Genome -wide and locus -specific instability

The discovery of expanded simple repeated sequences causing or associated with human disease has lead to a new area of research involved in the elucidation of how the expanded repeat causes disease and how the repeat becomes unstable. ^ To study the genetic basis of the (CTG)n repeat instability in the DMPK gene in myotonic dystrophy (DM1) patients, somatic cell hybrids were constructed between the lymphocytes of DM1 patients and a variety of Chinese hamster ovary (CHO) cell DNA repair gene deficient mutants. By using small pool PCR (SP-PCR), the instability of the (CTG)n can be quantitated for both the frequency and sizes of length change mutations. ^ Additional SP-PCR analysis on 2/11 subclones generated from this original hybrid showed a marked increase in large repeat deletions, ∼50%. A bimodal distribution of repeats was seen around the progenitor allele and at a large deleted product (within the normal range) with no intermediate products present. ^ To determine if the repair capacity of the CHO cell led to a mutator phenotype in the hamster and hybrid clones, SP-PCR was also done on 3 hamster microsatellites in a variety of hamster cell backgrounds. No variant alleles were seen in over 2500 genome equivalents screened. ^ Human-hamster hybrids have long been shown to be chromosomally unstable, yet information about the stability of repeated sequences was not known. To test if repeat instability was associated with either intact or non-intact human chromosomes, more than 300 microsatellite repeats on 13 human chromosomes (intact and non-intact) were analyzed in eight hybrid cells. No variants were seen between the hybrid and patient alleles in the hybrids. ^ To identify whether DM1 patients have a previously undetected level of genome wide instability or if the instability is truly locus specific, SP-PCR was done on 6 human microsatellites within the patient used to make the hybrid cells. No variants were seen in over 1000 genomes screened. ^ These studies show that the somatic cell hybrid approach is a genetically stable system that allows for the determination of factors that could lead to changes in microsatellite instability. It also shows that there is something inherent about the DM1 expanded (CTG)n repeat that it is solely targeted by, as of yet, and unknown mechanism that causes the repeat to be unstable. (Abstract shortened by UMI.)^

Catamarca, periferia de la periferia : Locus de enunciación y la construcción de contextos de periferia

En este artículo pondremos en tensión la construcción del NOA, Catamarca y específicamente Santa María, a través del tiempo, como ámbitos periféricos desde un punto de vista hegemónico. Desde la perspectiva de la colonialidad del poder, problematizaremos entonces sobre la manera de realizar periodizaciones desde un locus de enunciación que podemos denominar colonialista-capitalista-neoliberal, el que se tornó hegemónico desde la conquista de América. Primero en el período colonial, luego en el desarrollo del capitalismo, y actualmente en el neoliberalismo este locus habilitó una dinámica expropiatoria en el presente vinculada a la mega-minería, que en las últimas dos décadas acentúa la condición de periferia de la región. Esta dinámica entendida como la continuidad de un patrón de poder colonial operó configurando territorios, subjetividades y naturaleza, a lo que agregaremos, la manera de periodizar el tiempo

Catamarca, periferia de la periferia : Locus de enunciación y la construcción de contextos de periferia

En este artículo pondremos en tensión la construcción del NOA, Catamarca y específicamente Santa María, a través del tiempo, como ámbitos periféricos desde un punto de vista hegemónico. Desde la perspectiva de la colonialidad del poder, problematizaremos entonces sobre la manera de realizar periodizaciones desde un locus de enunciación que podemos denominar colonialista-capitalista-neoliberal, el que se tornó hegemónico desde la conquista de América. Primero en el período colonial, luego en el desarrollo del capitalismo, y actualmente en el neoliberalismo este locus habilitó una dinámica expropiatoria en el presente vinculada a la mega-minería, que en las últimas dos décadas acentúa la condición de periferia de la región. Esta dinámica entendida como la continuidad de un patrón de poder colonial operó configurando territorios, subjetividades y naturaleza, a lo que agregaremos, la manera de periodizar el tiempo

Catamarca, periferia de la periferia : Locus de enunciación y la construcción de contextos de periferia

