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Results for “functional genetics”

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At least 127 records · Page 7Linked to original sources
PubMed1982

Immunoglobulin structure and function: genetic control of antibody diversity.

Recent studies of the molecular biological characteristics of lymphoid cells have markedly increased our understanding of how millions of different antibodies can be synthesized by an individual mammal. In particular, studies have shown how antibody genes are arranged and rearranged within B-lymphocyte clones to provide each cell clone with antibody of defined specificity for antigen. The process involves the assembly, from disparate genetic elements, of a complete antibody gene that will code for an antibody protein. The assembly process, in itself, also provides mechanisms for generating the diversity of antibody variable region structure (that part of an antibody molecule that actually binds antigen) that is essential to a full role for humoral immunity in host defense mechanisms. Specifically, the diversity of structure characteristic of mature antibodies derives from 3 distinct mechanisms: innate variability of germ-line genes; mismatching of individual gene segments during their somatic rearrangement leading to junctional diversity; and somatic mutation in variable region genetic material during or after the rearrangement. Thus, it is now clearly understood that several processes are involved in explaining the origin of the antigen-combining diversity of antibody proteins. Certain "lottery-like" aspects of these genetic processes add to the combinatorial possibilities that are characteristic of the humoral immune system.

Animals↗
PubMed1996

On genetic map functions.

Various genetic map functions have been proposed to infer the unobservable genetic distance between two loci from the observable recombination fraction between them. Some map functions were found to fit data better than others. When there are more than three markers, multilocus recombination probabilities cannot be uniquely determined by the defining property of map functions, and different methods have been proposed to permit the use of map functions to analyze multilocus data. If for a given map function, there is a probability model for recombination that can give rise to it, then joint recombination probabilities can be deduced from this model. This provides another way to use map functions in multilocus analysis. In this paper we show that stationary renewal processes give rise to most of the map functions in the literature. Furthermore, we show that the interevent distributions of these renewal processes can all be approximated quite well by gamma distributions.

Chromosome Mapping↗
PubMed2001

Genetic disorders of neonatal respiratory function.

Genetic risk for respiratory distress in infancy has been recognized with increasing frequency in neonatal intensive care units. Reports of family clusters of affected infants and of ethnic- and gender-based respiratory phenotypes point to the contribution of inheritance. Similarly, different outcomes among gestationally matched infants with comparable exposures to oxygen, mechanical ventilation, or nutritional deficiency also suggest a genetic risk for respiratory distress. Examples of inherited deficiency of surfactant protein B in both humans and genetically engineered murine lineages illustrate the importance of identifying markers of genetic risk. In contrast to developmental, inflammatory, or nutritional causes of respiratory distress that may resolve as infants mature, genetic causes result in both acute and chronic (and potentially irreversible) respiratory failure. The availability of clinically useful genetic markers of risk for respiratory distress in infancy will permit development of rational strategies for treatment of genetic lung disorders of infancy and more accurate counseling of families whose infants are at genetic risk for development of respiratory distress at birth or during early childhood. We review examples of genetic variations known to be associated with or cause respiratory distress in infancy.

Animals↗
PubMed2004

Mining functional modules in genetic networks with decomposable graphical models.

In recent years, graphical models have become an increasingly important tool for the structural analysis of genome-wide expression profiles at the systems level. Here we present a new graphical modelling technique, which is based on decomposable graphical models, and apply it to a set of gene expression profiles from acute lymphoblastic leukemia (ALL). The new method explains probabilistic dependencies of expression levels in terms of the concerted action of underlying genetic functional modules, which are represented as so-called "cliques" in the graph. In addition, the method uses continuous-valued (instead of discretized) expression levels, and makes no particular assumption about their probability distribution. We show that the method successfully groups members of known functional modules to cliques. Our method allows the evaluation of the importance of genes for global cellular functions based on both link count and the clique membership count.

Gene Expression Profiling↗
PubMed2005

Nonlinear protein degradation and the function of genetic circuits.

The functions of most genetic circuits require a sufficient degree of cooperativity in the circuit components. Although mechanisms of cooperativity have been studied most extensively in the context of transcriptional initiation control, cooperativity from other processes involved in the operation of the circuits can also play important roles. In this work, we examine a simple kinetic source of cooperativity stemming from the nonlinear degradation of multimeric proteins. Ample experimental evidence suggests that protein subunits can degrade less rapidly when associated in multimeric complexes, an effect we refer to as "cooperative stability." For dimeric transcription factors, this effect leads to a concentration-dependence in the degradation rate because monomers, which are predominant at low concentrations, will be more rapidly degraded. Thus, cooperative stability can effectively widen the accessible range of protein levels in vivo. Through theoretical analysis of two exemplary genetic circuits in bacteria, we show that such an increased range is important for the robust operation of genetic circuits as well as their evolvability. Our calculations demonstrate that a few-fold difference between the degradation rate of monomers and dimers can already enhance the function of these circuits substantially. We discuss molecular mechanisms of cooperative stability and their occurrence in natural or engineered systems. Our results suggest that cooperative stability needs to be considered explicitly and characterized quantitatively in any systematic experimental or theoretical study of gene circuits.

Bacteria↗
PubMed2005

Estimates of genetic covariance functions for growth of Angus cattle.

Estimates of covariance functions and genetic parameters were obtained for growth of Angus cattle from birth to 820 days of age. Data comprised 84,533 records on 20,731 animals in 43 herds, with a high proportion of animals with 4 or more weights recorded. Changes in weights were modelled through random regression on orthogonal polynomials of age at recording. A total of 11 combinations of quadratic, cubic, quartic and quintic polynomials to model direct and maternal genetic effects and permanent environmental effects were considered. Results showed good agreement for all models at ages with many records, but differed at the highest ages and at very early ages with few weights available. Cubic polynomials appeared to be most problematic. The order of polynomial fit for permanent environmental effects of the animal dominated estimates of phenotypic variances and mean squares for residual errors. A model fitting a quartic polynomial for these effects and quadratic polynomials for the other random effects, appeared to be the best compromise between detailedness of the model which could be supported by the data, plausibility of results, and fit, measured as mean square error.

Age Factors↗