Genetic characterization of the Latvian local goat breed and genetic traits associated with somatic cell count.

The Latvian local goat (LVK) breed represents the only native domestic goat breed in Latvia, but its limited population places it within the endangered category. However, the LVK breed has not yet undergone a comprehensive genetic characterization. Therefore, we completed whole genome sequencing to reveal the genetic foundation of the LVK breed while identifying genetic traits linked to the somatic cell count (SCC) levels. The study included 40 genomes of LVK goats sequenced to acquire at least 35x or 10x coverage. A Principal component analysis, a genetic distance tree, and an admixture analysis showed LVK's similarity to some European breeds, such as Finnish Landrace, Alpine, and Saanen, which aligns with the breed's history. An analysis of genome-wide heterozygosity, nucleotide diversity, and LD analysis indicated that the LVK population exhibits substantial levels of genetic diversity. LVK genome was dominated by short runs of homozygosity (ROHs, ≤ 500 kb) with a median length of 25 kb. With FROH 2.49%, average inbreeding levels were low; however, FROH ranged broadly from 0.13 to 12.2%. With the exception of one pure-blood breeding buck exhibiting FROH of 9.3% and FSNP of 8.5%, animals with at least 66% LVK ancestry showed moderate or no inbreeding. Overall, this study demonstrated that the LVK goats can be differentiated from imported breeds, although the population has a complex genetic structure. We were able to identify potential genetic traits associated with SCC levels, although the kinship of the animals and the heterogenic substructure of the population might have largely influenced the association analysis. We identified 26 genetic variants associated with SCC levels, which included the potentially relevant SNP rs662053371 in the OSBPL8 gene, indicating a potential signal linked to lipid metabolism in goats. To conclude, these findings present valuable insight into the genetic structure of the LVK breed for the conservation of local genetic resources.

Determination of the obesity-associated gene variants within the entire FTO gene by ultra-deep targeted sequencing in obese and lean children.

BACKGROUND: The Fat mass and obesity-associated gene (FTO) was the first gene reliably associated with body mass index in genome-wide association studies on a population level. At present, the genetic variations within the FTO gene are still the common variants that have the largest influence on body mass index. METHODS: In the current study, we amplified the entire FTO gene, in total 412 Kbp, in over 200 long-range PCR fragments from each individual, from 524 severely obese and 527 lean Swedish children, and sequenced the products as two DNA pools using massive parallel sequencing (SOLiD). RESULTS: The sequencing achieved very high coverage (median 18 000 reads) and we detected and estimated allele frequencies for 705 single nucleotide polymorphisms (SNPs) (19 novel) and 40 indels (24 novel) using a sophisticated statistical approach to remove false-positive SNPs. We identified 19 obesity-associated SNPs within intron one of the FTO gene, and validated our findings with genotyping. Ten of the validated obesity-associated SNPs have a stronger obesity association (P<0.007) than the commonly studied rs9939609 SNP (P<0.012). CONCLUSIONS: This study provides a comprehensive obesity-associated variation map of FTO, identifies novel lead SNPs and evaluates putative causative variants. We conclude that intron one is the only region within the FTO gene associated with obesity, and finally, we establish next generation sequencing of pooled DNA as a powerful method to investigate genetic association with complex diseases and traits.

Stronger association of common variants in TCF7L2 gene with nonobese type 2 diabetes in the Latvian population.

Polymorphisms in the gene coding for transcription factor 7 like 2 (TCF7L2) are recognized as the strongest common genetic risk factors for type 2 diabetes (T2D) across multiple ethnicities. This study was conducted to evaluate an association between TCF7L2 variants and diabetes susceptibility in the population of Latvia. We genotyped 4 single nucleotide polymorphisms (SNP) rs7901695, rs7903146, rs11196205 and rs12255372 in 1 093 controls and 1 043 diabetic subjects. Association with T2D was found for 3 SNPs rs7901695, rs7903146 and rs12255372 in the whole sample (under an additive genetic model, the adjusted odds ratios (OR) were 1.26, 95% CI [1.08-1.48], P=0.003; OR=1.32, 95% CI [1.12-1.55], P=0.001 and OR=1.35, 95% CI [1.15-1.60], P=0.0004 respectively). In addition observed effects on T2D susceptibility for analysed SNPs were higher among subjects with BMI under 30 kg/m². The impact of TCF7L2 variation on T2D risk in Latvian population is compatible with that demonstrated by a range of studies conducted in various ethnic groups.

