Structural Gene Loci Research Articles

Revana: a comprehensive tool for regulatory variant analysis and visualization of cancer genomes.

As non-coding driver mutations move more into the focus of cancer research, a comprehensive and easy-to-use software solution for regulatory variant analysis and data visualization is highly relevant. The interpretation of regulatory variants in large tumor genome cohorts requires specialized analysis and visualization of multiple layers of data, including for example breakpoints of structural variants, enhancer elements and additional available gene locus annotation, in the context of changes in gene expression. We introduce a user-friendly tool, Revana (REgulatory Variant ANAlysis), that can aggregate and visually represent regulatory variants from cancer genomes in a gene-centric manner. It requires whole-genome and RNA sequencing data of a cohort of tumor samples and creates interactive HTML reports summarizing the most important regulatory events. Revana is implemented in R and JavaScript. It is available for download as an R package under <https://github.com/KiTZ-Heidelberg/revana>. Sample results can be viewed under <https://github.com/KiTZ-Heidelberg/revana-demo-report> and a short walkthrough is available under <https://github.com/KiTZ-Heidelberg/revana-demo-data>. Supplementary data are available at Bioinformatics online.

Heterogeneity is not always a source of noise: Stochastic gene expression in regulatory heterozygote.

Zygosity of diploid genome (i.e., degree to which two parental alleles of a gene have varied genetic sequences) adds another dimension to stochastic gene expression. The allelic imbalance in chromatin accessibility or divergence in regulatory sequences leads to fitness effects but the quantitative aspects thereof are largely left unexplored. We investigate diploid gene expression systems with homozygous (the same) and heterozygous (varied) combination of alleles in cis-regulatory sequences, not in structural gene loci, and characterize the zygosity-associated stochastic fluctuations in protein abundance. An emerging feat of heterozygosity is its counterintuitive capacity for genetic noise control. Especially when the noise is dominantly contributed to by the fluctuations in duty cycle ("reliability") rather than in process speed ("productivity") of gene expression machinery, its interallelic discrepancy acts to reduce the gene expression noise. These findings offer a novel insight into the rich repertoire of balancing selection enriched in the regulatory elements of immune response genes.

Genetic differentiation and phylogeny of 27 sheep populations based on structural gene loci

To explore the genetic divergence and phylogeny of Chinese indigenous sheep breeds, in the current study, we analyzed the polymorphisms of 5 structural loci in ten sheep populations, including Sishui Fur, Sunite, Wurank, Bayinbuluke, Altay, Small-Tailed Han, Wadi, Tan, Tong and Hu sheep. The data were then compared with those from an additional 13 Asian and 4 European sheep populations acquired by the same experimental method. Based on the genetic distance and the results of a cluster analysis, we constructed the phylogenetic relationship of 27 populations. The results showed that the sheep populations in this study could be classified into four genetic groups: “Mongolian”, “Tibetan”, “South-Southeast Asian” and “European” sheep groups. All 10 Chinese sheep breeds belonged to the “Mongolian sheep” lineage; however, Finnish Landrace sheep and Yunnan sheep could not be classified into any of the four groups. These results could provide a good reference for the protection and utilization of primary breed resources in China and phylogenic research on Asian sheep populations.

Quantitative genetic study of the circulating osteopontin in community-selected families

The study assessed contribution of genetic factors to variability of osteopontin (OPN) levels. Evidence of association of OPN levels with polymorphisms in its structural gene and integrin-binding sialoprotein gene loci was obtained. The results motivate research of OPN-related proteins and genes with respect to biomineralization and other biological processes. OPN is a major phosphoprotein in bone, which plays key role in regulation of bone mineralization process. It is considered as a promising biomarker for osteoarthritis and osteoporosis, and various other pathological conditions. However, the contribution of genetics and other confounding factors to OPN circulating levels variation in general population has never been specifically determined. The main aims of the present study included (1) evaluation of the putative genetic and familial factors' effect on OPN variability and (2) testing the hypothesis that OPN plasma levels are associated with the genetic polymorphisms in its structural gene locus (SPP1) and in integrin-binding sialoprotein gene locus (IBSP). To address these questions, we used a family-based sample of 925 apparently healthy Caucasian individuals. Association of OPN levels with three SNPs in each of the two selected gene loci was explored using pedigree disequilibrium tests. Some 58% and 13% of the OPN levels variability were attributable to genetic factors and common spouse environment, respectively. Three SNPs showed nominally significant association with OPN (p < 0.05). Of these, rs2616262 linked to IBSP promoter region remained significant after correction for multiple testing (p = 0.003). Significant association of this SNP and rs10516799 (distal segment of SPP1) with OPN was confirmed in several statistical tests. Using a special modification of variance component analysis, we examined gene-gene and gene-sex interaction effects, but found non-significant confirmation for these hypotheses. Further studies are required to confirm the observed results and to explore the underlying molecular and physiological mechanisms.

