a systematic review.

Science.gov (United States)

Perry, Helen; Duffy, James M N; Umadia, Ogochukwu; Khalil, Asma

2018-04-01

Twin-Twin Transfusion syndrome is associated with significant mortality and morbidity. Potential treatments require robust evaluation. The aim of this study was to evaluate outcome reporting across observational studies and randomised controlled trials assessing treatments for twin-twin transfusion syndrome (TTTS). Cochrane Central Register of Controlled Trials, EMBASE and Medline were searched from inception to August 2016. Observational studies and randomised controlled trials reporting outcomes following a treatment for TTTS in monochorionic-diamniotic twin pregnancies and monochorionic-triamniotic or dichorionic-triamniotic triplet pregnancies were included. We systematically extracted and categorised outcome reporting. Six randomised trials and 94 observational studies, reporting data from 20,071 maternal participants and 3,199 children, were included. Six different treatments were evaluated. Included studies reported sixty-two different outcomes, including 10 fetal, 28 neonatal, 6 early childhood and 18 maternal outcomes. The outcomes were inconsistently reported across trials. For example, when considering offspring mortality, 31 studies (31%) reported live birth, 31 studies (31%) reported intrauterine death, 49 studies (49%) reported neonatal mortality, and 17 studies (17%) reported perinatal mortality. Four studies (4%) reported respiratory distress syndrome. Only 19 (19%) of studies were designed for long-term follow-up and 11 of these studies (11%) reported cerebral palsy. Most studies evaluating treatments for TTTS, have often neglected to report clinically important outcomes, especially neonatal morbidity outcomes. Most studies are not designed for long-term follow-up. The development of a core outcome set could help standardised outcome collection and reporting in Twin-Twin Transfusion syndrome studies. This article is protected by copyright. All rights reserved.

Confined Blood Chimerism in Monochorionic Dizygotic Twins Conceived Spontaneously

Directory of Open Access Journals (Sweden)

Takashi Kanda

2013-05-01

Full Text Available Traditionally, monochorionicity has been regarded as synonymous with monozygosity. However, several recent cases of monochorionic dizygotic twins have shown that monochorionic twins can be dizygous. We report a rare case of monochorionic diamnionic, gender-discordant twins who were conceived spontaneously. Initially, a monochorionic placenta was diagnosed by ultrasonography at 8 weeks of gestation and then confirmed by pathology after delivery. The twins had different genders. A comparison of cytogenetic analyses using peripheral blood lymphocytes and skin fibroblasts revealed that chimerism was confined to blood cells. We have experienced two cases of monochorionic dizygotic twins since 2003. These cases suggest that monochorionic dizygotic twins are not as rare as previously thought.

Characterizing Blood Metabolomics Profiles Associated with Self-Reported Food Intakes in Female Twins.

Science.gov (United States)

Pallister, Tess; Jennings, Amy; Mohney, Robert P; Yarand, Darioush; Mangino, Massimo; Cassidy, Aedin; MacGregor, Alexander; Spector, Tim D; Menni, Cristina

2016-01-01

Using dietary biomarkers in nutritional epidemiological studies may better capture exposure and improve the level at which diet-disease associations can be established and explored. Here, we aimed to identify and evaluate reproducibility of novel biomarkers of reported habitual food intake using targeted and non-targeted metabolomic blood profiling in a large twin cohort. Reported intakes of 71 food groups, determined by FFQ, were assessed against 601 fasting blood metabolites in over 3500 adult female twins from the TwinsUK cohort. For each metabolite, linear regression analysis was undertaken in the discovery group (excluding MZ twin pairs discordant [≥1 SD apart] for food group intake) with each food group as a predictor adjusting for age, batch effects, BMI, family relatedness and multiple testing (1.17x10-6 = 0.05/[71 food groups x 601 detected metabolites]). Significant results were then replicated (non-targeted: Pfood groups (Pfood intake for potential use in nutritional epidemiological studies. We compiled our findings into the DietMetab database (http://www.twinsuk.ac.uk/dietmetab-data/), an online tool to investigate our top associations.

Does the sex of one's co-twin affect height and BMI in adulthood? A study of dizygotic adult twins from 31 cohorts.

Science.gov (United States)

Bogl, Leonie H; Jelenkovic, Aline; Vuoksimaa, Eero; Ahrenfeldt, Linda; Pietiläinen, Kirsi H; Stazi, Maria A; Fagnani, Corrado; D'Ippolito, Cristina; Hur, Yoon-Mi; Jeong, Hoe-Uk; Silberg, Judy L; Eaves, Lindon J; Maes, Hermine H; Bayasgalan, Gombojav; Narandalai, Danshiitsoodol; Cutler, Tessa L; Kandler, Christian; Jang, Kerry L; Christensen, Kaare; Skytthe, Axel; Kyvik, Kirsten O; Cozen, Wendy; Hwang, Amie E; Mack, Thomas M; Derom, Catherine A; Vlietinck, Robert F; Nelson, Tracy L; Whitfield, Keith E; Corley, Robin P; Huibregtse, Brooke M; McAdams, Tom A; Eley, Thalia C; Gregory, Alice M; Krueger, Robert F; McGue, Matt; Pahlen, Shandell; Willemsen, Gonneke; Bartels, Meike; van Beijsterveldt, Toos C E M; Pang, Zengchang; Tan, Qihua; Zhang, Dongfeng; Martin, Nicholas G; Medland, Sarah E; Montgomery, Grant W; Hjelmborg, Jacob V B; Rebato, Esther; Swan, Gary E; Krasnow, Ruth; Busjahn, Andreas; Lichtenstein, Paul; Öncel, Sevgi Y; Aliev, Fazil; Baker, Laura A; Tuvblad, Catherine; Siribaddana, Sisira H; Hotopf, Matthew; Sumathipala, Athula; Rijsdijk, Fruhling; Magnusson, Patrik K E; Pedersen, Nancy L; Aslan, Anna K Dahl; Ordoñana, Juan R; Sánchez-Romera, Juan F; Colodro-Conde, Lucia; Duncan, Glen E; Buchwald, Dedra; Tarnoki, Adam D; Tarnoki, David L; Yokoyama, Yoshie; Hopper, John L; Loos, Ruth J F; Boomsma, Dorret I; Sørensen, Thorkild I A; Silventoinen, Karri; Kaprio, Jaakko

2017-01-01

The comparison of traits in twins from opposite-sex (OS) and same-sex (SS) dizygotic twin pairs is considered a proxy measure of prenatal hormone exposure. To examine possible prenatal hormonal influences on anthropometric traits, we compared mean height, body mass index (BMI), and the prevalence of being overweight or obese between men and women from OS and SS dizygotic twin pairs. The data were derived from the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) database, and included 68,494 SS and 53,808 OS dizygotic twin individuals above the age of 20 years from 31 twin cohorts representing 19 countries. Zygosity was determined by questionnaires or DNA genotyping depending on the study. Multiple regression and logistic regression models adjusted for cohort, age, and birth year with the twin type as a predictor were carried out to compare height and BMI in twins from OS pairs with those from SS pairs and to calculate the adjusted odds ratios and 95% confidence intervals for being overweight or obese. OS females were, on average, 0.31 cm (95% confidence interval (CI) 0.20, 0.41) taller than SS females. OS males were also, on average, taller than SS males, but this difference was only 0.14 cm (95% CI 0.02, 0.27). Mean BMI and the prevalence of overweight or obesity did not differ between males and females from SS and OS twin pairs. The statistically significant differences between OS and SS twins for height were small and appeared to reflect our large sample size rather than meaningful differences of public health relevance. We found no evidence to support the hypothesis that prenatal hormonal exposure or postnatal socialization (i.e., having grown up with a twin of the opposite sex) has a major impact on height and BMI in adulthood.

Familial aggregation of atrial fibrillation: a study in Danish twins

DEFF Research Database (Denmark)

Christophersen, Ingrid Elisabeth; Ravn, Lasse Steen; Budtz-Joergensen, Esben

2009-01-01

BACKGROUND: Heritability may play a role in nonfamilial atrial fibrillation (AF). We hypothesized that a monozygotic (MZ) twin whose co-twin was diagnosed with AF would have an increased risk of the disease compared with a dizygotic (DZ) twin in the same situation. METHODS AND RESULTS: A sample......-free survival times, we compared the time span between occurrences of disease in MZ and DZ twins. The unaffected twin was included when his or her twin-sibling (the index twin) was diagnosed with AF. After adjustment for age at entry, MZ twins had a significantly shorter event-free survival time (hazard ratio......, 2.0; 95% CI, 1.3 to 3.0), thereby indicating a genetic component. Using biometric models, we estimated the heritability of AF to be 62% (55% to 68%), due to additive genetics. There were no significant differences across sexes. CONCLUSIONS: All the analyses of twin similarities in the present study...

Does anemia-polycythemia complicating twin-twin transfusion syndrome affect outcome after fetoscopic laser surgery?