Use of the fluorescent probe DSM in studies of the structural and functional changes of the erythrocyte membrane.

We have investigated the binding of n-toluenesulfonate-4-(n-dimethylaminostyrene)-1-methylpyridinium (DSM) to human and animal erythrocyte membrane. It was discovered the spectral characteristics and binding parameters of the probes differ in the norm and in various pathologies, at changing adrenoreactivity of the animal organism. It is concluded that the probe can be used to assess the changes in membrane properties and in the beta-adrenoreceptive function of both the erythrocytes and the organism as a whole.

Modification of the activity of mitochondrial monoamine oxidases in vitro and in vivo.

Treatment of bovine brain mitochondrial membranes with iproniazid (Ip) (1 mM, 15 min) inhibited monoamine oxidase (MAO) activity (substrates: 5-hydroxytryptamine, tyramine, dopamine) and significantly (about 7-fold) increased histamine deaminating activity (HDA). A selective inhibitor of MAO-A clorgyline (contrary to deprenyl) prevented the increase in HDA. Ip (200 mg/kg; within 10-16 h after parenteral administration) markedly (about 6-fold) increased the level of the HDA) in brain mitochondria of mice and guinea pigs. At the same time, a decrease in content of histamine (Hi) and increase in content of 5-hydroxytryptamine was noted in the brains of mice. In anesthetized and non-anesthetized guinea pigs Ip decreased (or prevented) the bronchoconstriction and toxic effects caused by Hi. The antihistamine effects of Ip are apparently due to its being able to induce reversible qualitative alteration (transformation) of the catalytic activity of the membrane-bound MAO of type A, which acquires as a result of this transformation potent HDA.

[Effect of temperature and composition of frozen solutions on the rate of peroxidase oxidation of 2,3-dimethyl-1,4-naphthoquinol-1-dimethylphosphate]. / Vliianie temperatury i sostava zamorozhennogo rastvora na skorost' kataliziruemogo peroksidazoi okisleniia 2,3-dimetil-1,4-naftokhinol-1-dimetilfosfata.

The horseradish peroxidase-catalyzed oxidation of 2.3-dimethyl-1.4-naphthoquinol-1-dimethylphosphate by hydrogen peroxide was investigated within the temperature range of +20 divided by -35 degrees. The increase in the concentration of the buffer solution accelerated the reaction in liquid solutions at 0 degrees and 20 degrees. The unusual shapes of the curves of temperature dependences of the reaction rate in frozen solutions of different composition can probably be due to temperature variations in some physico-chemical parameters of the system under study.

[Comparative study of the effect of inhibitors of monoamine oxidase and ftorafur on the growth of de-differentiated astrocytoma]. / Sravnitel'noe izuchenie deistviia ingibitorov monoaminoksidazy i ftorafura na rost dedifferentsirovannoi astrotsitomy

To evaluate the possible antitumour effect of intensified deposition of serotonin in the region of localization of the tumour caused by a pharmacological preparation studies of the effect of inhibitors of monoamine oxidase transamine and N2N2-dibenzylhydrazide of DL-malic acid on rat's cerebellum tumour de-differentiated by astrocytoma (strain No 101/12) were carried out. The effect of inhibitors of monoamine oxidase was compared with that of antiblastic preparation of phthorafur. Differences in the mechanisms of action of pharmacological agents referred to above are shown. It was established that inhibitors of monoamine oxidase administered against the background of the developing tumour caused a considerable reduction in its weight and prononced dystrophic and necrotic changes.