Genetic determinants of circulating levels of tumor necrosis factor receptor II and their association with TNF-RII gene polymorphisms

Background Tumor necrosis factor alpha (TNFα) is a cytokine involved in inflammatory, immune, and metabolic events. TNFα signals are mediated through activation of two receptors, one of which is tumor necrosis factor receptor TNF-RII. Objective To examine the effects of genetic and environmental factors on TNF-RII plasma concentration and its association with polymorphisms in the TNF-RII gene locus. Methods The levels of sTNF-RII were determined in 897 individuals. The association between sTNF-RII and polymorphisms in its structural gene locus was examined by pedigree-based association analyses (PDT) and transmission disequilibrium tests (TDTs). Results 49.57% of the adjusted sTNF-RII variability was attributable to genetic factors. sTNF-RII plasma levels were nominally associated with the genomic region spanning TNF-RII promoter and the first intron, represented by rs976881 ( p = 0.029). Although after correction for multiple testing this PDT signal formally did not reach statistical significance, it was reflected also in series of TDTs and further confirmed by association observed for haplotype of rs976881 with rs590368 (nominal p = 0.006) and by ANOVA. Conclusions sTNF-RII plasma concentration is determined by both genetic and environmental factors. Our results suggest association between sTNF-RII levels and polymorphisms in vicinity to TNF-RII promoter region. This finding requires further thorough validation in other populations.

Gene flow among sheep breeds of mongolian group in China

Gene flow was analyzed among four sheep breeds of Mongolian Group in China using structural gene loci and microsatellite markers.Results showed that genetic differentiation was 0.0164-0.0455 by using structural loci, and was 0.0107-0.0239 by using microsatellite loci.This illustrated that most variations existed within breeds and genetic differentiation level was very low among sheep breeds of Mongolian Group in China.There was substantial Gene flow among the breeds as estimated by the structural loci (Nm=7.971) or the microsatellite method(Nm=15.732).There was no direct relationship between genetic differences from breeds and geographical distances.It is concluded that genetic differentiation of sheep breeds of Mongolian Group in China is mainly the result of natural selection (different living conditions).

Association of apolipoprotein E (RFLP) polymorphism with myopia

BACKGROUND: Myopia or nearsightedness is a spherical error of refraction, whereby the images are focused in front of retina. Eye, being an organ rich in activated oxygen species, requires a high level of antioxidants to protect the unsaturated fatty acids. Apolipoprotein E (APOE) is one of the proteins that is produced by Muller cells within the retina and is also endowed with antioxidant properties. Genetic polymorphism of APO E is controlled by three common alleles e3, e2 and e4 and rare e1, e4v at the APOE structural gene locus. Different isoforms of APO E differ in their antioxidant properties, and the e4 allele has lesser ability to combat oxidative stress. AIMS: Myopia being a disease influenced by oxidative stress, the present study was undertaken to find association of myopia with APO E polymorphism. MATERIALS AND METHODS: A total of 187 myopic cases and 192 controls were genotyped for apolipoprotein E polymorphism. RESULTS: In both controls and myopic cases, E3/3 genotype was found to be the most frequent one. There was an increase in E3/4 genotype frequency among male probands, high myopia cases and probands with early age at onset, suggesting that the E3/4 genotype might confer risk for myopia development. CONCLUSION: This association with E3/4 genotype might predispose susceptible individuals to develop high myopia and early onset myopia.

