Genetika最新文献

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/.

Escherichia coli open reading frames ydiO and ydiQRST were identified as genes encoding components of the acyl-CoA dehydrogenase complex of anaerobic fatty acid β-oxidation. Individual or concomitant inactivation of fadE gene, encoding known aerobic acyl-CoA dehydrogenase, and ydiO and/or ydiQRST genes did not affect cellular growth on glucose as a sole carbon source. Aerobic growth on sodium oleate was observed only for the cells with intact fadE gene. With an alternative electron acceptor, the cells possessing intact fadE gene demonstrated anaerobic growth on sodium oleate irrespective of the presence or absence of ydiO and ydiQRST genes. For the fadE-deficient mutants, anaerobic growth on sodium oleate was observed only for cells with intact ydiO and ydiQRST genes, while the fadE/ydiO and fadE/ydiQRST mutants failed to grow under the similar conditions.

SOPH syndrome (Short stature with Optic nerve atrophy and Pelger–Huët anomaly syndrome, OMIM#614800) is an autosomal recessive hereditary disease characterized by the following main clinical symptoms: postnatal hypoplasia, proportionately short stature, facial dysmorphism, micromelia of feet and hands, limp and loose skin, optic nerve atrophy, and Pelger–Huët anomaly of neutrophils. For the first time, this disease was described in Yakuts. The molecular-genetic study showed that its cause in Yakuts is mutation G5741→A in gene NBAS. On the basis of disequilibrium analysis for linkage of ten microsatellite markers flanking the NBAS gene with the disease, the haplotype of the founder chromosome was determined. The age of the mutation in Yakutia was estimated to be about 804 ± 140 years. The frequency of heterozygous carriers of mutation G5741→A (R1914H) in gene NBAS was found, which averaged 13 per 1000 healthy Yakuts.

Genomes of 184 Sinorhizobium meliloti native isolates were studied to test the occurence of islands Sme21T, Sme19T, and Sme80S previously described in the model strain Rm1021. This analysis was conducted using PCR methodology involving specific primers. It was demonstrated that, in the examined geographically distinct populations of S. meliloti from the Northern Caucasus (NCG) and the Aral Sea region (PAG), the strains containing genomic islands were observed with similar frequency (0.55 and 0.57, respectively). Island Sme80S, denoted as an island of “environmental adaptivity,” was identified predominantly (frequency of 0.38) in genomes of strains which exhibited a lower level of salt tolerance and was isolated in PAG, a modern center of introgressive hybridization of alfalfa subjected to salinity. Island Sme21T designated as “ancestral” was observed in genomes of strains isolated in NCG, the primary center of host-plant biodiversity, 10-fold more often than in strains from PAG. An island Sme19T, which predominantly carries genes encoding transposases, was observed in genomes of strains in both populations with average frequency of 0.10. The analysis of linkage disequilibrium (LD) based on the assessment of probability for detection of different islands combinations in genomes revealed an independent inheritance of islands in salt-sensitive strains of various geographic origin. In contrast, the absence of this trend was noted in the majority of the examined combinations of salt-tolerant strains. It was concluded that the structure of chromosome in PAG strains which predominantly possessed a salt-sensitive phenotype was subjected to active recombinant processes, which could predetermine the intensity of microevolutionary processes in bacterial populations and facilitate an adaptation of bacteria in adverse environmental effect.

The distribution of allele and genotype frequencies of Alu(I/D) polymorphic sites in the COL13A1 and LAMA2 genes coding extracellular matrix protein subunits was characterized in an ethnically homogeneous group (Tatars from the Republic of Bashkortostan, Russia). It was established that the frequency of individuals with the COL13A1*D/*D genotype was higher in the senile age period. The LAMA2*I/*D genotype was predisposing to longevity among women. According to the observed results, the frequency of the LAMA2*I/*D genotype was increased in senile individuals older than 90 years. The observed associations can be explained on the basis of the contemporary view by the importance of Alu elements in gene expression regulation at transcriptional and post-transcriptional levels, the involvement of collagen and laminin in maintaining the structure and function of the extracellular matrix, and the relationship between the extracellular matrix state, pathological changes and aging.

