Family-based association analysis with ordered categorical phenotypes, covariates and interactions

Genetic association analyses of family-based studies with ordered categorical phenotypes are often conducted using methods either for quantitative or for binary traits, which can lead to suboptimal analyses. Here we present an alternative likelihood-based method of analysis for single nucleotide polymorphism (SNP) genotypes and ordered categorical phenotypes in nuclear families of any size. Our approach, which extends our previous work for binary phenotypes, permits straightforward inclusion of covariate, gene-gene and gene-covariate interaction terms in the likelihood, incorporates a simple model for ascertainment and allows for family-specific effects in the hypothesis test. Additionally, our method produces interpretable parameter estimates and valid confidence intervals. We assess the proposed method using simulated data, and apply it to a polymorphism in the c-reactive protein (CRP) gene typed in families collected to investigate human systemic lupus erythematosus. By including sex interactions in the analysis, we show that the polymorphism is associated with anti-nuclear autoantibody (ANA) production in females, while there appears to be no effect in males.

Fractal-to-Euclidean crossover of the isotropy restoration feature in a family of fractal resistor networks

Fractal with microscopic anisotropy shows a unique type of macroscopic isotropy restoration phenomenon that is absent in Euclidean space [M. T. Barlow et al., Phys. Rev. Lett. 75, 3042]. In this paper the isotropy restoration feature is considered for a family of two-dimensional Sierpinski gasket type fractal resistor networks. A parameter xi is introduced to describe this phenomenon. Our numerical results show that xi satisfies the scaling law xi similar to l(-alpha), where l is the system size and alpha is an exponent independent of the degree of microscopic anisotropy, characterizing the isotropy restoration feature of the fractal systems. By changing the underlying fractal structure towards the Euclidean triangular lattice through increasing the side length b of the gasket generators, the fractal-to-Euclidean crossover behavior of the isotropy restoration feature is discussed.

The Tnt1 family member Retrosol copy number and structure disclose retrotransposon diversification in different Solanum species

Eukaryotic genome expansion/retraction caused by LTR-retrotransposon activity is dependent on the expression of full length copies to trigger efficient transposition and recombination-driven events. The Tnt1 family of retrotransposons has served as a model to evaluate the diversity among closely related elements within Solanaceae species and found that members of the family vary mainly in their U3 region of the long terminal repeats (LTRs). Recovery of a full length genomic copy of Retrosol was performed through a PCR-based approach from wild potato, Solanum oplocense. Further characterization focusing on both LTR sequences of the amplified copy allowed estimating an approximate insertion time at 2 million years ago thus supporting the occurrence of transposition cycles after genus divergence. Copy number of Tnt1-like elements in Solanum species were determined through genomic quantitative PCR whereby results sustain that Retrosol in Solanum species is a low copy number retrotransposon (1-4 copies) while Retrolyc1 has an intermediate copy number (38 copies) in S. peruvianum. Comparative analysis of retrotransposon content revealed no correlation between genome size or ploidy level and Retrosol copy number. The tetraploid cultivated potato with a cellular genome size of 1,715 Mbp harbours similar copy number per monoploid genome than other diploid Solanum species (613-884 Mbp). Conversely, S. peruvianum genome (1,125 Mbp) has a higher copy number. These results point towards a lineage specific dynamic flux regarding the history of amplification/activity of Tnt1-like elements in the genome of Solanum species.

Vivipary in the cactus family: A reply to Ortega-Baes` et al. evaluation of 25 species from northwestern Argentina

