Multiple independent genetic factors at NOS1AP modulate the QT interval in a multi-ethnic population.

Extremes of electrocardiographic QT interval are associated with increased risk for sudden cardiac death (SCD); thus, identification and characterization of genetic variants that modulate QT interval may elucidate the underlying etiology of SCD. Previous studies have revealed an association between a common genetic variant in NOS1AP and QT interval in populations of European ancestry, but this finding has not been extended to other ethnic populations. We sought to characterize the effects of NOS1AP genetic variants on QT interval in the multi-ethnic population-based Dallas Heart Study (DHS, n = 3,072). The SNP most strongly associated with QT interval in previous samples of European ancestry, rs16847548, was the most strongly associated in White (P = 0.005) and Black (P = 3.6 x 10(-5)) participants, with the same direction of effect in Hispanics (P = 0.17), and further showed a significant SNP x sex-interaction (P = 0.03). A second SNP, rs16856785, uncorrelated with rs16847548, was also associated with QT interval in Blacks (P = 0.01), with qualitatively similar results in Whites and Hispanics. In a previously genotyped cohort of 14,107 White individuals drawn from the combined Atherosclerotic Risk in Communities (ARIC) and Cardiovascular Health Study (CHS) cohorts, we validated both the second locus at rs16856785 (P = 7.63 x 10(-8)), as well as the sex-interaction with rs16847548 (P = 8.68 x 10(-6)). These data extend the association of genetic variants in NOS1AP with QT interval to a Black population, with similar trends, though not statistically significant at P<0.05, in Hispanics. In addition, we identify a strong sex-interaction and the presence of a second independent site within NOS1AP associated with the QT interval. These results highlight the consistent and complex role of NOS1AP genetic variants in modulating QT interval.

Population amalgamation and genetic variation: observations on artificially agglomerated tribal populations of Central and South America.

The interpretation of data on genetic variation with regard to the relative roles of different evolutionary factors that produce and maintain genetic variation depends critically on our assumptions concerning effective population size and the level of migration between neighboring populations. In humans, recent population growth and movements of specific ethnic groups across wide geographic areas mean that any theory based on assumptions of constant population size and absence of substructure is generally untenable. We examine the effects of population subdivision on the pattern of protein genetic variation in a total sample drawn from an artificial agglomerate of 12 tribal populations of Central and South America, analyzing the pooled sample as though it were a single population. Several striking findings emerge. (1) Mean heterozygosity is not sensitive to agglomeration, but the number of different alleles (allele count) is inflated, relative to neutral mutation/drift/equilibrium expectation. (2) The inflation is most serious for rare alleles, especially those which originally occurred as tribally restricted "private" polymorphisms. (3) The degree of inflation is an increasing function of both the number of populations encompassed by the sample and of the genetic divergence among them. (4) Treating an agglomerated population as though it were a panmictic unit of long standing can lead to serious biases in estimates of mutation rates, selection pressures, and effective population sizes. Current DNA studies indicate the presence of numerous genetic variants in human populations. The findings and conclusions of this paper are all fully applicable to the study of genetic variation at the DNA level as well.

Sociodemographic, behavioral and genetic determinants of allostatic load in a Swiss population-based study.

Allostatic load (AL) is a marker of physiological dysregulation which reflects exposure to chronic stress. High AL has been related to poorer health outcomes including mortality. We examine here the association of socioeconomic and lifestyle factors with AL. Additionally, we investigate the extent to which AL is genetically determined. We included 803 participants (52% women, mean age 48±16years) from a population and family-based Swiss study. We computed an AL index aggregating 14 markers from cardiovascular, metabolic, lipidic, oxidative, hypothalamus-pituitary-adrenal and inflammatory homeostatic axes. Education and occupational position were used as indicators of socioeconomic status. Marital status, stress, alcohol intake, smoking, dietary patterns and physical activity were considered as lifestyle factors. Heritability of AL was estimated by maximum likelihood. Women with a low occupational position had higher AL (low vs. high OR=3.99, 95%CI [1.22;13.05]), while the opposite was observed for men (middle vs. high OR=0.48, 95%CI [0.23;0.99]). Education tended to be inversely associated with AL in both sexes(low vs. high OR=3.54, 95%CI [1.69;7.4]/OR=1.59, 95%CI [0.88;2.90] in women/men). Heavy drinking men as well as women abstaining from alcohol had higher AL than moderate drinkers. Physical activity was protective against AL while high salt intake was related to increased AL risk. The heritability of AL was estimated to be 29.5% ±7.9%. Our results suggest that generalized physiological dysregulation, as measured by AL, is determined by both environmental and genetic factors. The genetic contribution to AL remains modest when compared to the environmental component, which explains approximately 70% of the phenotypic variance.