Science.gov (United States)

Donepudi, R; Papanna, R; Snowise, S; Johnson, A; Bebbington, M; Moise, K J

2016-03-01

Twin anemia-polycythemia sequence (TAPS) can occur as a unique disease or as a complication of twin-twin transfusion syndrome (TTTS). Middle cerebral artery (MCA) Doppler studies are not currently part of the routine evaluation of monochorionic twins since they are not used in the Quintero staging system. As such, the true incidence of TAPS is unknown. We aimed to compare the characteristics and outcomes of twin pregnancies with TTTS complicated by spontaneous anemia-polycythemia vs those with TTTS alone. This was a secondary analysis of data collected prospectively from a cohort of 156 consecutive patients undergoing fetoscopic laser surgery for TTTS, between October 2011 and August 2014. TAPS was defined as discordance in the preoperative MCA peak systolic velocity (PSV), with one twin fetus having MCA-PSV ≤ 1.0 multiples of the median (MoM) and the other having MCA-PSV ≥ 1.5 MoM. Maternal demographics as well as preoperative, operative and postoperative variables were analyzed. Included in the final analysis were 133 patients with complete records: 11 cases with TTTS with anemia-polycythemia and 122 cases with TTTS alone. There was no difference in maternal body mass index, gestational age (GA) at procedure, rate of preterm prelabor rupture of membranes or GA at delivery between the two groups. Patients with TTTS and anemia-polycythemia were more likely to be older (P = 0.03) and parous (P = 0.04) and had a significantly lower number of placental anastomoses (P = 0.01). The dual live-birth rate was similar for both groups (P = 0.76). Cases of TTTS with anemia-polycythemia were more likely to be found in parous and older women and were characterized by fewer vascular anastomoses. TTTS with anemia-polycythemia was not associated with worse perinatal outcome after laser therapy. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Hypothesis test for synchronization: twin surrogates revisited.

Science.gov (United States)

Romano, M Carmen; Thiel, Marco; Kurths, Jürgen; Mergenthaler, Konstantin; Engbert, Ralf

2009-03-01

The method of twin surrogates has been introduced to test for phase synchronization of complex systems in the case of passive experiments. In this paper we derive new analytical expressions for the number of twins depending on the size of the neighborhood, as well as on the length of the trajectory. This allows us to determine the optimal parameters for the generation of twin surrogates. Furthermore, we determine the quality of the twin surrogates with respect to several linear and nonlinear statistics depending on the parameters of the method. In the second part of the paper we perform a hypothesis test for phase synchronization in the case of experimental data from fixational eye movements. These miniature eye movements have been shown to play a central role in neural information processing underlying the perception of static visual scenes. The high number of data sets (21 subjects and 30 trials per person) allows us to compare the generated twin surrogates with the "natural" surrogates that correspond to the different trials. We show that the generated twin surrogates reproduce very well all linear and nonlinear characteristics of the underlying experimental system. The synchronization analysis of fixational eye movements by means of twin surrogates reveals that the synchronization between the left and right eye is significant, indicating that either the centers in the brain stem generating fixational eye movements are closely linked, or, alternatively that there is only one center controlling both eyes.

Investigation of 95 variants identified in a genome-wide study for association with mortality after acute coronary syndrome

Directory of Open Access Journals (Sweden)

Winkelmann Bernhard R

2011-09-01

Full Text Available Abstract Background Genome-wide association studies (GWAS have identified new candidate genes for the occurrence of acute coronary syndrome (ACS, but possible effects of such genes on survival following ACS have yet to be investigated. Methods We examined 95 polymorphisms in 69 distinct gene regions identified in a GWAS for premature myocardial infarction for their association with post-ACS mortality among 811 whites recruited from university-affiliated hospitals in Kansas City, Missouri. We then sought replication of a positive genetic association in a large, racially diverse cohort of myocardial infarction patients (N = 2284 using Kaplan-Meier survival analyses and Cox regression to adjust for relevant covariates. Finally, we investigated the apparent association further in 6086 additional coronary artery disease patients. Results After Cox adjustment for other ACS risk factors, of 95 SNPs tested in 811 whites only the association with the rs6922269 in MTHFD1L was statistically significant, with a 2.6-fold mortality hazard (P = 0.007. The recessive A/A genotype was of borderline significance in an age- and race-adjusted analysis of the entire combined cohort (N = 3095; P = 0.052, but this finding was not confirmed in independent cohorts (N = 6086. Conclusions We found no support for the hypothesis that the GWAS-identified variants in this study substantially alter the probability of post-ACS survival. Large-scale, collaborative, genome-wide studies may be required in order to detect genetic variants that are robustly associated with survival in patients with coronary artery disease.

Prospective risk of fetal death in uncomplicated monochorionic twins.

LENUS (Irish Health Repository)

Farah, Nadine

2012-03-01

A retrospective cohort study was carried out in a university teaching hospital to determine the prospective risk of unexpected fetal death in uncomplicated monochorionic diamniotic (MCDA) twin pregnancies after viability. All MCDA twins delivered at or after 24 weeks\\' gestation from July 1999 to July 2007 were included. Pregnancies with twin-twin transfusion syndrome, growth restriction, structural abnormalities, or twin reversed arterial perfusion sequence were excluded. Of the 144 MCDA twin pregnancies included in our analysis, the risk of intrauterine death was 4.9%. The prospective risk of unexpected intrauterine death was 1 in 43 after 32 weeks\\' gestation and 1 in 37 after 34 weeks\\' gestation. Our results demonstrate that despite close surveillance, the unexpected intrauterine death rate in uncomplicated MCDA twin pregnancies is high. This rate seems to increase after 34 weeks\\' gestation, suggesting that a policy of elective preterm delivery warrants evaluation.

Long-term neurodevelopmental outcome of monochorionic and matched dichorionic twins.

Directory of Open Access Journals (Sweden)

Karien E A Hack

Full Text Available BACKGROUND: Monochorionic (MC twins are at increased risk for perinatal mortality and serious morbidity due to the presence of placental vascular anastomoses. Cerebral injury can be secondary to haemodynamic and hematological disorders during pregnancy (especially twin-to-twin transfusion syndrome (TTTS or intrauterine co-twin death or from postnatal injury associated with prematurity and low birth weight, common complications in twin pregnancies. We investigated neurodevelopmental outcome in MC and dichorionic (DC twins at the age of two years. METHODS: This was a prospective cohort study. Cerebral palsy (CP was studied in 182 MC infants and 189 DC infants matched for weight and age at delivery, gender, ethnicity of the mother and study center. After losses to follow-up, 282 of the 366 infants without CP were available to be tested with the Griffiths Mental Developmental Scales at 22 months corrected age, all born between January 2005 and January 2006 in nine perinatal centers in The Netherlands. Due to phenotypic (unalikeness in mono-or dizygosity, the principal investigator was not blinded to chorionic status; perinatal outcome, with exception of co-twin death, was not known to the examiner. FINDINGS: Four out of 182 MC infants had CP (2.2% - two of the four CP-cases were due to complications specific to MC twin pregnancies (TTTS and co-twin death and the other two cases of CP were the result of cystic PVL after preterm birth - compared to one sibling of a DC twin (0.5%; OR 4.2, 95% CI 0.5-38.2 of unknown origin. Follow-up rate of neurodevelopmental outcome by Griffith's test was 76%. The majority of 2-year-old twins had normal developmental status. There were no significant differences between MC and DC twins. One MC infant (0.7% had a developmental delay compared to 6 DC infants (4.2%; OR 0.2, 95% 0.0-1.4. Birth weight discordancy did not influence long-term outcome, though the smaller twin had slightly lower developmental scores than its

Twin Specific Risk Factors in Primary School Achievements

NARCIS (Netherlands)

de Zeeuw, L.E.J.; van Beijsterveldt, C.E.M.; de Geus, E.J.C.; Boomsma, D.I.

2012-01-01

The main aim of this study was to examine twin specific risk factors that influence educational achievement in primary school. We included prenatal factors that are not unique to twins, except for zygosity, but show a higher prevalence in twins than in singletons. In addition, educational

Cervical column morphology and craniofacial profiles in monozygotic twins.

Science.gov (United States)

Sonnesen, Liselotte; Pallisgaard, Carsten; Kjaer, Inger

2008-02-01

Previous studies have described the relationships between cervical column morphology and craniofacial morphology. The aims of the present study were to describe cervical column morphology in 38 pairs of adult monozygotic (MZ) twins, and compare craniofacial morphology in twins with fusions with craniofacial morphology in twins without fusion. Visual assessment of cervical column morphology and cephalometric measurements of craniofacial morphology were performed on profile radiographs. In the cervical column, fusion between corpora of the second and third vertebrae was registered as fusion. In the twin group, 8 twin pairs had fusion of the cervical column in both individuals within the pair (sub-group A), 25 pairs had no fusions (subgroup B), and in 5 pairs, cervical column morphology was different within the pair (subgroup C), as one twin had fusion and the other did not. Comparison of craniofacial profiles showed a tendency to increased jaw retrognathia, larger cranial base angle, and larger mandibular inclination in subgroup A than in subgroup B. The same tendency was observed within subgroup C between the individual twins with fusion compared with those without fusion. These results confirm that cervical fusions and craniofacial morphology may be interrelated in twins when analysed on profile radiographs. The study also documents that differences in cervical column morphology can occur in individuals within a pair of MZ twins. It illustrates that differences in craniofacial morphology between individuals within a pair of MZ twins can be associated with cervical fusion.

ROTATION PERIODS AND AGES OF SOLAR ANALOGS AND SOLAR TWINS REVEALED BY THE KEPLER MISSION

International Nuclear Information System (INIS)

Do Nascimento Jr, J.-D.; Meibom, S.; García, R. A.; Salabert, D.; Ceillier, T.; Mathur, S.; Anthony, F.; Da Costa, J. S.; Castro, M.; Barnes, S. A.