On the basis of comparative sequence analysis of 12 honeybee mitochondrial genes, seven genes enabling us to differentiate honeybees subspecies of the A, M, C, O evolutionary lineages were found. Applying comparative sequence analysis of ND2 gene mtDNA as an example on a statistically valid sample size, we showed a high level of differentiating ability of this gene and assumed that each of these seven genes probably can be used for differentiation of the subspecies within four evolutionary lineages.

The genotyping of 75 trees from poplar plantations in St. Petersburg and Leningrad oblast was conducted with microsatellite markers to identify the elite clonal varieties developed by P.L. Bogdanov in the period of 1938–1965. The information about the varieties was lost. The authentic herbarium specimens of poplar clonal varieties preserved at the St. Petersburg State Forest Technical University were used as reference genotypes. According to the results of DNA fingerprinting, we identified the clonal plantations of Populus × newesis Bogd. and Populus × leningradensis Bogd. from the Kartashevskii forest district and the arboretum of the St. Petersburg State Forest Technical University. The identified elite poplar hybrids have a higher frost resistant and a higher growth rate. They are recommended for plantation cultivation in the northwest of Russia.

Ovarian cancer is one of the most insidious of tumors among gynecological cancers in the world. BRCA1 and BRCA2 mutations are associated with high risk of ovarian cancer; however, they are causative only in a fraction of cases. The search for new genes would expand our understanding of the mechanisms underlying malignant ovarian tumors and could help to develop new methods of early diagnosis and treatment of the disease. The present study involved exome sequencing of eight DNA samples extracted from the blood of ovarian cancer patients. As a result of the study, 53057 modifications in one sample were identified on average. Of them, 222 nucleotide sequence modifications in DNA located in exons and splice sites of 203 genes were selected. On the basis of the function of these genes in the cell and their involvement in carcinogenesis, 40 novel candidate genes were selected. These genes are involved in cell cycle control, DNA repair, apoptosis, regulation of cell invasion, proliferation and growth, transcription, and also immune response and might be involved in development of ovarian cancer.

Polymorphism of hordeins encoded by the Hrd A and Hrd B loci was studied using starch gel electrophoresis in 63 landraces of cultivated barley (H. vulgare) and 43 accessions of wild barley (H. spontaneum) from Iran. We identified 35 and 32 Hrd A alleles of H. vulgare and H. spontaneum. The number of Hrd B alleles in these species was 55 and 48, respectively. The frequencies of alleles in the Hrd A and Hrd B loci in cultivated barley varied within the range of 0.0016–0.2816 (Hrd A) and 0.0016–0.1221 (Hrd B). The allelic frequencies in wild barley ranged within 0.0077–0.2170 and 0.0077–0.0815, respectively. Iranian accessions of H. spontaneum and H. vulgare shared some alleles; the number of common alleles was seven for the Hrd A locus and five for the Hrd B locus. These alleles were detected mainly in accessions of wild barley heterozygous or heterogenic for hordein-coding loci. We concluded that the regions close to Zagros mountain range cannot be considered as a barley domestication center. At the same time, Iranian H. spontaneum could have donated some hordein-coding loci to H. vulgare as a result of introgressions occurring because of spontaneous hybridization over the course of the spread of cultivated barley.

We performed an analysis of linkage disequilibrium of alleles of 15 allozyme loci in 35 populations of Scots pine in the Siberian part of the range between 50° and 56° N and 79° and 107° E. We found a significant deviation in the distribution of genotypes of 1–9 pairs of loci in the investigated samples. We established correlations between frequencies of certain pairs of linked loci with ecological conditions and geographical coordinates of habitats of the pine populations. We present the results of comparative analysis of the differences in certain morphological features of trees with significantly predominant genotypes for pairs of linked loci in three isolated populations: in the south of Krasnoyarsk krai, Khakassia, and Tuva.