Functional linear models for region-based association analysis

Regional association analysis is one of the most powerful tools for gene mapping because instead analysis of individual variants it simultaneously considers all variants in the region. Recent development of the models for regional association analysis involves functional data analysis approach. In the framework of this approach, genotypes of variants within region as well as their effects are described by continuous functions. Such approach allows us to use information about both linkage and linkage disequilibrium and reduce the influence of noise and/or observation errors. Here we define a functional linear mixed model to test association on independent and structured samples. We demonstrate how to test fixed and random effects of a set of genetic variants in the region on quantitative trait. Estimation of statistical properties of new methods shows that type I errors are in accordance with declared values and power is high especially for models with fixed effects of genotypes. We suppose that new functional regression linear models facilitate identification of rare genetic variants controlling complex human and animal traits. New methods are implemented in computer software FREGAT which is available for free download at http://mga.bionet.nsc.ru/soft/FREGAT/.     

A novel method of multiple alignment of biopolymer sequences

A novel algorithm for multiple alignment of biological sequences is suggested. At the first step the DotHelix procedure is employed for construction of motifs, i.e. continuous fragments of local similarity of various “thickness” and strength, and then these motifs are concatenated into chains consistent with the order of letters in the sequences. The algorithm is implemented in the MA-Tools program of the GeneBee package. An example illustrating the effectivity of the algorithm is presented.     

How costly is clutch formation in the Audouin's Gull Larus audouinii?

During the Audouin's Gull's breeding season at the Ebro Delta in 1993, 24 fresh eggs from eight three-egg clutches (modal clutch-size) were collected at the peak of the laying period. Eggs were processed to obtain formalin-fixed yolks, which were halved and stained using the potassium dichromate method. Digitized images of the yolks were examined to assess the daily rates of yolk deposition. We used these data in combination with egg compositional analysis to build a model of energy demands during the formation of an average clutch in Audouin's Gull. To show how the different parameters of clutch formation affect the daily energy investment peak, we performed a simulation analysis in which the rapid yolk development (RYD) period, the follicle triggering interval (FTI), the laying interval (LI) and the albumen synthesis period (ASP) were allowed to vary simultaneously. In our sample, the mean RYD period was seven days with a range from six to eight days. There were no significant differences in yolk volume among eggs in a clutch, but albumen volume was significantly smaller in third eggs. According to our model the albumen synthesis of the a-egg coincides with the energy demand peak for clutch formation. This peak represents an increase by ca. 42% in female energy requirements. Values obtained from the simulation analysis showed that only the ASP of the a-egg and the RYD durations of the second and third follicles produced noticeable reductions in peak energy investment. We predict that in gulls, whose laying intervals seem to be kept constant, significant increases of the durations of the RYD periods of second and third eggs, or even significant reductions of yolk size of these eggs, may operate simultaneously to match the energy demands during clutch formation to the prevailing food conditions.     

Genetic organization of transfer region of F-like plasmid pAP18-1

The results of complementation analysis of nitrosoguanidine-induced mutants of F-like drd-plasmid pAP18-1 (Tc, ColV) testified to the existence of at least 3 tra regions (tra1, tra2, tra3) and regulating locus fin V in the genome of this plasmid. By means of molecular cloning of tra2 region and locus fin V of plasmid pAP18-1drd were located in Sall-fragment f5 (3.9 MD).     

Differences between some properties of acetylated and nonacetylated forms of HMG1 protein

There are data suggesting that HMG1 protein may be involved in DNA replication. Recently we have found that only the acetylated form of the protein generates tetramers, stimulates the activity of DNA polymerase alpha (EC 2.7.7.7) (with activated DNA as a template) and forms a specific complex with it. This paper compares some properties of the acetylated and nonacetylated forms of HMG1 protein and shows that it is only the acetylated form which serves as a histone assembly factor, increases the melting temperature of poly d[(A-T)] and stimulates the activity of DNA polymerase alpha when histone H1-depleted chromatin is used as a template.     

Hyperbaric oxygenation in the comprehensive therapy of patients with rheumatoid arthritis (clinico-immunologic study)

For 35 of 50 patients with rheumatoid arthritis traditional drug therapy was a minor success for a long time. Without any modifications of the drug therapy every patient went through a course of hyperbaric oxygenation (HBO): 21 sessions under 1.7 ata for 40 min. Good clinical results both immediate and remote have been obtained. The effect of HBO on the immune system of the patients has intensified the suppressive function of T-lymphocytes (especially with systemic symptoms of the disease), normalized cell-bound immunity and decreased the serum concentration in immune complexes.     

Regulation of apolipoprotein expression]

Recent data and concepts on the structure and functioning of apolipoprotein genes as well as on the role of hereditary factors in pathogenesis of atherosclerosis are reviewed. The most important variants of inherited disorders in the system of apolipoproteins promoting the development of atherosclerosis are considered. Special attention is paid to the RFLP of apolipoprotein genes which serves as a peculiar genetic background, increasing probability of the atherosclerosis development in certain individuals.     

Turnover of cell surface-bound capsular polysaccharide in Staphylococcus aureus

The capsular polysaccharide (CPS) of Staphylococcus aureus strain Smith was labelled by growth of bacteria in the presence of radioactive N-acetylglucosamine and was separated from labelled cell wall components by affinity chromatography on wheat germ agglutinin following dissolution of the cells by lysostaphin. The products were partially characterised chemically and immunochemically. Similar labelled components were found in the culture fluid during growth. In a pulse-chase experiment, cell-bound CPS was released continuously into the culture fluid at the same rate as cell wall turnover and there was no evidence of direct excretion of CPS.