2014-01-01

A new sample of solar analogs and twin candidates has been constructed and studied, paying particular attention to their light curves from NASA's Kepler mission. This Letter aims to assess their evolutionary status, derive their rotation and ages, and identify those which are solar analogs or solar twin candidates. We separate out the subgiants that compose a large fraction of the asteroseismic sample, and which show an increase in the average rotation period as the stars ascend the subgiant branch. The rotation periods of the dwarfs, ranging from 6 to 30 days and averaging 19 days, allow us to assess their individual evolutionary states on the main sequence and to derive their ages using gyrochronology. These ages are found to be in agreement with a correlation coefficient of r = 0.79 with independent asteroseismic ages, where available. As a result of this investigation, we are able to identify 34 stars as solar analogs and 22 of them as solar twin candidates

ROTATION PERIODS AND AGES OF SOLAR ANALOGS AND SOLAR TWINS REVEALED BY THE KEPLER MISSION

Energy Technology Data Exchange (ETDEWEB)

Do Nascimento Jr, J.-D.; Meibom, S. [Harvard-Smithsonian Center for Astrophysics, Cambridge, MA 02138 (United States); García, R. A.; Salabert, D.; Ceillier, T. [Laboratoire AIM, CEA/DSM,CNRS, Univ. Paris Diderot-IRFU/SAp, Centre de Saclay, F-91191 Gif-sur-Yvette Cedex (France); Mathur, S. [Space Science Institute, 4750 Walnut Street Suite 205, Boulder CO 80301 (United States); Anthony, F.; Da Costa, J. S.; Castro, M. [Universidade Federal do Rio Grande do Norte, UFRN, Dep. de Física Teórica e Experimental, DFTE, CP 1641, 59072-970 Natal, RN (Brazil); Barnes, S. A., E-mail: jdonascimento@cfa.harvard.edu [Leibniz-Institute for Astrophysics, Potsdam D-14467 (Germany)

2014-08-01

A new sample of solar analogs and twin candidates has been constructed and studied, paying particular attention to their light curves from NASA's Kepler mission. This Letter aims to assess their evolutionary status, derive their rotation and ages, and identify those which are solar analogs or solar twin candidates. We separate out the subgiants that compose a large fraction of the asteroseismic sample, and which show an increase in the average rotation period as the stars ascend the subgiant branch. The rotation periods of the dwarfs, ranging from 6 to 30 days and averaging 19 days, allow us to assess their individual evolutionary states on the main sequence and to derive their ages using gyrochronology. These ages are found to be in agreement with a correlation coefficient of r = 0.79 with independent asteroseismic ages, where available. As a result of this investigation, we are able to identify 34 stars as solar analogs and 22 of them as solar twin candidates.

Indentation recovery in GdPO4 and observation of deformation twinning

Directory of Open Access Journals (Sweden)

Taylor M. Wilkinson

2016-09-01

Full Text Available A series of nanoindentation tests on both single and polycrystalline specimens of a monazite rare-earth orthophosphate, GdPO4, revealed frequent observation of anomalous unloading behavior with a large degree of recovery, where previously this behavior had only been observed in xenotime-structure rare-earth orthophosphates. An indentation site in the polycrystalline sample was examined using TEM to identify the deformation mechanism responsible for recovery. The presence of a twin along the (100 orientation, along with a series of stacking faults contained within the deformation site, provide evidence that the mechanism of recovery in GdPO4 is the collapse of deformation twins during unloading.

Juvenile Huntington's disease confirmed by genetic examination in twins Doença de Huntington juvenil confirmada por exame genético em gêmeas

Directory of Open Access Journals (Sweden)

GILBERTO LEVY

1999-09-01

Full Text Available Early-onset Huntington's disease (HD occurs in approximately 10% of HD's cases. We report juvenile HD in phenotypically identical twins, evaluated by history, clinical and neurologic examination, mini-mental state examination, blood laboratory exams, cerebrospinal fluid examination, skull computed tomography, and genetic examination for HD. Patients had the akinetic-rigid variety (Westphal variant of the disease and paternal inheritance. The laboratory workup confirmed the clinical diagnosis of HD, which adds this report to the rare cases of HD in twins reported in the literature.Doença de Huntington (DH de início precoce ocorre em aproximadamente 10% dos casos de DH. Relatamos DH juvenil em gêmeas fenotipicamente idênticas, avaliadas por história, exames clínico e neurológico, mini-exame do estado mental, exames de sangue, exame do líquido cefalorraquidiano, tomografia computadorizada de crânio e exame genético para DH. As pacientes apresentavam a variedade rígido-acinética (variante de Westphal da doença e herança paterna. A avaliação laboratorial confirmou o diagnóstico clínico de DH, acrescentando-se este relato aos raros casos de DH em gêmeos relatados na literatura.

Epidemiological and clinical analysis of a consecutive series of conjoined twins in Spain.

Science.gov (United States)

Martínez-Frías, María Luisa; Bermejo, Eva; Mendioroz, Jacobo; Rodríguez-Pinilla, Elvira; Blanco, Manuel; Egüés, Javier; Félix, Valentín; García, Angel; Huertas, Héctor; Nieto, Carmen; López, José Antonio; López, Santiago; Paisán, Luis; Rosa, Alejandro; Vázquez, María Socorro

2009-04-01

The aim of the study was to analyze the frequency and certain epidemiological characteristics of a consecutive series of conjoined twins born in Spain. We used data from the Spanish Collaborative Study of Congenital Malformations for the period April 1976 to 2006. Because the Spanish law permitting voluntary termination of pregnancies (TOP) when the fetus presented malformations was effective by the end of 1985, we analyzed the data in 4 periods, 2 before 1986 and 2 after. During the first period (1976-1979) only live births were recorded, whereas both still and live births were included in the other three (1980-1985, 1986-1995, and 1996-2006). In the present study, the cases were classified as symmetrical (16 pairs) and asymmetrical (1 pair) conjoined twins. Each pair of conjoined twins was considered as only one case for calculations, regardless of the type of union. Among a total of 2,281,604 consecutive births between 1980 and 2006, there were a total of 15 cases of symmetrical conjoined twins giving a frequency of 0.70 per 100,000 (1/152,107), whereas there was only 1 stillborn asymmetrical conjoined twin pair (0.04/100,000). Among the 13,418 consecutive stillborns surveyed, 6 cases of conjoined twins were identified (either symmetrical or asymmetrical) giving a frequency of 44.72 per 100,000, and 11 pairs were identified among the 2,425,583 total live births surveyed during the first period 1976 to 1979, a frequency of 0.45 per 100,000. Thus, the frequency among stillborn infants is 99.34 times higher than that observed among live births. However, the frequency for the total births (3 last periods) showed a decreasing trend from 1.47 per 100,000 birth in the first period (1980-1985) when TOP was illegal, to a value of 0.09 per 100,000 in the last period, more than 16-fold lower, probably because of the TOP of affected fetuses. Therefore, we consider that the frequencies observed in the period 1980 to 1985 are the basal values in our population. The most

Structures and growth textures of Japanese twin boundaries in quartz

Science.gov (United States)

Momma, K.; Nagase, T.; Kudoh, Y.; Kuribayashi, T.

2008-12-01

Growth textures and atomic configurations of Japanese twin boundaries in quartz were studied by the observation of natural samples and by computational simulations. Samples used in this study are collected from Narushima, Nagasaki Prefecture, Japan. The samples were first polished, and then etched by hydrofluoric acid for several minutes. The etched figures were observed by phase-contrast reflection microscopy and scanning electron microscopy. From these observations, high concentration of Brazil twin lamellae is found near the composition plane of Japanese twin. Observations of cathode luminescence images reveal that the development of Brazil twin lamellae at {112×2} composition plane of Japanese twin is directly related to the preferential growth of Japanese twin along the composition plane. Atomic configurations at {112×2} composition planes of Japanese twin were simulated by using molecular dynamics simulations and the energy minimization method. The simulated structures proved that {112×2} or {1×1×22} composition planes are the only composition planes that do not introduce unsatisfied bonding between Si and O atoms. When the composition plane is different from these planes, some kind of defect structures, like dislocations, are inevitably introduced. In the case of Brazil twin, screw dislocations are also known to be incorporated where orientation of Brazil twin boundary changes from one orientation to another. On the other hand, in the case where Brazil twin boundaries intersect with {112×2} composition planes of Japanese twin, we found that structures are kept coherently without any unsatisfied bonding. This result means that {112×2} composition planes of Japanese twin are the crystallographic sites having more than one possible stacking structures. Observations in this study indicate that {112×2} composition plane of Japanese twin serves as a source of Brazil twin during the course of crystal growth.

Heritability of psoriasis in a large twin sample

DEFF Research Database (Denmark)

Lønnberg, Ann Sophie; Skov, Liselotte; Skytthe, A

2013-01-01

AIM: To study the concordance of psoriasis in a population-based twin sample. METHODS: Data on psoriasis in 10,725 twin pairs, 20-71 years of age, from the Danish Twin Registry was collected via a questionnaire survey. The concordance and heritability of psoriasis were estimated. RESULTS: In total...

