Type 1 Diabetes in the BB Rat: A Polygenic Disease

OBJECTIVE-Two type 1 diabetes susceptibility genes have been identified in the spontaneously diabetic biobreeding diabetes-prone (BBDP) rat, the major histocompatibility complex (MHC) (RT1) class II u haplotype (Iddm1) and Gimap5 (Iddm2). The strong effects of these have impeded previous efforts to map additional loci. We tested the hypothesis that type 1 diabetes is a polygenic disease in the BBDP rat. RESEARCH DESIGN AND METHODS-We performed the most comprehensive genome-wide linkage analysis for type 1 diabetes, age of disease onset (AOO), and insulitis subpheno- types in 574 F2 animals from a cross-intercross between BBDP and type 1 diabetes-resistant, double congenic ACI.BBDP- RT1u,Gimap5 (ACI.BB 1ulyp) rats, where both Iddm1 and Iddm2 were fixed as BBDP. RESULTS-A total of 19% of these F2 animals developed type 1 diabetes, and eight type 1 diabetes susceptibility loci were mapped, six showing significant linkage (chromosomes 1, 3, 6 [two loci], 12, and 14) and two (chromosomes 2 and 17) suggestive linkage. The chromosomes 6, 12, and 14 intervals were also linked to the severity of islet infiltration by immunocytes, while those on chromosomes 1, 6 (two loci), 14, 17, and a type 1 diabetes-unlinked chromosome 8 interval showed significant linkage to the degree of islet atrophy. Four loci exhibited suggestive linkage to AOO on chromosomes 2 (two loci), 7, and 18 but were unlinked to type 1 diabetes. INS, PTPN22, IL2/IL21, C1QTNF6, and C12orf30, associated with human type 1 diabetes, are contained within the chromosomes 1, 2, 7, and 12 loci. CONCLUSIONS-This study demonstrates that the BBDP diabetic syndrome is a complex, polygenic disease that may share additional susceptibility genes besides MHC class II with human type 1 diabetes

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Examination of the Roles of Iddm26 and Iddm24.1 on the Pathogenesis of Type 1 Diabetes in the BioBreeding Rat

Ph.D

Innovación en empresas de Cuenca-Ecuador: empleo de modelística inteligente en el sector textil

The city of Cuenca-Ecuador, characterized by being an industrial city, specifically those in the textile sector, where its market has proven to be very competitive, predominating tastes and preferences of customers with alternative prices of products or services. The problem of research is presented by the limited supply of designs or models in the garments that are manufactured within this sector. The aim of the study is to develop an intelligent tool for the design and innovation of a men’s garment (jacket), called STIM7, this cutting-edge tool allows companies to reduce uncertainty through expert opinion. Methodologically, this research is of an explanatory nature, connecting on a quantitative level by putting into practice instruments of fuzzy logic. The results achieved is a new jacket design, with qualities of innovation and creativity trying to meet the expectations of the potential client. It is concluded that with this contribution, the textile sector will try to position its product in a competitive market, overcoming the constant changes that occur within it, the model represents an essential factor for the success of an organization through better management business.La ciudad de Cuenca-Ecuador, caracterizada por ser una urbe industrial, específicamente las del sector textil, en donde su mercado ha demostrado ser muy competitivo, predominando gustos y preferencias de los clientes con precios alternativos de productos o servicios. El problema de la investigación se presenta por la poca oferta de diseños o modelos en las prendas de vestir que se fabrican dentro de este sector. El objetivo del estudio es desarrollar una herramienta inteligente para el diseño e innovación de una prenda de vestir para caballero (chaqueta), denominada STIM7, esta herramienta de vanguardia permite a las empresas reducir la incertidumbre mediante la opinión de los expertos. En lo metodológico, esta investigación es de tipo explicativa, conectándose en el plano cuantitativo colocando en práctica instrumentos de la lógica difusa. Los resultados alcanzados es un nuevo diseño de chaqueta, con cualidades de innovación y creatividad tratando de cubrir las expectativas del potencial cliente. Se concluye, que con este aporte, el sector textil tratara de posicionar su producto en un mercado competitivo, superando los constantes cambios que se dan dentro de este, el modelo representa un factor esencial para el éxito de una organización a través de una mejor gestión empresarial

A Functional Polymorphism of Ptpn22 Is Associated with Type 1 Diabetes in the BioBreeding Rat.

The R620W variant of PTPN22 is one of the major genetic risk factors for several autoimmune disorders including type 1 diabetes (T1D) in humans. In the BioBreeding T1D-prone (BBDP) rat, a single nucleotide polymorphism in Ptpn22 results in an A629T substitution immediately C-terminal to the aliphatic residues central to the Ptpn22-C-terminal Src kinase interaction. This variant exhibits a 50% decrease in C-terminal Src kinase binding affinity and contributes to T cell hyperresponsiveness. Examination of BBDP sublines congenic for the Iddm26.2 locus that includes Ptpn22 has not only shown an expansion of activated CD4(+)25(+) T lymphocytes in animals homozygous for the BBDP allele, consistent with enhanced TCR-mediated signaling, but also a decrease in their proportion of peripheral Foxp3(+) regulatory T cells. Furthermore, clinical assessment of both an F2(BBDP × ACI.1u.Lyp) cohort and Iddm26.2 congenic BBDP sublines has revealed an association of Ptpn22 with T1D. Specifically, in both cases, T1D risk is significantly greater in BBDP Ptpn22 homozygous and heterozygous animals. These findings are consistent with a role for rat Ptpn22 allelic variation within Iddm26.2 in the regulation of T cell responses, and subsequently the risk for development of T1D