Genetic analysis of candidate genes modifying the age-at-onset in Huntington’s disease

The expansion of a polymorphic CAG repeat in the HD gene encoding huntingtin has been identified as the major cause of Huntington’s disease (HD) and determines 42–73% of the variance in the age-at-onset of the disease. Polymorphisms in huntingtin interacting or associated genes are thought to modify the course of the disease. To identify genetic modifiers influencing the age at disease onset, we searched for polymorphic markers in the GRIK2, TBP, BDNF, HIP1 and ZDHHC17 genes and analysed seven of them by association studies in 980 independent European HD patients. Screening for unknown sequence variations we found besides several silent variations three polymorphisms in the ZDHHC17 gene. These and polymorphisms in the GRIK2, TBP and BDNF genes were analysed with respect to their association with the HD age-at-onset. Although some of the factors have been defined as genetic modifier factors in previous studies, none of the genes encoding GRIK2, TBP, BDNF and ZDHHC17 could be identified as a genetic modifier for HD.Electronic Supplementary Material Supplementary material is available to authorised users in the online version of this article at .     

Transcriptome analysis of differentially expressed genes in rabbits’ ovaries by digital gene-expression profiling

Reproduction is a complex physiological process that is regulated by multiple genes and pathways. Compared with studies of common livestock, fewer studies of genes related to the fertility of rabbits (Oryctolagus cuniculus) have been reported, and the molecular mechanism of their high productivity is still poorly understood. To identify candidate genes associated with development and prolificacy in rabbits, we analyzed gene expression differences among the ovaries of mature Californian rabbit (LC), and mature (HH) and immature Harbin white rabbit (IH) using digital gene expression technology. We detected 885 and 321 genes that were significantly differentially expressed in comparisons between HH/IH and HH/LC, respectively. The functions of the differentially expressed genes (DEGs) were determined by GO classification and KEGG pathway analysis. The results suggest that most of the DEGs between the mature and immature developmental stages were predominantly associated with DNA replication, cell cycle, and progesterone-mediated oocyte maturation, and most were up-regulated in the IH group compared with the HH group. The DEGs involved in disparate fecundities between HH and LC were associated with reproduction, fructose and mannose metabolism, steroid hormone biosynthesis, and pyruvate metabolism. Our results will contribute to a better understanding of changes in the regulatory network in ovary at different developmental stages and in different fertility of rabbit.     

Characterization of the flanking regions of the S-RNase genes of Japanese pear (Pyrus serotina) and apple (Malus×domestica)

Genomic sequences of the self-incompatibility genes, the S-RNase genes, from two rosaceous species, Japanese pear and apple, were characterized. Genomic Southern blot and sequencing of a 4.5-kb genomic clone showed that the S⁴-RNase gene of Japanese pear is surrounded by repetitive sequences as in the case of the S-RNase genes of solanaceous species. The flanking regions of the S²- and S^f-RNase genes of apple were also cloned and sequenced. The 5′ flanking regions of the three alleles bore no similarity with those of the solanaceous S-RNase genes, although the position and sequence of the putative TATA box were conserved. The putative promoter regions of the Japanese pear S⁴- and apple S^f-RNase genes shared a stretch of about 200 bp with 80% sequence identity. However, this sequence was not present in the S²-RNase gene of apple, and thus it may reflect a close relationship between the S⁴- and S^f-RNase genes rather than a cis-element important in regulating gene expression. Despite the uniform pattern of expression of the rosaceous S-RNase genes, sequence motifs conserved in the 5′ flanking regions of the three alleles were not found, implying that the cis-element controlling pistil specific gene expression also locates at the intragenic region or upstream of the analyzed promoter region.     

Species composition and abundance of earthworms in the tundra biocenoses of Denezhkin Kamen’ Mountain (Northern Urals)

Taxonomic composition of earthworms was analyzed and their abundance in the tundra belt of Denezhkin Kamen’ Mt. in the Northern Urals was estimated. Four species were revealed: Perelia diplotetratheca (Perel, 1976), Eisenia nordenskioldi (Eisen, 1879), E. atlavinyteae Perel et Graphodatsky, 1984 and Dendrobaena octaedra (Savigny, 1826). It was shown that earthworms dominate in biomass over other groups of soil mesofauna under the mountainous conditions.     

Distribution, abundance, and utilization of wild berries by the gwich’in people in the Mackenzie River Delta region

This paper examines the abundance and Aboriginal use of botanical non-timber forest products in the Gwich’in Settlement Area in the Northwest Territories, Canada. Informants indicated that wild berries are important to Gwich’in diets and an important factor in culture and traditional land use. People collected mostly cloudberries (Rubus chamaemorus), blueberries (Vaccinium uliginosum), and lingonberries (Vaccinium vitisidaea). The total quantities collected were estimated to be greater than other published accounts of berry gathering by northern Aboriginal peoples in North America. The total collected by the 450 households in the year 2000 was about 16,000 L. Inventories of wild berries on the landscape suggest that substantial quantities could be collected for commercial production, although the between-year supply can show considerable variation.     