Twinning interactions induced amorphisation in ultrafine silicon grains

Energy Technology Data Exchange (ETDEWEB)

Cao, Y. [School of Mechanical and Manufacturing Engineering, University of New South Wales, Sydney, NSW 2052 (Australia); Zhang, L.C., E-mail: liangchi.zhang@unsw.edu.au [School of Mechanical and Manufacturing Engineering, University of New South Wales, Sydney, NSW 2052 (Australia); Zhang, Y. [School of Mechatronics Engineering, Harbin Institute of Technology (China)

2016-03-21

Detailed transmission electron microscopy analysis on a severely deformed Al-Si composite material has revealed that partial dislocation slips and deformation twinning are the major plastic deformation carriers in ultrafine silicon grains. This resembles the deformation twinning activities and mechanisms observed in nano-crystalline face-centred-cubic metallic materials. While deformation twinning and amorphisation in Si were thought unlikely to co-exist, it is observed for the first time that excessive twinning and partial dislocation interactions can lead to localised solid state amorphisation inside ultrafine silicon grains.

Effect of maternal smoking on birth weight of twins: a study from the Dutch Twin Register

NARCIS (Netherlands)

Orlebeke, J.F.; Boomsma, D.I.; van Baal, G.C.M.; Bleker, O.P.

1994-01-01

Since twins weigh about 20% less than singletons at birth, maternal smoking may be a more severe risk for them than for singletons. Therefore, the effect of maternal smoking during pregnancy on birth weight was investigated in a group of 5376 twins. All necessary information was collected by a

Adolescent idiopathic scoliosis in twins: a population-based survey

DEFF Research Database (Denmark)

Andersen, Mikkel O; Thomsen, Karsten; Kyvik, Kirsten O

2007-01-01

STUDY DESIGN: A questionnaire-based identification of adolescent idiopathic scoliosis (AIS) patients in a twin cohort. OBJECTIVE: The purpose of this study was to establish a scoliosis twin cohort to provide data on the heritability of AIS. SUMMARY OF BACKGROUND DATA: The etiology of AIS is still...... environmental factors. METHODS: All 46,418 twins registered in the Danish Twin Registry born from 1931 to 1982 were sent a questionnaire, which included questions about scoliosis. A total of 34,944 (75.3%) representing 23,204 pairs returned the questionnaire. RESULTS: A subgroup of 220 subjects considered...... of monozygotic and dizygotic pairs was significantly different (P scoliosis in 1 twin whose other twin has scoliosis is smaller than believed up until now....

Prevention of preterm delivery in twin pregnancy

DEFF Research Database (Denmark)

Rode, Line; Tabor, Ann

2014-01-01

The incidence of twin gestation has increased markedly over the past decades, mostly because of increased use of assisted reproductive technologies. Twin pregnancies are at increased risk of preterm delivery (i.e. birth before 37 weeks of gestation). Multiple gestations therefore account for 2...... sequelae such as abnormal neurophysiological development in early childhood and underachievement in school. Several treatment modalities have been proposed in singleton high-risk pregnancies. The mechanism of initiating labour may, however, be different in singleton and twin gestations. Therefore......, it is mandatory to evaluate the proposed treatments in randomised trials of multiple gestations. In this chapter, we describe the results of trials to prevent preterm delivery in twin pregnancies....

Ferromagnetic and twin domains in LCMO manganites

International Nuclear Information System (INIS)

Jung, G.; Markovich, V.; Mogilyanski, D.; Beek, C. van der; Mukovskii, Y.M.

2005-01-01

Ferromagnetic and twin domains in lightly Ca-doped La 1-x Ca x MnO 3 single crystals have been visualized and investigated by means of the magneto-optical technique. Both types of domains became visible below the Curie temperature. The dominant structures seen in applied magnetic field are associated with magneto-crystalline anisotropy and twin domains. In a marked difference to the twin domains which appear only in applied magnetic field, ferromagnetic domains show up in zero applied field and are characterized by oppositely oriented spontaneous magnetization in adjacent domains. Ferromagnetic domains take form of almost periodic, corrugated strip-like structures. The corrugation of the ferromagnetic domain pattern is enforced by the underlying twin domains

Bayesian detection of causal rare variants under posterior consistency.

KAUST Repository

Liang, Faming

2013-07-26

Identification of causal rare variants that are associated with complex traits poses a central challenge on genome-wide association studies. However, most current research focuses only on testing the global association whether the rare variants in a given genomic region are collectively associated with the trait. Although some recent work, e.g., the Bayesian risk index method, have tried to address this problem, it is unclear whether the causal rare variants can be consistently identified by them in the small-n-large-P situation. We develop a new Bayesian method, the so-called Bayesian Rare Variant Detector (BRVD), to tackle this problem. The new method simultaneously addresses two issues: (i) (Global association test) Are there any of the variants associated with the disease, and (ii) (Causal variant detection) Which variants, if any, are driving the association. The BRVD ensures the causal rare variants to be consistently identified in the small-n-large-P situation by imposing some appropriate prior distributions on the model and model specific parameters. The numerical results indicate that the BRVD is more powerful for testing the global association than the existing methods, such as the combined multivariate and collapsing test, weighted sum statistic test, RARECOVER, sequence kernel association test, and Bayesian risk index, and also more powerful for identification of causal rare variants than the Bayesian risk index method. The BRVD has also been successfully applied to the Early-Onset Myocardial Infarction (EOMI) Exome Sequence Data. It identified a few causal rare variants that have been verified in the literature.

Bayesian detection of causal rare variants under posterior consistency.

Directory of Open Access Journals (Sweden)

Faming Liang

Full Text Available Identification of causal rare variants that are associated with complex traits poses a central challenge on genome-wide association studies. However, most current research focuses only on testing the global association whether the rare variants in a given genomic region are collectively associated with the trait. Although some recent work, e.g., the Bayesian risk index method, have tried to address this problem, it is unclear whether the causal rare variants can be consistently identified by them in the small-n-large-P situation. We develop a new Bayesian method, the so-called Bayesian Rare Variant Detector (BRVD, to tackle this problem. The new method simultaneously addresses two issues: (i (Global association test Are there any of the variants associated with the disease, and (ii (Causal variant detection Which variants, if any, are driving the association. The BRVD ensures the causal rare variants to be consistently identified in the small-n-large-P situation by imposing some appropriate prior distributions on the model and model specific parameters. The numerical results indicate that the BRVD is more powerful for testing the global association than the existing methods, such as the combined multivariate and collapsing test, weighted sum statistic test, RARECOVER, sequence kernel association test, and Bayesian risk index, and also more powerful for identification of causal rare variants than the Bayesian risk index method. The BRVD has also been successfully applied to the Early-Onset Myocardial Infarction (EOMI Exome Sequence Data. It identified a few causal rare variants that have been verified in the literature.

Bayesian detection of causal rare variants under posterior consistency.

KAUST Repository

Liang, Faming; Xiong, Momiao

2013-01-01

Identification of causal rare variants that are associated with complex traits poses a central challenge on genome-wide association studies. However, most current research focuses only on testing the global association whether the rare variants in a given genomic region are collectively associated with the trait. Although some recent work, e.g., the Bayesian risk index method, have tried to address this problem, it is unclear whether the causal rare variants can be consistently identified by them in the small-n-large-P situation. We develop a new Bayesian method, the so-called Bayesian Rare Variant Detector (BRVD), to tackle this problem. The new method simultaneously addresses two issues: (i) (Global association test) Are there any of the variants associated with the disease, and (ii) (Causal variant detection) Which variants, if any, are driving the association. The BRVD ensures the causal rare variants to be consistently identified in the small-n-large-P situation by imposing some appropriate prior distributions on the model and model specific parameters. The numerical results indicate that the BRVD is more powerful for testing the global association than the existing methods, such as the combined multivariate and collapsing test, weighted sum statistic test, RARECOVER, sequence kernel association test, and Bayesian risk index, and also more powerful for identification of causal rare variants than the Bayesian risk index method. The BRVD has also been successfully applied to the Early-Onset Myocardial Infarction (EOMI) Exome Sequence Data. It identified a few causal rare variants that have been verified in the literature.

The genetic and environmental influences on childhood obesity: a systematic review of twin and adoption studies

DEFF Research Database (Denmark)

Silventoinen, K; Rokholm, B; Kaprio, J

2010-01-01

In this systematic review, we aimed to collect together all previous twin and adoption studies on childhood and adolescent obesity up to the age of 18 years. Using several sources, we identified nine twin and five adoption studies; all of these studies had used relative weight as an indicator...... a substantial effect in mid-childhood, but this effect disappeared at adolescence. Adoption studies supported the role of family environment in childhood obesity as correlations were found between adoptees and adoptive parents; however, correlations were substantially stronger between parents...... of obesity. Except the two twin studies from the Korean population, all studies represented Caucasian populations. In a meta-analysis of these twin studies, we found that genetic factors had a strong effect on the variation of body mass index (BMI) at all ages. The common environmental factors showed...

Conjoined twins: morphogenesis of the heart and a review.