On gene pool divergence of the brown hare (Lepus europaeus, Pallas) in Vojvodina

Today it is widely accepted that a conservation of genetic diversity increases chances of animal survival. The aim of this study was investigation of gene pool divergence of the brown hare (Lepus europaeus) in Vojvodina. Allozymic diversity of 60 brown hares from different localities in Vojvodina was studied by polyacrylamide and starch gel electrophoresis at 31 putative structural gene loci. Only five loci: Idh-2, Pgd, Pgm, Es-1 and Es-D were polymorphic, possessing 2 to 6 different alleles. The value of average heterozygosity (Ho) was 0.0427, while polymorphism (P99%) was 8.4%. Nei's values of genetic distance (ranged from 0.000 to 0.029) and modified Roger's distance (ranged from 0.030 to 0.181) were calculated among hare populations. Apart from the relatively high values of heterozygosity and polymorphism, the nuclear gene pool diversity of brown hare population in Vojvodina based on allozyme variation is low and corresponds to the data obtained for the populations in Austria and Central Europe.

Genetic characterization of the peptidases of Polistes versicolor (Hymenoptera: Vespidae).

Starch gel electrophoresis with L-leucyl-beta-naphthylamide as substrate revealed five aminopeptidases in extracts of Polistes versicolor. These enzymes are presumably products of five structural gene loci. All but Lap1 aminopeptidases exhibited differential distribution in the developmental stages and in the tissues. Five dipeptidases were revealed with different dipeptides. These enzymes exhibited significant differences in their substrate preferences, but a more homogeneous distribution throughout ontogenetic developmental stages than did aminopeptidases. Electrophoretic variants of Lap4 and PepA2 were detected and although a low intralocus heterozygosity was found due to the low frequency of these variants, phenotypical segregation observed at these loci in pupae extracts of some colonies points to the occurrence of more than one egg-laying female. Otherwise, the detection of Lap4 allozyme restricted to nests of one area suggests low dispersion ability of the adults of Polistes versicolor.

QTL Mapping for Enzyme Activity and Thermostability of .BETA.-Amylase in Barley (Hordeum vulgare L.).

We investigated the QTLs for the enzyme activity and thermostability in β-amylase in barley using two doubled haploid line (DHL) populations. QTLs for the enzyme activity were detected on chromosomes 1H and 2H in the Steptoe/Morex DHLs and on chromosome 5H in the Harrington/TR306 DHLs, respectively. Some of these QTLs were close to the QTLs for the diastatic power and grain protein which represent malt quality characteristics. We observed two QTLs for the thermostability in the Steptoe/Morex DHLs. Position of one major QTL was the same as that of the β-amylase structural gene locus on chromosome 4H, suggesting that thermostability is controlled by multiple alleles of the locus. The other QTL with a negligible effect was located on the short arm of chromosome 2H. However, no QTLs were observed in the Harrington/TR306 DHLs because the difference in the thermostability value in the DHLs was not appreciable.

Genetic structure of population of Bacillus cereus and B. thuringiensis isolates associated with periodontitis and other human infections.

The genetic diversity and relationships among 35 Bacillus cereus and Bacillus thuringiensis isolates recovered from marginal and apical periodontitis in humans and from various other human infections were investigated using multilocus enzyme electrophoresis. The strains were isolated in Norway, except for three strains isolated from periodontitis patients in Brazil. The genetic diversity of these strains was compared to that of 30 isolates from dairies in Norway and Finland. Allelic variation in 13 structural gene loci encoding metabolic enzymes was analyzed. Twelve of the 13 loci were polymorphic, and 48 unique electrophoretic types (ETs) were identified, representing multilocus genotypes. The mean genetic diversity among the 48 genotypes was 0.508. The genetic diversity of each source group of isolates varied from 0.241 (periodontal infection) to 0.534 (dairy). Cluster analysis revealed two major groups separated at a genetic distance of greater than 0.6. One cluster, ETs 1 to 13, included solely isolates from dairies, while the other cluster, ETs 14 to 49, included all of the human isolates as well as isolates from dairies in Norway and Finland. The isolates were serotyped using antiflagellar antiserum. A total of 14 distinct serotypes were observed. However, little association between serotyping and genotyping was seen. Most of the strains were also analyzed with pulsed-field gel electrophoresis, showing the presence of extrachromosomal DNA in the size range of 15 to 600 kb. Our results indicate a high degree of heterogeneity among dairy strains. In contrast, strains isolated from humans had their genotypes in one cluster. Most strains from patients with periodontitis belonged to a single lineage, suggesting that specific clones of B. cereus and B. thuringiensis are associated with oral infections.