This is a reply to Ortega-Baes` et al. (2010) survey of 25 Argentinean species of cacti evaluated for vivipary. We argue that the sample size and geographic area of the species investigated is insufficient to totally exclude the putative commonness of this condition in the Cactaceae. We indicate possible reasons why they did not find viviparous fruits in their survey. Failure to detect vivipary in cacti of NW Argentina may be correlated with limited taxonomic sampling and geographic region in addition to intrinsic and extrinsic plant factors, including different stages of fruit and seed development and genetic, ecological, and edaphic aspects, which, individually or in concert, control precocious germination. We uphold that viviparity is putatively frequent in this family and list 16 new cases for a total of 53 viviparous cacti, which make up ca. 4% incidence of viviparism in the Cactaceae, a substantially higher percentage than most angiosperm families exhibiting this condition. The Cactaceae ranks fourth in frequency of viviparity after the aquatic families of mangroves and seagrasses. We suggest the re-evaluation of cactus vivipary, primarily as a reproductive adaptation to changing environments and physiological stress with a secondary role as a reproductive strategy with limited offspring dispersal/survival and fitness advantages. (C) 2011 Elsevier Ltd. All rights reserved.

Size and power properties of some tests in the Birnbaum-Saunders regression model

The Birnbaum-Saunders distribution has been used quite effectively to model times to failure for materials subject to fatigue and for modeling lifetime data. In this paper we obtain asymptotic expansions, up to order n(-1/2) and under a sequence of Pitman alternatives, for the non-null distribution functions of the likelihood ratio, Wald, score and gradient test statistics in the Birnbaum-Saunders regression model. The asymptotic distributions of all four statistics are obtained for testing a subset of regression parameters and for testing the shape parameter. Monte Carlo simulation is presented in order to compare the finite-sample performance of these tests. We also present two empirical applications. (C) 2010 Elsevier B.V. All rights reserved.

Asymptotic Skewness in Exponential Family Nonlinear Models

In this article, we give an asymptotic formula of order n(-1/2), where n is the sample size, for the skewness of the distributions of the maximum likelihood estimates of the parameters in exponencial family nonlinear models. We generalize the result by Cordeiro and Cordeiro ( 2001). The formula is given in matrix notation and is very suitable for computer implementation and to obtain closed form expressions for a great variety of models. Some special cases and two applications are discussed.

Skovgaard`s adjustment to likelihood ratio tests in exponential family nonlinear models

Likelihood ratio tests can be substantially size distorted in small- and moderate-sized samples. In this paper, we apply Skovgaard`s [Skovgaard, I.M., 2001. Likelihood asymptotics. Scandinavian journal of Statistics 28, 3-321] adjusted likelihood ratio statistic to exponential family nonlinear models. We show that the adjustment term has a simple compact form that can be easily implemented from standard statistical software. The adjusted statistic is approximately distributed as X(2) with high degree of accuracy. It is applicable in wide generality since it allows both the parameter of interest and the nuisance parameter to be vector-valued. Unlike the modified profile likelihood ratio statistic obtained from Cox and Reid [Cox, D.R., Reid, N., 1987. Parameter orthogonality and approximate conditional inference. journal of the Royal Statistical Society B49, 1-39], the adjusted statistic proposed here does not require an orthogonal parameterization. Numerical comparison of likelihood-based tests of varying dispersion favors the test we propose and a Bartlett-corrected version of the modified profile likelihood ratio test recently obtained by Cysneiros and Ferrari [Cysneiros, A.H.M.A., Ferrari, S.L.P., 2006. An improved likelihood ratio test for varying dispersion in exponential family nonlinear models. Statistics and Probability Letters 76 (3), 255-265]. (C) 2008 Elsevier B.V. All rights reserved.

The family role on the internationalization process of family businesses: a two-case study

Essa dissertação procura identificar o papel da família no processo de internacionalização de dois negócios familiares: JBS, a maior empresa de proteína animal do mundo e Cutrale um dos líderes mundiais no mercado de suco de laranja. Empresas familiares possuem características que são intrínsecas a esse tipo de empresa. Muitos dos motivos de se internacionalizar ou mesmo o modo como eles se internacionalizam podem ser extremamente característicos. Assim, através de uma pesquisa qualitativa, os dois estudos de caso foram analisados baseados em teorias de internacionalização de empresas familiares. Porém, nessas companhias estudadas, a família não desempenhou um papel relevante no processo de internacionalização das mesmas. Com esses resultados, questões surgiram, como por exemplo, se o tamanho ou segmento da empresa tiveram um impacto na importância do papel que a família possui no processo de internacionalização. Essas questões não eram o foco do estudo porém fornecem muitos subsídios para uma próxima pesquisa.

