A Large Set of Finnish Affected Sibling Pair Families With Type 2 Diabetes Suggests Susceptibility Loci on Chromosomes 6,
11, and 14
Kaisa Silander 1 ,
Laura J. Scott 2 ,
Timo T. Valle 3 ,
Karen L. ...Mohlke 1 ,
Heather M. Stringham 2 ,
Kerry R. Wiles 1 ,
William L. Duren 2 ,
Kimberly F. Doheny 4 ,
Elizabeth W. Pugh 4 ,
Peter Chines 1 ,
Narisu Narisu 1 ,
Peggy P. White 2 ,
Tasha E. Fingerlin 2 ,
Anne U. Jackson 2 ,
Chun Li 2 ,
Soumitra Ghosh 1 ,
Victoria L. Magnuson 1 ,
Kimberly Colby 1 ,
Michael R. Erdos 1 ,
Jason E. Hill 1 ,
Pablo Hollstein 1 ,
Kathleen M. Humphreys 1 ,
Roshni A. Kasad 1 ,
Jessica Lambert 1 ,
Konstantinos N. Lazaridis 1 ,
George Lin 1 ,
Anabelle Morales-Mena 1 ,
Kristin Patzkowski 1 ,
Carrie Pfahl 1 ,
Rachel Porter 1 ,
David Rha 1 ,
Leonid Segal 1 ,
Yong D. Suh 1 ,
Jason Tovar 1 ,
Arun Unni 1 ,
Christian Welch 1 ,
Julie A. Douglas 2 ,
Michael P. Epstein 2 ,
Elizabeth R. Hauser 2 ,
William Hagopian 5 ,
Thomas A. Buchanan 6 ,
Richard M. Watanabe 2 7 ,
Richard N. Bergman 8 ,
Jaakko Tuomilehto 3 9 ,
Francis S. Collins 1 and
Michael Boehnke 2
1 Genome Technology Branch, National Human Genome Research Institute, Bethesda, Maryland
2 Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, Michigan
3 Diabetes and Genetic Epidemiology Unit, Department of Epidemiology and Health Promotion, and Department of Biochemistry, National
Public Health Institute, Helsinki, Finland
4 Center for Inherited Disease Research, Institute of Genetic Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland
5 Pacific Northwest Research Institute, Seattle, Washington
6 Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California
7 Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California
8 Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, California
9 Department of Public Health, University of Helsinki, Helsinki, Finland
Address correspondence and reprint requests to Michael Boehnke, PhD, Department of Biostatistics, School of Public Health,
University of Michigan, 1420 Washington Heights, Ann Arbor, Michigan 48109-2029. E-mail: boehnke{at}umich.edu
Abstract
The aim of the Finland-United States Investigation of NIDDM Genetics (FUSION) study is to identify genes that predispose to
type 2 diabetes or are responsible for variability in diabetes-related traits via a positional cloning and positional candidate
gene approach. In a previously published genome-wide scan of 478 Finnish affected sibling pair (ASP) families (FUSION 1),
the strongest linkage results were on chromosomes 20 and 11. We now report a second genome-wide scan using an independent
set of 242 Finnish ASP families (FUSION 2), a detailed analysis of the combined set of 737 FUSION 1 + 2 families (495 updated
FUSION 1 families), and fine mapping of the regions of chromosomes 11 and 20. The strongest FUSION 2 linkage results were
on chromosomes 6 (maximum logarithm of odds score MLS = 2.30 at 95 cM) and 14 (MLS = 1.80 at 57 cM). For the combined FUSION
1 + 2 families, three results were particularly notable: chromosome 11 (MLS = 2.98 at 82 cM), chromosome 14 (MLS = 2.74 at
58 cM), and chromosome 6 (MLS = 2.66 at 96 cM). We obtained smaller FUSION 1 + 2 MLSs on chromosomes X (MLS = 1.27 at 152
cM) and 20p (MLS = 1.21 at 20 cM). Among the 10 regions that showed nominally significant evidence for linkage in FUSION 1,
four (on chromosomes 6, 11, 14, and X) also showed evidence for linkage in FUSION 2 and stronger evidence for linkage in the
combined FUSION 1 + 2 sample.
ASP, affected sibling pair
CEPH, Centre d’Etude du Polymorphisme Humain
CIDR, Center for Inherited Disease Research
FUSION, Finland-United States Investigation of NIDDM Genetics
IBD, identity by descent
LOD, logarithm of odds
MLS, maximum LOD score
QTL, quantitative trait locus
WHO, World Health Organization
Footnotes
Accepted December 4, 2003.
Received July 21, 2003.