Studies on the European hare. 55. Population genetics of Bulgarian brown hares Lepus europaeus: allozymic diversity at zoogeographical crossroads

Allozymic variability of 157 brown hares Lepus europaeus (Pallas, 1778) from eight sampling localities in Bulgaria was studied by horizontal starch gel electrophoresis of 50 putative structural gene loci.

Gene pool variability of a golden eagle ( Aquila chrysaetos) population from the Swiss Alps

Numbers of golden eagles ( Aquila chrysaetos) were severely reduced by hunting towards the end of the last century over large parts of central Europe. To estimate the genetic variation in a currently thriving golden eagle population from the Swiss Alps, organ samples of 15 carcasses, collected during 1975–1993, were used for electrophoretic analysis of 31 isozyme systems encoding for 37 putative structural gene loci. Average heterozygosity ( H e =3.4%) was within the range found in various other bird taxa, despite a probably low “effective population size” of this population early in this century. Nevertheless, the somewhat reduced rate of polymorphism ( P 99%=10.8) and the mean number of alleles ( A=1.11) may indicate reduced genetic variability, although the H:P ratio was within the range of many non-endangered avian species.

Heterogeneity of ApolipoproteinE polymorphisE and its Isoforms in Five caste groups of Punjab, India

Genetic polymorphism of ApolipoproteinE is controlled by three connon alleles(E2,E3 and E4) and some rare alleles (e.g. El, E4v etc;) at Apo E structural gene locus and may be demonstrated by Iso-electric Focussing, Density gradient poly-acrylamide gel electrophoresis and Imunoblotting techniques et;. The common ApoE isoform E2 (arg158-cys) and E4 (cys112-arg) differ functionally from the parent E3 isoform, explaining their effects on the normal variation of Plasma Lipoprotein concentrations and their association with Hyperlipidemic conditions. Apolipoprotein genotypes were determined in five endogamous caste groups in a sample of 150 Indians from Punjab. ApoE have been observed at respective allele frequencies 0.077, 0.807 and 0.115 in these population groups of Banias, 0.050, 0.825 and 0.125 in Brahmins, 0.057, 0.846 and 0.097 for Jat Sikhs, 0.060, 0.800 and 0.140 in Khatris and 0.035, 0.839 and 0.125 for mixed group ‘Others’. Apo E3 (ApoE3,3 and ApoE3,4) subjects had higher frequencies than ApoE4 (ApoE4,3 and ApoE4,4) and ApoE2 (ApoE2,2 and ApoE3,2) subjects in all the groups studied suggesting the low prevalence of Alzheimer's disease and CHD's. The estimated ApoE allele frequencies were combined with data from other studies of the World to outline the total map of ApoE allele frequency distribution from Europe to Asia.

First Description of Two Genetic Loci in Leuciscus cephalus (Cyprinidae) from Italy

Abstract The biochemical-genetic analysis of 19 enzyme systems coded by 33 structural gene loci in the diploid Leuciscus cephalus have revealed the existence of two genetic loci never described in other cyprinid fishes. The electromorphs of mitochondrial aspartate aminotransferase (mAAT) and fumarate hydratase (FH) in larvae and in different adult tissues of Leuciscus cephalus suggest that these enzymes are coded by two loci each, at variance of available literature data on cyprinids, in which a single structural locus is known to code the mAAT and FH enzymes. These observations are confirmed for the adults of 8 additional Italian cyprinids.

Isozymes in Larrea divaricata and Larrea tridentata (Zygophyllaceae): a study of two amphitropical vicariants and autopolyploidy.

Electrophoretic variants for seven isozyme systems - probably encoded by 18 structural gene loci - in diploid populations of Larrea divaricata and diploid and tetraploid populations of its North American vicariant derivative L. tridentata were assayed by polyacrilamide and starch gel electrophoresis. High molecular similarity of diploid and tetraploid cytotypes of L. tridentata supports the hypothesis of interracial autopolyploidy. The absence of fixed heterozygosity and additive profiles indicates a low level of divergence between the parental diploids and the tetraploids. The phenogram based on the I coefficient showed the similarities between the populations of diploid L. divaricata and also between the diploid populations of L. tridentata. Both groups of diploid populations were more distantly connected to tetraploid L. tridentata.