An analysis of the region of the Phocaea dynamical family

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Analysis of plant LTR-retrotransposons at the fine-scale family level reveals individual molecular patterns

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Karyotype characterization of Mugil incilis Hancock, 1830 (Mugiliformes: Mugilidae), including a description of an unusual co-localization of major and minor ribosomal genes in the family

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Cytogenetics studies in Brazilian species of Pseudophyllinae (Orthoptera: Tettigoniidae): 2n(♂)=35 and fn=35 the probable basic and ancestral karyotype of the family tettigoniidae

The karyotypes of five species of Brazilian Pseudophyllinae belonging to four tribes were here studied. The data available in the literature altogether with those obtained with species in here studied allowed us to infer that 2n(♂)=35 is the highest chromosome number found in the family Tettigoniidae and that it is present in species belonging to Pseudophyllinae, Zaprochilinae and in one species of Tettigoniinae. In spite of that all five species exhibit secondary karyotypes arisen surely by a mechanism of chromosomal rearrangement of centric fusion, tandem fusion and centric inversion types from those with 2n(♂)=35 and FN=35, they share some common traits. The X chromosome is submetacentric (FN=36), heteropicnotic during the first prophase, the largest of the set but its size is rather variable among the species and the sex chromosomal mechanism is of the XO( ♂ ), XX( ♀ ) type. The chromosomal rearrangements involved in the karyotype evolution of the Pseudophyllinae and its relationship with those of the family Tettigoniidae are discussed and we propose that the basic and the ancestral karyotype of the Tettigoniidae is formed by 2n(♂)=35, FN=35 and not by 2n(♂)=31, FN= 31, as usually accepted.

Comparative analysis of the testes and spermatogenesis in species of the family Pentatomidae (Heteroptera)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

On the V-type asteroids outside the Vesta family - II. Is (21238) 1995 WV7 a fragment of the long-lost basaltic crust of (15) Eunomia?

Context. The V-type asteroids are associated with basaltic composition. Apart from ( 1459) Magnya, an asteroid that is clearly dynamically and mineralogically unconnected to the Vesta family, all currently known V-type asteroids are either members of the Vesta family, or are hypothesized to be former members of the dynamical family that migrated to their current orbital positions. The recent identification of ( 21238) 1995 WV7 as a V-type asteroid introduces the possibility that a second basaltic asteroid not connected with the Vesta family exists. This asteroid is on the opposite side of the 3: 1 mean motion resonance with respect to Vesta, and it would be very unlikely that a member of the Vesta family of its size (D > 5km) migrating via either the Yarkovsky effect or repeated close encounters with Vesta survived the passage through such a resonance.Aims. In this work we investigate the possibility that ( 21238) 1995 WV7 originated as a fragment of the parent body of the Eunomia family and then migrated via the interplay of the Yarkovsky effect and some powerful nonlinear secular resonances, such as the (s - s(6)) - ( g(5) - g(6)). If (15) Eunomia is, as claimed, a differentiated object whose originally pyroxene-enriched crust layer was lost in a collision that either created the Eunomia family or preceded its formation, can (21238) be a fragment of its long-lost basaltic crust that migrated to the current position?Methods. We mapped the phase space around (21238) and determined which of the nonlinear secular resonances that we identified are stronger and more capable of having caused the current difference in proper i between (21238) and members of the Eunomia family. We simulated the Yarkovsky effect by using the SWIFT-RMVSY integrator.Results. Our results suggest that it is possible to migrate from the Eunomia dynamical family to the current orbital location of ( 21238) via the interplay of the Yarkovsky effect and the (s - s6) - (g5 - g6) nonlinear secular resonance, on time-scales of at least 2.6 Gyr.Conclusions. (15) Eunomia might be the third currently known parent body for V-type asteroids.

Cytogenetic analysis of three sea catfish species (Teleostei, Siluriformes, Ariidae) with the first report of Ag-NOR in this fish family

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)