Science.gov (United States)

Gilbert-Barness, Enid; Debich-Spicer, Diane; Opitz, John M

2003-08-01

Five cases of conjoined twins have been studied. These included three thoracopagus twins, one monocephalus diprosopus (prosop = face), and one dicephalus dipus dibrachus. The thoracopagus twins were conjoined only from the upper thorax to the umbilicus with a normal foregut. These three cases shared a single complex multiventricular heart, one with a four chambered heart with one atrium and one ventricle belonging to each twin with complex venous and arterial connection; two had a seven chambered heart with four atria and three ventricles. The mono-cephalus diprosopus twins had a single heart with tetralogy of Fallot. The dicephalus twins had two separate axial skeletons to the sacrum, two separate hearts were connected between the right atria with a shared inferior vena cava. Thoracopagus twinning is associated with complex cardiac malformations. The cardiac anlagen in cephalopagus or diprosopus are diverted and divided along with the entire rostral end of the embryonic disc and result in two relatively normal shared hearts. However, in thoracopagus twins the single heart is multiventricular and suggests very early union with fusion of the cardiac anlagen before significant differentiation. Cardiac morphogenesis in conjoined twins therefore appears to depend on the site of the conjoined fusion and the temporal and spatial influence that determines morphogenesis as well as abnormally oriented embryonic axes. Copyright 2003 Wiley-Liss, Inc.

[Twin pregnancy as the risk factor for neonatal intraventricular hemorrhage].

Science.gov (United States)

Wieczorek, Aleksandra I; Krasomski, Grzegorz

2015-02-01

The aim of this study was to find the perinatal risk factors of intravenricular hemorrhage in twin neonates. A retrospective analysis of 203 twin pregnancies and deliveries between 2003 and 2009 was performed. Then data according birth state and neonatal complications in 406 twins were analyzed. Twin outcome was compared with the outcome of 105 singletons born at the same time and at the same gestational age as twins. Intraventricular hemorrhage was diagnosed in 116/406 (29%) of twins. IVH was found two times more often in the analyzed group than in singletons born at the same gestational age (29% vs. 18%, p = 0,03). In 96% I and II grade hemorrhage was diagnosed and in 4% III and IV grade hemorrhage in the Papille scale was found. 1) Intraventricular hemorrhage is found more often in twins than in singleton neonates born at the same gestational age. 2) IVH in twins correlate with preterm birth and low birth weight. IVH occur more often in twins with birth weight discordance and with too small maternal weight gain.

A population-specific uncommon variant in GRIN3A associated with schizophrenia.

Science.gov (United States)

Takata, Atsushi; Iwayama, Yoshimi; Fukuo, Yasuhisa; Ikeda, Masashi; Okochi, Tomo; Maekawa, Motoko; Toyota, Tomoko; Yamada, Kazuo; Hattori, Eiji; Ohnishi, Tetsuo; Toyoshima, Manabu; Ujike, Hiroshi; Inada, Toshiya; Kunugi, Hiroshi; Ozaki, Norio; Nanko, Shinichiro; Nakamura, Kazuhiko; Mori, Norio; Kanba, Shigenobu; Iwata, Nakao; Kato, Tadafumi; Yoshikawa, Takeo

2013-03-15

Genome-wide association studies have successfully identified several common variants showing robust association with schizophrenia. However, individually, these variants only produce a weak effect. To identify genetic variants with larger effect sizes, increasing attention is now being paid to uncommon and rare variants. From the 1000 Genomes Project data, we selected 47 candidate single nucleotide variants (SNVs), which were: 1) uncommon (minor allele frequency way to discover risk variants with larger effects. Copyright © 2013 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Arterio-venous flow between monochorionic twins determined during intra-uterine transfusion

NARCIS (Netherlands)

van Gemert, Martin J. C.; van den Wijngaard, Jeroen P. H. M.; Lopriore, Enrico; Pasman, Suzanne A.; Vandenbussche, Frank P. H. A.

2008-01-01

Twin-twin transfusion syndrome (TTTS) is a severe complication of monozygotic (identical) twin fetuses sharing one single (monochorionic) placenta. TTTS is caused by a net inter-twin transfusion of blood through placental anastomoses, from one twin (the donor) to the other (the recipient), which

Undiagnosed xiphopagus twins: a perinatal malady

Directory of Open Access Journals (Sweden)

Gowri Dorairajan

2012-02-01

Full Text Available Conjoined twins are a very rare entity. It is associated with poor survival rate in the presence of vital organ sharing. The entity can be diagnosed as early as the first trimester. A conjoined twin diagnosed late in labor is a malady with high perinatal mortality and maternal morbidity. We present one such case of xiphopagus twins. The management of a case diagnosed late in labor can be very challenging. Such obstetric challenges can be avoided by a meticulous early scan with a high index of suspicion, especially in the absence of separating membrane while scanning multiple pregnancies.

Genome-wide placental DNA methylation analysis of severely growth-discordant monochorionic twins reveals novel epigenetic targets for intrauterine growth restriction.

Science.gov (United States)

Roifman, Maian; Choufani, Sanaa; Turinsky, Andrei L; Drewlo, Sascha; Keating, Sarah; Brudno, Michael; Kingdom, John; Weksberg, Rosanna

2016-01-01

Intrauterine growth restriction (IUGR), which refers to reduced fetal growth in the context of placental insufficiency, is etiologically heterogeneous. IUGR is associated not only with perinatal morbidity and mortality but also with adult-onset disorders, such as cardiovascular disease and diabetes, posing a major health burden. Placental epigenetic dysregulation has been proposed as one mechanism that causes IUGR; however, the spectrum of epigenetic pathophysiological mechanisms leading to IUGR remains to be elucidated. Monozygotic monochorionic twins are particularly affected by IUGR, in the setting of severe discordant growth. Because monozygotic twins have the same genotype at conception and a shared maternal environment, they provide an ideal model system for studying epigenetic dysregulation of the placenta. We compared genome-wide placental DNA methylation patterns of severely growth-discordant twins to identify novel candidate genes for IUGR. Snap-frozen placental samples for eight severely growth-discordant monozygotic monochorionic twin pairs were obtained at delivery from each twin. A high-resolution DNA methylation array platform was used to identify methylation differences between IUGR and normal twins. Our analysis revealed differentially methylated regions in the promoters of eight genes: DECR1, ZNF300, DNAJA4, CCL28, LEPR, HSPA1A/L, GSTO1, and GNE. The largest methylation differences between the two groups were in the promoters of DECR1 and ZNF300. The significance of these group differences was independently validated by bisulfite pyrosequencing, implicating aberrations in fatty acid beta oxidation and transcriptional regulation, respectively. Further analysis of the array data identified methylation changes most prominently affecting the Wnt and cadherin pathways in the IUGR cohort. Our results suggest that IUGR in monozygotic twins is associated with impairments in lipid metabolism and transcriptional regulation as well as cadherin and Wnt

Characterization of Gastric Microbiota in Twins.

Science.gov (United States)

Dong, Quanjiang; Xin, Yongning; Wang, Lili; Meng, Xinying; Yu, Xinjuan; Lu, Linlin; Xuan, Shiying

2017-02-01

Contribution of host genetic backgrounds in the development of gastric microbiota has not been clearly defined. This study was aimed to characterize the biodiversity, structure and composition of gastric microbiota among twins. A total of four pairs of twins and eight unrelated individuals were enrolled in the study. Antral biopsies were obtained during endoscopy. The bacterial 16S rRNA gene was amplified and pyrosequenced. Sequences were analyzed for the composition, structure, and α and β diversities of gastric microbiota. Proteobacteria, Firmicutes, Bacteroidetes, Actinobacteria, and Fusobacteria were the most predominant phyla of gastric microbiota. Each individual, twins as well as unrelated individuals, harbored a microbiota of distinct composition. There was no evidence of additional similarity in the richness and evenness of gastric microbiota among co-twins as compared to unrelated individuals. Calculations of θ YC and PCoA demonstrated that the structure similarity of gastric microbial community between co-twins did not increase compared to unrelated individuals. In contrast, the structure of microbiota was altered enormously by Helicobacter pylori infection. These results suggest that host genetic backgrounds had little effect in shaping the gastric microbiota. This property of gastric microbiota could facilitate the studies discerning the role of microbiota from genetic grounds in the pathogenesis.

The morphology of the sella turcica in monozygotic twins

DEFF Research Database (Denmark)

Brock-Jacobsen, Mette T; Pallisgaard, Carsten; Kjaer, Inger

2009-01-01

of 42 twin pairs (18 male and 24 female pairs, aged 18-23 years) comprised the material. Sella turcica measurements from non-twins aged 6-21 years were used as normal reference. Length, depth and diameter of the sella turcica were measured and controlled by re-measurements. Pearson's correlation...... showed that the size of the sella turcica may be partly similar and partly dissimilar within the pair of monozygotic twins. Statistical evaluation of the data showed correlations between length, depth and diameter of the sella turcica between the two twin individuals in the same twin pair. Differences...

Gain-of-function HCN2 variants in genetic epilepsy.