Temporal Variation in Genetic Diversity and Structure of a Lotic Population of Burkholderia (Pseudomonas) cepacia

The genetic structure and temporal patterns of genetic diversity in a population of Burkholderia (Pseudomonas) cepacia, isolated from a southeastern blackwater stream, were investigated by multilocus enzyme electrophoresis. Allelic variation in seven structural gene loci was monitored at a single stream location at 0, 6, 12, and 24 h and at 2, 4, 8, 16, and 32 days. Over the length of the study, 217 isolates were collected, from which 65 unique electrophoretic types (ETs) were identified. Most of these ETs were present at only one or two time periods and were considered transients; however, one resident ET was particularly abundant (64 of the 217 isolates [29.4%]) and was found at all time points except day 32. The mean genetic diversity of the entire population was 0.520, and the index of association (a measure of multilocus linkage disequilibrium) was 1.33. These results, taken in conjunction with a previous study focusing on spatial patterns of genetic diversity in lotic B. cepacia, show that these bacterial populations exhibit greater variability among sites than within a site over time, suggesting relative stability over short time periods.

Genetic structure of a lotic population of Burkolderia (Pseudomonas) cepacia

The genetic structure of a population of Burkholderia (Pseudomonas) cepacia isolated from a southeastern blackwater stream was investigated by using multilocus enzyme electrophoresis to examine the allelic variation in eight structural gene loci. Overall, 213 isolates were collected at transect points along the stream continuum, from both the sediments along the bank and the water column. Multilocus enzyme electrophoresis analysis revealed 164 distinct electrophoretic types, and the mean genetic diversity of the entire population was 0.574. Genetic diversity values did not vary spatially along the stream continuum. From a canonical discriminant analysis, Mahalonobis distances (measurements of genetic similarity between populations) revealed significant differences among the subpopulations at the sediment sampling points, suggesting bacterial adaptation to a heterogeneous (or patchy) microgeographical environment. Multilocus linkage disequilibrium analysis of the isolates revealed only limited association between alleles, suggesting frequent recombination, relative to binary fission, in this population. Furthermore, the dendrogram created from the data of this study and the allele mismatch distribution are typical of a population characterized by extensive genetic mixing. We suggest that B. cepacia be added to the growing list of bacteria that are not obligatorily clonal.

The sucrase-isomaltase structural gene (Si-s) and a regulatory gene (Si-r) are closely linked to esterase-26 (Es-26) on mouse Chromosome 3

A cDNA clone of the rat sucrase-isomaltase (SI) structural gene detected two distinct patterns of DNA fragments on Southern blots of mouse DNA. Screening of 18 AKXL and 25 AKXD recombinant inbred (RI) strains revealed that all bands in each pattern co-segregated and there were no (0/43) recombinants with Es-26 on mouse Chromosome (Chr) 3. Since CBA/CaJ mice have approximately threefold less sucrase activity than other strains, we intercrossed them with SJL/J mice to map the previously identified SI regulatory gene, Si-r. Fifty-six mice from the F2 generation were assayed for sucrase activity, and the genotype of the murine SI structural gene locus, Si-s, was determined by Southern blot analysis. Nine animals (16%) were homozygous for the CBA/CaJ allele (C) and had an average sucrase activity (jejunum+ileum) of 1.51 mumoles/h/mg protein (SE = 0.067), 19 (34%) were homozygous for the SJL/J allele (S) and had an average sucrase activity of 5.95 mumoles/h/mg protein (SE = 0.267), and 28 (50%) were heterozygous (C/S) for Si-s with an average sucrase activity of 3.70 mumoles/h/mg protein (SE = 0.127). We conclude that Si-s and Si-r are closely linked on Chr 3.

Isolation and Characterization of an Ornithine Aminotransferase-Related Sequence (OATL3) Mapping to 10q26

We used a near full-length human ornithine δ-aminotransferase cDNA, huOAT6, as a probe under low stringency hybridization conditions to identify a new autosomal ornithine δ-aminotransferase-related sequence (OATL3). Cloning and characterization of this sequence reveal it to be a partial nonprocessed pseudogene corresponding to exon 3 and flanking intronic sequences of the ornithine δ-aminotransferase structural gene. Using somatic cell hybrids and fluorescence in situ hybridization, we mapped OATL3 to 10q26, adjacent to the ornithine δ-aminotransferase structural gene locus.