Complex patterns of male germline instability and somatic mosaicism in myotonic dystrophy type 1

The genetic basis of myotonic dystrophy type 1 (DM1) is the expansion of a CTG repeat in the 3' untranslated region of DM1PK . Once into the disease range, the repeat becomes highly unstable and is biased toward expansion in both somatic and germline tissues. Intergenerational differences usually reveal an increase in allele length, concordant with the clinical anticipation characteristic of DM1, but there have also been cases with intergenerational contractions of the repeat length, accompanied by apparent anticipation. In order to gain a better understanding of this intergenerational behaviour, we have obtained semen samples from six DM males and used single molecule analyses to compare the allele distributions present in their sperm and blood with those of their offspring. We have confirmed that the male germline mutational pathway is distinct from that of the soma, but the extent of variation is highly variable from one individual to another and not obviously correlated with progenitor allele length. Nonetheless, in all cases the alleles present in the father's sperm overlap with those observed in their offspring. These data also provide further indications that the interpretation of intergenerational transmissions by standard analyses is frequently compromised by the masking of germline differences by age-dependent somatic expansion in the parent

Composition and Self-Adaptation of Service-Based Systems with Feature Models

The adoption of mechanisms for reusing software in pervasive systems has not yet become standard practice. This is because the use of pre-existing software requires the selection, composition and adaptation of prefabricated software parts, as well as the management of some complex problems such as guaranteeing high levels of efficiency and safety in critical domains. In addition to the wide variety of services, pervasive systems are composed of many networked heterogeneous devices with embedded software. In this work, we promote the safe reuse of services in service-based systems using two complementary technologies, Service-Oriented Architecture and Software Product Lines. In order to do this, we extend both the service discovery and composition processes defined in the DAMASCo framework, which currently does not deal with the service variability that constitutes pervasive systems. We use feature models to represent the variability and to self-adapt the services during the composition in a safe way taking context changes into consideration. We illustrate our proposal with a case study related to the driving domain of an Intelligent Transportation System, handling the context information of the environment.Work partially supported by the projects TIN2008-05932, TIN2008-01942, TIN2012-35669, TIN2012-34840 and CSD2007-0004 funded by Spanish Ministry of Economy and Competitiveness and FEDER; P09-TIC-05231 and P11-TIC-7659 funded by Andalusian Government; and FP7-317731 funded by EU. Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tec