Science.gov (United States)

Li, Melody; Maljevic, Snezana; Phillips, A Marie; Petrovski, Slave; Hildebrand, Michael S; Burgess, Rosemary; Mount, Therese; Zara, Federico; Striano, Pasquale; Schubert, Julian; Thiele, Holger; Nürnberg, Peter; Wong, Michael; Weisenberg, Judith L; Thio, Liu Lin; Lerche, Holger; Scheffer, Ingrid E; Berkovic, Samuel F; Petrou, Steven; Reid, Christopher A

2018-02-01

Genetic generalized epilepsy (GGE) is a common epilepsy syndrome that encompasses seizure disorders characterized by spike-and-wave discharges (SWDs). Pacemaker hyperpolarization-activated cyclic nucleotide-gated channels (HCN) are considered integral to SWD genesis, making them an ideal gene candidate for GGE. We identified HCN2 missense variants from a large cohort of 585 GGE patients, recruited by the Epilepsy Phenome-Genome Project (EPGP), and performed functional analysis using two-electrode voltage clamp recordings from Xenopus oocytes. The p.S632W variant was identified in a patient with idiopathic photosensitive occipital epilepsy and segregated in the family. This variant was also independently identified in an unrelated patient with childhood absence seizures from a European cohort of 238 familial GGE cases. The p.V246M variant was identified in a patient with photo-sensitive GGE and his father diagnosed with juvenile myoclonic epilepsy. Functional studies revealed that both p.S632W and p.V246M had an identical functional impact including a depolarizing shift in the voltage dependence of activation that is consistent with a gain-of-function. In contrast, no biophysical changes resulted from the introduction of common population variants, p.E280K and p.A705T, and the p.R756C variant from EPGP that did not segregate with disease. Our data suggest that HCN2 variants can confer susceptibility to GGE via a gain-of-function mechanism. © 2017 Wiley Periodicals, Inc.

Next generation sequencing identifies abnormal Y chromosome and candidate causal variants in premature ovarian failure patients.

Science.gov (United States)

Lee, Yujung; Kim, Changshin; Park, YoungJoon; Pyun, Jung-A; Kwack, KyuBum

2016-12-01

Premature ovarian failure (POF) is characterized by heterogeneous genetic causes such as chromosomal abnormalities and variants in causal genes. Recently, development of techniques made next generation sequencing (NGS) possible to detect genome wide variants including chromosomal abnormalities. Among 37 Korean POF patients, XY karyotype with distal part deletions of Y chromosome, Yp11.32-31 and Yp12 end part, was observed in two patients through NGS. Six deleterious variants in POF genes were also detected which might explain the pathogenesis of POF with abnormalities in the sex chromosomes. Additionally, the two POF patients had no mutation in SRY but three non-synonymous variants were detected in genes regarding sex reversal. These findings suggest candidate causes of POF and sex reversal and show the propriety of NGS to approach the heterogeneous pathogenesis of POF. Copyright © 2016 Elsevier Inc. All rights reserved.

Comprehensive evaluation of disease- and trait-specific enrichment for eight functional elements among GWAS-identified variants.

Science.gov (United States)

Markunas, Christina A; Johnson, Eric O; Hancock, Dana B

2017-07-01

Genome-wide association study (GWAS)-identified variants are enriched for functional elements. However, we have limited knowledge of how functional enrichment may differ by disease/trait and tissue type. We tested a broad set of eight functional elements for enrichment among GWAS-identified SNPs (p Enrichment analyses were conducted using logistic regression, with Bonferroni correction. Overall, a significant enrichment was observed for all functional elements, except sequence motifs. Missense SNPs showed the strongest magnitude of enrichment. eQTLs were the only functional element significantly enriched across all diseases/traits. Magnitudes of enrichment were generally similar across diseases/traits, where enrichment was statistically significant. Blood vs. brain tissue effects on enrichment were dependent on disease/trait and functional element (e.g., cardiovascular disease: eQTLs P TissueDifference  = 1.28 × 10 -6 vs. enhancers P TissueDifference  = 0.94). Identifying disease/trait-relevant functional elements and tissue types could provide new insight into the underlying biology, by guiding a priori GWAS analyses (e.g., brain enhancer elements for psychiatric disease) or facilitating post hoc interpretation.

Perinatal Mortality Among Twins In Lagos University Teaching ...

African Journals Online (AJOL)

Background: Perinatal mortality rate is reported to be higher in twins than in singletons. More than two decades ago, Abudu and Agarin reported a twinning rate of 21.1/1000 maternities and perinatal mortality rate of 142.6/1000 among twins in Lagos. Objective: To determine the current perinatal mortality rate and risk factors ...

Infantile Perineal Protrusion in Two Monochorionic Twins

Directory of Open Access Journals (Sweden)

Paola Cavicchioli

2014-11-01

Full Text Available Case Report - Two female monochorionic-monoamniotic twins showed the same kind of infantile perineal protrusion (IPP at birth. Lesions in both twins progressively healed until resolution in 6 weeks' time; none of the twins have manifested, till date, alvus disturbances. Discussion and Literature Review - A literature review numbers approximately 100 reports of IPP. This condition has been classically classified into three categories: congenital/familiar (i.e., female sex, positive parental history of IPP, acquired (mainly due to constipation, and associated with lichen sclerosus et atrophicus. Conclusions and Final Remarks - This case report describes, for the first time, the presence of IPP in monochorionic-monoamniotic twins, supporting the existence of hereditary/genetic factors in the developing of this condition.

Decreasing prematurity in twin gestations: predicaments and possibilities.

Science.gov (United States)

Zork, Noelia; Biggio, Joseph; Tita, Alan; Rouse, Dwight; Gyamfi-Bannerman, Cynthia

2013-08-01

The twin birth rate has been steadily increasing in the United States over the past 10 years attributable in large part to the increased use of reproductive technologies. Despite advancements in the prevention of preterm labor for singletons, the overall rate of preterm birth has decreased only minimally. Several interventions to prevent preterm birth in twins have been studied, but none has proven effective. Inpatient bedrest has not been shown to be effective and can cause significant maternal morbidity. Although intramuscular 17α-hydroxyprogesterone caproate is effective in decreasing the risk of recurrent preterm delivery in singletons, neither it nor cerclage is effective in twin gestations, even in those with a short cervix. However, small trials, subgroup analyses, and a meta-analysis suggest that vaginal progesterone and the Arabin cervical pessary may reduce rates of preterm birth in twins of mothers with a short cervix. Given the current lack of effective therapies to prevent preterm birth in twins, large multicenter trials are needed to assess the effectiveness of vaginal progesterone and pessary in twins of mothers with a short cervix.

Emergency separation of a xipho-omphalopagus twin in a developing country

Directory of Open Access Journals (Sweden)

Shukla R

2010-01-01

Full Text Available Female conjoined twins (thoraco-omphalopagus were delivered by emergency caesarean section in a private nursing home. On examination, one of the twins was dead and was threatening the survival of the surviving twin (twin A. An emergency separation was performed to salvage the surviving twin.

Contraction Twinning Dominated Tensile Deformation and Subsequent Fracture in Extruded Mg-1Mn (Wt Pct) at Ambient Temperature

Science.gov (United States)

Chakkedath, A.; Maiti, T.; Bohlen, J.; Yi, S.; Letzig, D.; Eisenlohr, P.; Boehlert, C. J.

2018-03-01

Due to their excellent strength-to-weight ratio, Mg alloys are attractive for applications where weight savings are critical. However, the limited cold formability of wrought Mg alloys severely restricts their widespread usage. In order to study the role that deformation twinning might play in limiting the elongation-to-failure ({ɛ} f ), in-situ tensile tests along the extrusion axis of Mg-1Mn (wt pct) were performed at 323 K, 423 K, and 523 K. The alloy exhibited a strong basal texture such that most of the grains experienced compression along their -axis during deformation. At 323 K, fracture occurred at about 10 pct strain. Although basal, prismatic, and pyramidal slip activity was observed along with extension twinning, contraction twinning significantly influenced the deformation, and such twins evolved into {10{\\bar{1}} 1}-{10{\\bar{1}} 2} double twins. Crystal plasticity simulation showed localized shear deformation within the contraction twins and double twins due to the enhanced activity of basal slip in the reoriented twin volume. Due to this, the twin-matrix interface was identified to be a potential crack initiation site. Thus, contraction twins were considered to have led to the failure of the material at a relatively low strain, suggesting that this deformation mode is detrimental to the cold formability of Mg and its alloys. With increasing temperature, there was a significant decrease in the activity of contraction twinning as well as extension twinning, along with a decrease in the tensile strength and an increase in the {ɛ} f value. A combination of basal, prismatic, and pyramidal slips accounted for a large percentage of the observed deformation activity at 423 K and 523 K. The lack of contraction twinning was explained by the expected decrease in the critical resolved shear stress values for pyramidal slip, and the improved {ɛ} f values at elevated temperatures were attributed to the vanishing activity of contraction twinning.

Contraction Twinning Dominated Tensile Deformation and Subsequent Fracture in Extruded Mg-1Mn (Wt Pct) at Ambient Temperature

Science.gov (United States)

Chakkedath, A.; Maiti, T.; Bohlen, J.; Yi, S.; Letzig, D.; Eisenlohr, P.; Boehlert, C. J.