A genetic record of population isolation in pocket gophers during Holocene climatic change

A long-standing question in Quaternary paleontology is whether climate-induced, population-level phenotypic change is a result of large-scale migration or evolution in isolation. To directly measure genetic variation through time, ancient DNA and morphologic variation was measured over 2,400 years in a Holocene sequence of pocket gophers (Thomomys talpoides) from Lamar Cave, Yellowstone National Park, Wyoming. Ancient specimens and modern samples collected near Lamar Cave share mitochondrial cytochrome b sequences that are absent from adjacent localities, suggesting that the population was isolated for the entire period. In contrast, diastemal length, a morphologic character correlated with body size and nutritional level, changed predictably in response to climatic change. Our results demonstrate that small mammal populations can experience the long-term isolation assumed by many theoretical models of microevolutionary change.

Understanding genetic research and population-based studies /

"P 106"--P. [4] of cover.

Understanding genetic research and population-based studies /

"P 106"--P. [4] of cover.

Genetic diversity and population structure of Tasmanian devils, the largest marsupial carnivore

Genetic diversity and population structure were investigated across the core range of Tasmanian devils (Sarcophilus laniarius; Dasyuridae), a wide-ranging marsupial carnivore restricted to the island of Tasmania. Heterozygosity (0.386-0.467) and allelic diversity (2.7-3.3) were low in all subpopulations and allelic size ranges were small and almost continuous, consistent with a founder effect. Island effects and repeated periods of low population density may also have contributed to the low variation. Within continuous habitat, gene flow appears extensive up to 50 km (high assignment rates to source or close neighbour populations; nonsignificant values of pairwise F-ST), in agreement with movement data. At larger scales (150-250 km), gene flow is reduced (significant pairwise F-ST) but there is no evidence for isolation by distance. The most substantial genetic structuring was observed for comparisons spanning unsuitable habitat, implying limited dispersal of devils between the well-connected, eastern populations and a smaller northwestern population. The genetic distinctiveness of the northwestern population was reflected in all analyses: unique alleles; multivariate analyses of gene frequency (multidimensional scaling, minimum spanning tree, nearest neighbour); high self-assignment (95%); two distinct populations for Tasmania were detected in isolation by distance and in Bayesian model-based clustering analyses. Marsupial carnivores appear to have stronger population subdivisions than their placental counterparts.

An Adaptive Genetic Algorithm with Dynamic Population Size for Optimizing Join Queries

The problem of finding the optimal join ordering executing a query to a relational database management system is a combinatorial optimization problem, which makes deterministic exhaustive solution search unacceptable for queries with a great number of joined relations. In this work an adaptive genetic algorithm with dynamic population size is proposed for optimizing large join queries. The performance of the algorithm is compared with that of several classical non-deterministic optimization algorithms. Experiments have been performed optimizing several random queries against a randomly generated data dictionary. The proposed adaptive genetic algorithm with probabilistic selection operator outperforms in a number of test runs the canonical genetic algorithm with Elitist selection as well as two common random search strategies and proves to be a viable alternative to existing non-deterministic optimization approaches.