TNFα enhances the motility and invasiveness of prostatic cancer cells by stimulating the expression of selective glycosyl- and sulfotransferase genes involved in the synthesis of selectin ligands

Sialyl Lewis x (sLe^x) plays an important role in cancer metastasis. But, the mechanism for its production in metastatic cancers remains unclear. The objective of current study was to examine the effects of a proinflammatory cytokine on the expression of glycosyltransferase and sulfotransferase genes involved in the synthesis of selectin ligands in a prostate cancer cell line. Androgen-independent human lymph node-derived metastatic prostate cancer cells (C-81 LNCaP), which express functional androgen receptor and mimic the castration-resistant advanced prostate cancer, were used. TNFα treatment of these cells increased their binding to P-, E- and L-selectins, anti-sLe^x antibody, and anti-6-sulfo-sialyl Lewis x antibody by 12%, 240%, 43%, 248% and 21%, respectively. Also, the expression of C2GnT-1, B4GalT1, GlcNAc6ST3, and ST3Gal3 genes was significantly upregulated. Further treatment of TNFα-treated cells with either anti-sLe^x antibody or E-selectin significantly suppressed their in vitro migration (81% and 52%, respectively) and invasion (45% and 56%, respectively). Our data indicate that TNFα treatment enhances the motility and invasion properties of LNCaP C-81 cells by increasing the formation of selectin ligands through stimulation of the expression of selective glycosyl- and sulfotransferase genes. These results support the hypothesis that inflammation contributes to cancer metastasis.     

Ancestors’ dietary patterns and environments could drive positive selection in genes involved in micronutrient metabolism—the case of cofactor transporters

Background

During evolution, humans colonized different ecological niches and adopted a variety of subsistence strategies that gave rise to diverse selective pressures acting across the genome. Environmentally induced selection of vitamin, mineral, or other cofactor transporters could influence micronutrient-requiring molecular reactions and contribute to inter-individual variability in response to foods and nutritional interventions.

Methods

A comprehensive list of genes coding for transporters of cofactors or their precursors was built using data mining procedures from the HGDP dataset and then explored to detect evidence of positive genetic selection. This dataset was chosen since it comprises several genetically diverse worldwide populations whom ancestries have evolved in different environments and thus lived following various nutritional habits and lifestyles.

Results

We identified 312 cofactor transporter (CT) genes involved in between-cell or sub-cellular compartment distribution of 28 cofactors derived from dietary intake. Twenty-four SNPs distributed across 14 CT genes separated populations into continental and intra-continental groups such as African hunter-gatherers and farmers, and between Native American sub-populations. Notably, four SNPs were located in SLC24A3 with one being a known eQTL of the NCKX3 protein.

Conclusions

These findings could support the importance of considering individual’s genetic makeup along with their metabolic profile when tailoring personalized dietary interventions for optimizing health.

     

Behavior and seasonal variation in the relative abundance of Commerson’s dolphin (Cephalorhynchus commersonii) in northern Patagonia, Argentina

Commerson’s dolphins (Cephalorhynchus commersonii) along the Patagonian coast of South America suffer incidental mortality in fisheries and are the target of a dolphin-watching industry. We describe the daily activity patterns and assess the variation in the relative abundance of the species near the northern boundary of its range. Information was gathered with a spotting scope from a cliff-top vantage point applying the method of scan sampling. Behaviors were categorized as individual feeding, cooperative feeding, directional swimming, socializing, and resting. These behaviors are similar to those observed in other species of small cetacean, but differences were found regarding the patterns of directional swimming and feeding techniques. Hunting tactics favored the association of terns with dolphin groups. No clear dial behavioral pattern was observed, but seasonal changes in the frequency of behaviors were recorded. Group and school sizes were larger during periods with colder sea surface temperature (SST). Seasonal abundance was correlated with SST, suggesting that at higher SST the species forsakes the area, probably in favor of coastal areas to the south with lower SST.     

Distribution and seasonal changes in fish abundance in the estuary of the Razdol’naya River (Peter the Great Bay), Sea of Japan

The distribution and seasonal dynamics of fish abundance in the estuary of the Razdol’naya River (Peter the Great Bay) depending on several abiotic factors are considered. It is established that fish biomass increases with an increase in salinity and decrease in water temperature (both in space and time). Freshwater stenohaline species dominate in the upper part of the estuary, semianadromous and freshwater euryhaline species dominate in the middle part, and semianadromous and marine species dominate in the lower part. The seasonal succession of ichthyocenosis includes two periods: warm (May–October) and cold (November–April). The warm period is characterized by a low biomass (4–10 g/m²) and maximum species richness (22–29 species) against the background of a decrease of the penetration into the estuary of high-saline waters and an increase in the water discharge, turbidity, and temperature. Freshwater species dominate in catches, and subtropical migrants appear. In the cold period, species richness is minimal (2–12 species), and biomass is, on the contrary, very high (on average, 71–374 g/m²); water temperature and discharge are minimal. In catches, the proportion of semianadromous and marine species is maximum.     

Sequence comparison of the 5’ flanking regions of Japanese pear (Pyrus pyrifolia) S-RNases associated with gametophytic self-incompatibility

Genomic clones of 2.8 kb, 4.3 kb and 6.5 kb for the S₂-, S₃- and S₅-RNases of Japanese pear(Pyrus pyrifolia), respectively, were isolated and sequenced. Comparison of the 5’-flanking regions of these genes with the same region of the S₄-RNase gene indicated that a highly similar region of approximately 200 bp exists in the regions just upstream of the putative TATA boxes of the four Japanese pear S-RNase genes. This suggests the presence of cis-regulatory element(s) in this region. Received: 5 October 2000 / Revision accepted: 2 January 2001