2018-06-01

Due to their excellent strength-to-weight ratio, Mg alloys are attractive for applications where weight savings are critical. However, the limited cold formability of wrought Mg alloys severely restricts their widespread usage. In order to study the role that deformation twinning might play in limiting the elongation-to-failure ({ɛ} _{ {f}}), in-situ tensile tests along the extrusion axis of Mg-1Mn (wt pct) were performed at 323 K, 423 K, and 523 K. The alloy exhibited a strong basal texture such that most of the grains experienced compression along their -axis during deformation. At 323 K, fracture occurred at about 10 pct strain. Although basal, prismatic, and pyramidal slip activity was observed along with extension twinning, contraction twinning significantly influenced the deformation, and such twins evolved into {10{\\bar{1}}1}-{10{\\bar{1}}2} double twins. Crystal plasticity simulation showed localized shear deformation within the contraction twins and double twins due to the enhanced activity of basal slip in the reoriented twin volume. Due to this, the twin-matrix interface was identified to be a potential crack initiation site. Thus, contraction twins were considered to have led to the failure of the material at a relatively low strain, suggesting that this deformation mode is detrimental to the cold formability of Mg and its alloys. With increasing temperature, there was a significant decrease in the activity of contraction twinning as well as extension twinning, along with a decrease in the tensile strength and an increase in the {ɛ} _{ {f}} value. A combination of basal, prismatic, and pyramidal slips accounted for a large percentage of the observed deformation activity at 423 K and 523 K. The lack of contraction twinning was explained by the expected decrease in the critical resolved shear stress values for pyramidal slip, and the improved {ɛ} _{ {f}} values at elevated temperatures were attributed to the vanishing activity of contraction twinning.

Large-scale gene-centric analysis identifies novel variants for coronary artery disease

NARCIS (Netherlands)

Butterworth, A.S.; Braund, P.S.; Hardwick, R.J.; Saleheen, D.; Peden, J.F.; Soranzo, N.; Chambers, J.C.; Kleber, M.E.; Keating, B.; Qasim, A.; Klopp, N.; Erdmann, J.; Basart, H.; Baumert, J.H.; Bezzina, C.R.; Boehm, B.O.; Brocheton, J.; Bugert, P.; Cambien, F.; Collins, R.; Couper, D.; Jong, J.S. de; Diemert, P.; Ejebe, K.; Elbers, C.C.; Elliott, P.; Fornage, M.; Frossard, P.; Garner, S.; Hunt, S.E.; Kastelein, J.J.; Klungel, O.H.; Kluter, H.; Koch, K.; Konig, I.R.; Kooner, A.S.; Liu, K.; McPherson, R.; Musameh, M.D.; Musani, S.; Papanicolaou, G.; Peters, A.; Peters, B.J.; Potter, S.; Psaty, B.M.; Rasheed, A.; Scott, J.; Seedorf, U.; Sehmi, J.S.; Sotoodehnia, N.; Stark, K.; Stephens, J.; Schoot, C.E. van der; Schouw, Y.T. van der; Harst, P. van der; Vasan, R.S.; Wilde, A.A.; Willenborg, C.; Winkelmann, B.R.; Zaidi, M.; Zhang, W.; Ziegler, A.; Koenig, W.; Matz, W.; Trip, M.D.; Reilly, M.P.; Kathiresan, S.; Schunkert, H.; Hamsten, A.; Hall, A.S.; Kooner, J.S.; Thompson, S.G.; Thompson, J.R.; Watkins, H.; Danesh, J.; Barnes, T.; Rafelt, S.; Codd, V.; Bruinsma, N.; Dekker, L.R.; Henriques, J.P.; Koch, K.T.; Winter, R.J. de; Alings, M.; Allaart, C.F.; Gorgels, A.P.; Verheugt, F.W.A.; Mueller, M.; Meisinger, C.; DerOhannessian, S.; Mehta, N.N.; Ferguson, J.; Hakonarson, H.; Matthai, W.; Wilensky, R.; Hopewell, J.C.; Parish, S.; Linksted, P.; Notman, J.; Gonzalez, H.; Young, A.; Ostley, T.; Munday, A.; Goodwin, N.; Verdon, V.; Shah, S.; Edwards, C.; Mathews, C.; Gunter, R.; Benham, J.; Davies, C.; Cobb, M.; Cobb, L.; Crowther, J.; Richards, A.; Silver, M.; Tochlin, S.; Mozley, S.; Clark, S.; Radley, M.; Kourellias, K.; Olsson, P.; Barlera, S.; Tognoni, G.; Rust, S.; Assmann, G.; Heath, S.; Zelenika, D.; Gut, I.; Green, F.; Farrall, M.; Goel, A.; Ongen, H.; Franzosi, M.G.; Lathrop, M.; Clarke, R.; Aly, A.; Anner, K.; Bjorklund, K.; Blomgren, G.; Cederschiold, B.; Danell-Toverud, K.; Eriksson, P.; Grundstedt, U.; Heinonen, M.; Hellenius, M.L.; Hooft, F. van 't; Husman, K.; Lagercrantz, J.; Larsson, A.; Larsson, M.; Mossfeldt, M.; Malarstig, A.; Olsson, G.; Sabater-Lleal, M.; Sennblad, B.; Silveira, A.; Strawbridge, R.; Soderholm, B.; Ohrvik, J.; Zaman, K.S.; Mallick, N.H.; Azhar, M.; Samad, A.; Ishaq, M.; Shah, N.; Samuel, M.; Kathiresan, S.C.; Assimes, T.L.; Holm, H.; Preuss, M.; Stewart, A.F.; Barbalic, M.; Gieger, C.; Absher, D.; Aherrahrou, Z.; Allayee, H.; Altshuler, D.; Anand, S.; Andersen, K.; Anderson, J.L.; Ardissino, D.; Ball, S.G.; Balmforth, A.J.; Barnes, T.A.; Becker, L.C.; Becker, D.M.; Berger, K.; Bis, J.C.; Boekholdt, S.M.; Boerwinkle, E.; Brown, M.J.; Burnett, M.S.; Buysschaert, I.; Carlquist, J.F.; Chen, L.; Davies, R.W.; Dedoussis, G.; Dehghan, A.; Demissie, S.; Devaney, J.; Do, R.; Doering, A.; El Mokhtari, N.E.; Ellis, S.G.; Elosua, R.; Engert, J.C.; Epstein, S.; Faire, U. de; Fischer, M.; Folsom, A.R.; Freyer, J.; Gigante, B.; Girelli, D.; Gretarsdottir, S.; Gudnason, V.; Gulcher, J.R.; Tennstedt, S.; Halperin, E.; Hammond, N.; Hazen, S.L.; Hofman, A.; Horne, B.D.; Illig, T.; Iribarren, C.; Jones, G.T.; Jukema, J.W.; Kaiser, M.A.; Kaplan, L.M.; Khaw, K.T.; Knowles, J.W.; Kolovou, G.; Kong, A.; Laaksonen, R.; Lambrechts, D.; Leander, K.; Li, M.; Lieb, W.; Lettre, G.; Loley, C.; Lotery, A.J.; Mannucci, P.M.; Martinelli, N.; McKeown, P.P.; Meitinger, T.; Melander, O.; Merlini, P.A.; Mooser, V.; Morgan, T.; Muhleisen T.W., .; Muhlestein, J.B.; Musunuru, K.; Nahrstaedt, J.; Nothen, Markus; Olivieri, O.; Peyvandi, F.; Patel, R.S.; Patterson, C.C.; Qu, L.; Quyyumi, A.A.; Rader, D.J.; Rallidis, L.S.; Rice, C.; Roosendaal, F.R.; Rubin, D.; Salomaa, V.; Sampietro, M.L.; Sandhu, M.S.; Schadt, E.; Schafer, A.; Schillert, A.; Schreiber, S.; Schrezenmeir, J.; Schwartz, S.M.; Siscovick, D.S.; Sivananthan, M.; Sivapalaratnam, S.; Smith, A.V.; Smith, T.B.; Snoep, J.D.; Spertus, J.A.; Stefansson, K.; Stirrups, K.; Stoll, M.; Tang, W.H.; Thorgeirsson, G.; Thorleifsson, G.; Tomaszewski, M.; Uitterlinden, A.G.; Rij, A.M. van; Voight, B.F.; Wareham, N.J.; AWells, G.; Wichmann, H.E.; Witteman, J.C.; Wright, B.J.; Ye, S.; Cupples, L.A.; Quertermous, T.; Marz, W.; Blankenberg, S.; Thorsteinsdottir, U.; Roberts, R.; O'Donnell, C.J.; Onland-Moret, N.C.; Setten, J. van; Bakker, P.I. de; Verschuren, W.M.; Boer, J.M.; Wijmenga, C.; Hofker, M.H.; Maitland-van der Zee, A.H.; Boer, A. de; Grobbee, D.E.; Attwood, T.; Belz, S.; Cooper, J.; Crisp-Hihn, A.; Deloukas, P.; Foad, N.; Goodall, A.H.; Gracey, J.; Gray, E.; Gwilliams, R.; Heimerl, S.; Hengstenberg, C.; Jolley, J.; Krishnan, U.; Lloyd-Jones, H.; Lugauer, I.; Lundmark, P.; Maouche, S.; Moore, J.S.; Muir, D.; Murray, E.; Nelson, C.P.; Neudert, J.; Niblett, D.; O'Leary, K.; Ouwehand, W.H.; Pollard, H.; Rankin, A.; Rice, C.M.; Sager, H.; Samani, N.J.; Sambrook, J.; Schmitz, G.; Scholz, M.; Schroeder, L.; Syvannen, A.C.; Wallace, C.

2011-01-01

Coronary artery disease (CAD) has a significant genetic contribution that is incompletely characterized. To complement genome-wide association (GWA) studies, we conducted a large and systematic candidate gene study of CAD susceptibility, including analysis of many uncommon and functional variants.