En este artículo pondremos en tensión la construcción del NOA, Catamarca y específicamente Santa María, a través del tiempo, como ámbitos periféricos desde un punto de vista hegemónico. Desde la perspectiva de la colonialidad del poder, problematizaremos entonces sobre la manera de realizar periodizaciones desde un locus de enunciación que podemos denominar colonialista-capitalista-neoliberal, el que se tornó hegemónico desde la conquista de América. Primero en el período colonial, luego en el desarrollo del capitalismo, y actualmente en el neoliberalismo este locus habilitó una dinámica expropiatoria en el presente vinculada a la mega-minería, que en las últimas dos décadas acentúa la condición de periferia de la región. Esta dinámica entendida como la continuidad de un patrón de poder colonial operó configurando territorios, subjetividades y naturaleza, a lo que agregaremos, la manera de periodizar el tiempo

(Table 1) Number of alleles per locus and heterozygosity of Arctic charr (Salvelinus alpinus) populations in Iceland

The ecological theory of adaptive radiation predicts that the evolution of phenotypic diversity within species is generated by divergent natural selection arising from different environments and competition between species. Genetic connectivity among populations is likely also to have an important role in both the origin and maintenance of adaptive genetic diversity. Our goal was to evaluate the potential roles of genetic connectivity and natural selection in the maintenance of adaptive phenotypic differences among morphs of Arctic charr, Salvelinus alpinus, in Iceland. At a large spatial scale, we tested the predictive power of geographic structure and phenotypic variation for patterns of neutral genetic variation among populations throughout Iceland. At a smaller scale, we evaluated the genetic differentiation between two morphs in Lake Thingvallavatn relative to historically explicit, coalescent-based null models of the evolutionary history of these lineages. At the large spatial scale, populations are highly differentiated, but weakly structured, both geographically and with respect to patterns of phenotypic variation. At the intralacustrine scale, we observe modest genetic differentiation between two morphs, but this level of differentiation is nonetheless consistent with strong reproductive isolation throughout the Holocene. Rather than a result of the homogenizing effect of gene flow in a system at migration-drift equilibrium, the modest level of genetic differentiation could equally be a result of slow neutral divergence by drift in large populations. We conclude that contemporary and recent patterns of restricted gene flow have been highly conducive to the evolution and maintenance of adaptive genetic variation in Icelandic Arctic charr.

Failure locus of polypropylene nonwoven fabrics under in-plane biaxial deformation

The failure locus, the characteristics of the stress–strain curve and the damage localization patterns were analyzed in a polypropylene nonwoven fabric under in-plane biaxial deformation. The analysis was carried out by means of a homogenization model developed within the context of the finite element method. It provides the constitutive response for a mesodomain of the fabric corresponding to the area associated to a finite element and takes into account the main deformation and damage mechanisms experimentally observed. It was found that the failure locus in the stress space was accurately predicted by the Von Mises criterion and failure took place by the localization of damage into a crack perpendicular to the main loading axis.

Damage localization and failure locus under biaxial loading in glass-fiber nonwoven felts

The pattern of damage localization and fracture under uniaxial and biaxial tension was studied in glass–fiber nonwoven felts. The analyses were carried out within the framework of the finite-element simulation of plain and notched specimens in which the microstructure of the felt, made up of fiber bundles connected at the cross point through an organic binder, was explicitly represented. Following previous experimental observations, fracture by interbundle decohesion and energy dissipation by frictional sliding between the bundles were included in the model. It was found that the failure path in these materials was controlled by the maximum applied normal stress, regardless of the loading path, and that the failure locus under biaxial tension was well represented by the von Mises failure criteria. The notch sensitivity of the nonwoven felts was limited and the presence of a notch did not modify the failure path.

Variance and covariance of actual relationship between relatives at one locus.

The relationship between pairs of individuals is an important topic in many areas of population and quantitative genetics. It is usually measured as the proportion of thegenome identical by descent shared by the pair and it can be inferred from pedigree information. But there is a variance in actual relationships as a consequence of Mendelian sampling, whose general formula has not been developed. The goal of this work is to develop this general formula for the one-locus situation,. We provide simple expressions for the variances and covariances of all actual relationships in an arbitrary complex pedigree. The proposed method relies on the use of the nine identity coefficients and the generalized relationship coefficients; formulas have been checked by computer simulation. Finally two examples for a short pedigree of dogs and a long pedigree of sheep are given.