Long-finned pilot whale population diversity and structure in Atlantic waters assessed through biogeochemical and genetic markers

Acknowledgements. Cetacean samples were collected under the auspices of stranding monitoring programs run by the Sociedade Portuguesa de Vida Selvagem, the Coordinadora para o Estudio dos Mamíferos Mariños (supported by the regional government Xunta de Galicia), the UK Cetacean Strandings Investigation Programme and the Scottish Agriculture College Veterinary Science Division (jointly funded by Defra and the Devolved Governments of Scotland and Wales), the Marine Mammals Research Group of the Institute of Marine Research (Norway), the Museum of Natural History of the Faroe Islands and the International Fund for Animal Welfare Marine Mammal Rescue and Research Program (USA). The authors thank all the members of these institutions and organizations for their assistance with data and sample collection. S.S.M., P.M.F. and M.F. were supported by PhD grants from the Fundação para a Ciência e Tecnologia (POPH/FSE ref SFRH/BD/ 38735/ 2007, SFRH/BD/36766/2007 and SFRH/BD/30240/ 2006, respectively). A.L. was supported by a postdoctoral grant from the Fundação para a Ciência e Tecnologia (ref SFRH/BPD/82407/2011). The work related to strandings and tissue collection in Portugal was partially supported by the SafeSea project EEAGrants PT 0039 (supported by Iceland, Liechtenstein and Norway through the EEA Financial Mechanism), the MarPro project Life09 NAT/PT/000038 (funded by the European Union program LIFE+) and the project CetSenti FCT RECI/AAG-GLO/0470/2012 (FCOMP- 01-0124-FEDER-027472) (funded by the program COMPETE and the Fundação para a Ciência e Tecnologia). G.J.P. thanks the University of Aveiro and Caixa Geral de Depósitos (Portugal) for financial support. The authors acknowledge the assistance of the chemical analysts at Marine Scotland Science with the fatty acid analysis.

Long-finned pilot whale population diversity and structure in Atlantic waters assessed through biogeochemical and genetic markers

Acknowledgements. Cetacean samples were collected under the auspices of stranding monitoring programs run by the Sociedade Portuguesa de Vida Selvagem, the Coordinadora para o Estudio dos Mamíferos Mariños (supported by the regional government Xunta de Galicia), the UK Cetacean Strandings Investigation Programme and the Scottish Agriculture College Veterinary Science Division (jointly funded by Defra and the Devolved Governments of Scotland and Wales), the Marine Mammals Research Group of the Institute of Marine Research (Norway), the Museum of Natural History of the Faroe Islands and the International Fund for Animal Welfare Marine Mammal Rescue and Research Program (USA). The authors thank all the members of these institutions and organizations for their assistance with data and sample collection. S.S.M., P.M.F. and M.F. were supported by PhD grants from the Fundação para a Ciência e Tecnologia (POPH/FSE ref SFRH/BD/ 38735/ 2007, SFRH/BD/36766/2007 and SFRH/BD/30240/ 2006, respectively). A.L. was supported by a postdoctoral grant from the Fundação para a Ciência e Tecnologia (ref SFRH/BPD/82407/2011). The work related to strandings and tissue collection in Portugal was partially supported by the SafeSea project EEAGrants PT 0039 (supported by Iceland, Liechtenstein and Norway through the EEA Financial Mechanism), the MarPro project Life09 NAT/PT/000038 (funded by the European Union program LIFE+) and the project CetSenti FCT RECI/AAG-GLO/0470/2012 (FCOMP- 01-0124-FEDER-027472) (funded by the program COMPETE and the Fundação para a Ciência e Tecnologia). G.J.P. thanks the University of Aveiro and Caixa Geral de Depósitos (Portugal) for financial support. The authors acknowledge the assistance of the chemical analysts at Marine Scotland Science with the fatty acid analysis.

Heritability and genetic correlations of personality traits in a wild population of yellow-bellied marmots (Marmota flaviventris)

This article is protected by copyright. All rights reserved. Acknowledgments We thank all the marmoteers that helped collect data over the years, and specifically Amanda Lea for help with the pedigree and Leon Chong for help in the field. The comments of two anonymous reviewers helped us improve our original MS. M.B.P. was funded by two U.S. Department of Education GAANN Fellowships, an NSF GK-12 Fellowship, and the UCLA Department of Ecology and Evolutionary Biology. J.G.A.M. was supported by a Marie-Curie Fellowship. D.T.B was supported by the National Geographic Society, UCLA (Faculty Senate and the Division of Life Sciences), a Rocky Mountain Biological Laboratory research fellowship and by the NSF (IDBR-0754247 and DEB-1119660 to D.T.B., as well as DBI 0242960 and 0731346 to the Rocky Mountain Biological Laboratory).