DIABETES
Un proyecto de este tipo se comenzó en el central Jesús Rabí de la provincia de matanzas en el mismo se ha cumplido las expectativas en el desarrollo cañero logrando altos rendimientos asegurando una ...molida por más de 159 días de zafra introduciendo nuevas tecnologías de riego, maquinaria agrícola y cosecha. En la industria solo se lograron avances en la automatización y mejoras tecnológicas en algunas áreas no culminando el proyecto que inicialmente fue diseñado. Conocida esta experiencia AZCUBA se propone implementar en Antonio Sánchez un proyecto de central de nuevo tipo que considere todos los aspectos Agroindustriales y del entorno de la industria. En este trabajo se presenta un diseño de un central de nuevo tipo ajustado a las condiciones de Antonio Sánchez y su entorno, que posibilite las bases para la implementación de la innovación tecnológica en todos los procesos, utilizando procedimientos que aseguren su efectividad y sostenibilidad. Se realizó vigilancia tecnológica en lo referente al estado del arte en las nuevas proyecciones de centrales azucareros modernos, con énfasis en la sostenibilidad económica, ambiental y social. Se proponen alternativas de desarrollo del central, proyectando y adaptando las condiciones de su entorno.
Three-dimensional models of the alpha- and beta-1 subunits of the calcium-activated potassium channel (BK) were predicted by threading modeling. A recursive approach comprising of sequence alignment ...and model building based on three templates was used to build these models, with the refinement of non-conserved regions carried out using threading techniques. The complex formed by the subunits was studied by means of docking techniques, using 3D models of the two subunits, and an approach based on rigid-body structures. Structural effects of the complex were analyzed with respect to hydrogen-bond interactions and binding-energy calculations. Potential interaction sites of the complex were determined by referencing a study of the difference accessible surface area (DASA) of the protein subunits in the complex.
To assess whether the month of birth in different latitudes of South America might influence the presence or severity of multiple sclerosis (MS) later in life.
Neurologists in four South American ...countries working at MS units collected data on their patients' month of birth, gender, age, and disease progression.
Analysis of data from 1207 MS patients and 1207 control subjects did not show any significant variation in the month of birth regarding the prevalence of MS in four latitude bands (0-10; 11-20; 21-30; and 31-40 degrees). There was no relationship between the month of birth and the severity of disease in each latitude band.
The results from this study show that MS patients born to mothers who were pregnant at different Southern latitudes do not follow the seasonal pattern observed at high Northern latitudes.
Elected prosecutors in the US representing more than 17 million people across the country issued a joint statement recommending immediate actions to mitigate community spread of COVID-19 amongst the ...2.3 million adults and children held in prisons, local jails, youth correctional facilities, immigration detention centers, and other forms of confinement. Key recommendations include adopting cite and release policies for any offense that poses no physical threat to the community.
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Introduction
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General features of GRKs
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Expression patterns of GRK2
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GRK, ET‐1 and Insulin signalling
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GRK studies In AD and CBH
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Conclusions
Alzheimer disease (AD) and stroke are two ...leading causes of age‐associated dementia. Increasing evidence points to vascular damage as an early contributor to the development of AD and AD‐like pathology. In this review, we discuss the role of G protein‐coupled receptor kinase 2 (GRK2) as it relates to individuals affected by AD and how the cardiovasculature plays a role in AD pathogenesis. The possible involvement of GRKs in AD pathogenesis is an interesting notion, which may help bridge the gap in our understanding of the heart–brain connection in relation to neurovisceral damage and vascular complications in AD, since kinases of this family are known to regulate numerous receptor functions both in the brain, myocardium, and elsewhere. The aim of this review is to discuss our findings of overexpression of GRK2 in the context of the early pathogenesis of AD, because increased levels of GRK2 immunoreactivity were found in vulnerable neurons of AD patients as well as in a two‐vessel occlusion (2‐VO) mammalian model of ischaemia. Also, we consider the consequences for this overexpression as a loss of G‐protein coupled receptor (GPCR) regulation, as well as suggest a potential role for GPCRs and GRKs in a unifying theory of AD pathogenesis, particularly in the context of cerebrovascular disease. We synthesize this newer information and attempt to put it into context with GRKs as regulators of diverse physiological cellular functions that could be appropriate targets for future pharmacological intervention.
Using the full data set of the NA48/2 experiment, the decay K±→π±e+e−γ is observed for the first time, selecting 120 candidates with 7.3±1.7 estimated background events. With K±→π±πD0 as ...normalisation channel, the branching ratio is determined in a model-independent way to be Br(K±→π±e+e−γ,meeγ>260 MeV/c2)=(1.19±0.12stat±0.04syst)×10−8. This measured value and the spectrum of the e+e−γ invariant mass allow a comparison with predictions of chiral perturbation theory.
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