Anaesthesia for the separation of conjoined twins

Directory of Open Access Journals (Sweden)

Jaya Lalwani

2011-01-01

Full Text Available Thoraco-omphalopagus is one of the most common type of conjoint twins accounting for 74% cases of conjoint twins. We report the anaesthetic management for successful separation of thoraco-omphalopagus conjoint twins, both of them surviving till date. We highlight the responsibility of anaesthesia team in anaesthetising the two individual patients simultaneously, need of careful monitoring and anticipation of complications like massive blood loss, hypotension, hypokalemia, hypoxia and hypercabia. Detailed description of successful management is reported.

Detwinning mechanisms for growth twins in face-centered cubic metals

Energy Technology Data Exchange (ETDEWEB)

Wang, J., E-mail: wangj6@lanl.gov [Los Alamos National Laboratory, Los Alamos, NM 87545 (United States); Li, N.; Anderoglu, O. [Department of Mechanical Engineering, Materials Science and Engineering Program, Texas A and M University, College Station, TX 77843-3123 (United States); Zhang, X., E-mail: zhangx@tamu.edu [Department of Mechanical Engineering, Materials Science and Engineering Program, Texas A and M University, College Station, TX 77843-3123 (United States); Misra, A. [Los Alamos National Laboratory, Los Alamos, NM 87545 (United States); Huang, J.Y. [Sandia National Laboratories, Albuquerque, NM 87185 (United States); Hirth, J.P. [Los Alamos National Laboratory, Los Alamos, NM 87545 (United States)

2010-04-15

Using in situ transmission electron microscopy, we studied the stability of growth twins. We observed the rapid migration of incoherent twin boundaries (ITBs), indicating that nanotwins are unstable. Topological analysis and atomistic simulations are adopted to explore detwinning mechanisms. The results show that: (i) the detwinning process is accomplished via the collective glide of multiple twinning dislocations that form an ITB; (ii) detwinning can easily occur for thin twins, and the driving force is mainly attributed to a variation of the excess energy of a coherent twin boundary; (iii) shear stresses enable ITBs to migrate easily, causing the motion of coherent twin boundaries; and (iv) the migration velocity depends on stacking fault energy. The results imply that detwinning becomes the dominant deformation mechanism for growth twins of the order of a few nanometers thick.

Relativistic twins or sextuplets?

International Nuclear Information System (INIS)

Sheldon, Eric

2003-01-01

A recent study of the relativistic twin 'paradox' by Soni in this journal affirmed that 'A simple solution of the twin paradox also shows anomalous behaviour of rigidly connected distant clocks' but entailed a pedagogic hurdle which the present treatment aims to surmount. Two scenarios are presented: the first 'flight-plan' is akin to that depicted by Soni, with constant-velocity segments, while the second portrays an alternative mission undertaken with sustained acceleration and deceleration, illustrated quantitatively for a two-way spacecraft flight from Earth to Polaris (465.9 light years distant) and back

Relativistic twins or sextuplets?

CERN Document Server

Sheldon, E S

2003-01-01

A recent study of the relativistic twin 'paradox' by Soni in this journal affirmed that 'A simple solution of the twin paradox also shows anomalous behaviour of rigidly connected distant clocks' but entailed a pedagogic hurdle which the present treatment aims to surmount. Two scenarios are presented: the first 'flight-plan' is akin to that depicted by Soni, with constant-velocity segments, while the second portrays an alternative mission undertaken with sustained acceleration and deceleration, illustrated quantitatively for a two-way spacecraft flight from Earth to Polaris (465.9 light years distant) and back.

Risk of Oral Clefts in Twins

DEFF Research Database (Denmark)

Grosen, Dorthe; Bille, Camilla; Petersen, Inge

2011-01-01

and heritability. Twins (207 affected/130,710) and singletons (7766 affected/4,798,526) born from 1936 through 2004 in Denmark were ascertained by linkage among the Danish Facial Cleft Database, the Danish Twin Registry, and the Civil Registration System. We computed oral cleft prevalence and prevalence proportion...

Association Between Chromosome 9p21 Variants and the Ankle-Brachial Index Identified by a Meta-Analysis of 21 Genome-Wide Association Studies

DEFF Research Database (Denmark)

Murabito, Joanne M; White, Charles C; Kavousi, Maryam

2012-01-01

BACKGROUND: -Genetic determinants of peripheral arterial disease (PAD) remain largely unknown. To identify genetic variants associated with the ankle-brachial index (ABI), a noninvasive measure of PAD, we conducted a meta-analysis of genome-wide association study data from 21 population-based coh...

Association Between Chromosome 9p21 Variants and the Ankle-Brachial Index Identified by a Meta-Analysis of 21 Genome-Wide Association Studies

NARCIS (Netherlands)

Murabito, Joanne M.; White, Charles C.; Kavousi, Maryam; Sun, Yan V.; Feitosa, Mary F.; Nambi, Vijay; Lamina, Claudia; Schillert, Arne; Coassin, Stefan; Bis, Joshua C.; Broer, Linda; Crawford, Dana C.; Franceschini, Nora; Frikke-Schmidt, Ruth; Haun, Margot; Holewijn, Suzanne; Huffman, Jennifer E.; Hwang, Shih-Jen; Kiechl, Stefan; Kollerits, Barbara; Montasser, May E.; Nolte, Ilja M.; Rudock, Megan E.; Senft, Andrea; Teumer, Alexander; van der Harst, Pim; Vitart, Veronique; Waite, Lindsay L.; Wood, Andrew R.; Wassel, Christina L.; Absher, Devin M.; Allison, Matthew A.; Amin, Najaf; Arnold, Alice; Asselbergs, Folkert W.; Aulchenko, Yurii; Bandinelli, Stefania; Barbalic, Maja; Boban, Mladen; Brown-Gentry, Kristin; Couper, David J.; Criqui, Michael H.; Dehghan, Abbas; den Heijer, Martin; Dieplinger, Benjamin; Ding, Jingzhong; Doerr, Marcus; Espinola-Klein, Christine; Felix, Stephan B.; Ferrucci, Luigi; Folsom, Aaron R.; Fraedrich, Gustav; Gibson, Quince; Goodloe, Robert; Gunjaca, Grgo; Haltmayer, Meinhard; Heiss, Gerardo; Hofman, Albert; Kieback, Arne; Kiemeney, Lambertus A.; Kolcic, Ivana; Kullo, Iftikhar J.; Kritchevsky, Stephen B.; Lackner, Karl J.; Li, Xiaohui; Lieb, Wolfgang; Lohman, Kurt; Meisinger, Christa; Melzer, David; Mohler, Emile R.; Mudnic, Ivana; Mueller, Thomas; Navis, Gerjan; Oberhollenzer, Friedrich; Olin, Jeffrey W.; O'Connell, Jeff; O'Donnell, Christopher J.; Palmas, Walter; Penninx, Brenda W.; Petersmann, Astrid; Polasek, Ozren; Psaty, Bruce M.; Rantner, Barbara; Rice, Ken; Rivadeneira, Fernando; Rotter, Jerome I.; Seldenrijk, Adrie; Stadler, Marietta; Summerer, Monika; Tanaka, Toshiko; Tybjaerg-Hansen, Anne; Uitterlinden, Andre G.; van Gilst, Wiek H.; Vermeulen, Sita H.; Wild, Sarah H.; Wild, Philipp S.; Willeit, Johann; Zeller, Tanja; Zemunik, Tatijana; Zgaga, Lina; Assimes, Themistocles L.; Blankenberg, Stefan; Campbell, Harry; Boerwinkle, Eric; Cooke, John P.; de Graaf, Jacqueline; Herrington, David; Kardia, Sharon L. R.; Mitchell, Braxton D.; Murray, Anna; Muenzel, Thomas; Newman, Anne B.; Oostra, Ben A.; Rudan, Igor; Shuldiner, Alan R.; Snieder, Harold; van Duijn, Cornelia M.; Voelker, Uwe; Wright, Alan F.; Wichmann, H. -Erich; Wilson, James F.; Witteman, Jacqueline C. M.; Liu, Yongmei; Hayward, Caroline; Borecki, Ingrid B.; Ziegler, Andreas; North, Kari E.; Cupples, L. Adrienne; Kronenberg, Florian; Dorr, M.; Munzel, T.; Volker, U.

Background-Genetic determinants of peripheral arterial disease (PAD) remain largely unknown. To identify genetic variants associated with the ankle-brachial index (ABI), a noninvasive measure of PAD, we conducted a meta-analysis of genome-wide association study data from 21 population-based cohorts.

[Early prenatal diagnosis of diprosopic syncephalic joined twins].

Science.gov (United States)

Picaud, A; Nlome-Nze, A R; Engongha-Beka, T; Ogowet-Igumu, N

1990-06-01

The authors summarize the case of diprosopic syncephalic joined twins diagnosed at 22 weeks of pregnancy by ultrasonography performed because of hydramnios. The rate of separation anomalies of monozygotic twins is assessed by a review of the literature: from 1 to twenty to fifty thousands for joined twins to 1 per cent fifty thousand to fifteen millions for diprosopus. The etiology is the result of a late division of the egg between D12 and D16. Often an encephalic diprosopic joined twins cause elevated levels of maternal serum alpha protein. Early ultrasonography permits to consider a vaginal therapeutic abortion.

Imperfect twinning: a clinical and ethical dilemma.