Molecular scanning of the human PPARa gene: association of the L162v mutation with hyperapobetalipoproteinemia

Peroxisome proliferator-activated receptor alpha (PPARalpha) is a member of the steroid hormone receptor super family involved in the control of cellular lipid utilization. This makes PPARalpha a candidate gene for type 2 diabetes and dyslipidemia. The aim of this study was to investigate whether genetic variation in the human PPARalpha gene can influence the risk of type 2 diabetes and dyslipidemia among French Canadians. We therefore first determined the genomic structure of human PPARalpha, and then designed intronic primers to sequence the coding region and the exon-intron boundaries of the gene in 12 patients with type 2 diabetes and in 2 nondiabetic subjects. Sequence analysis revealed the presence of a L162V missense mutation in exon 5 of one diabetic patient. Leucine 162 is contained within the DNA binding domain of the human PPARalpha gene, and is conserved among humans, mice, rats, and guinea pigs. We subsequently screened a sample of 121 patients newly diagnosed with type 2 diabetes and their age and sex-matched nondiabetic controls, recruited from the Saguenay-Lac-St-Jean region of Northeastern Quebec, for the presence of the L162V mutation by a PCR-RFLP based method. There was no difference in L162 homozygote or V162 carrier frequencies between diabetics and nondiabetics. However, whether diabetic or not, carriers of the V162 allele had higher plasma apolipoprotein B levels compared to noncarriers (P 5 0.05). To further this association, we screened another sample of 193 nondiabetic subjects recruited in the greater Quebec City area. Carriers of the V162 allele compared with homozygotes of the L162 allele had significantly higher concentrations of plasma total and LDL-apolipoprotein B as well as LDL cholesterol (P 相似文献   

MATE CHOICE BASED UPON NATURALLY OCCURRING COLOR-PATTERN VARIATION IN A GUPPY POPULATION

This study tested the effect of differences in the extent of orange pigment in the color pattern of male guppies on the sexual responsiveness of females. Fish used in this study were descendants of a single natural population from the Paria River of Trinidad. Males from this population have unusually large, brilliant orange spots. I used three experimental approaches to test for discrimination by females among males based on the relative area of orange in color patterns: 1) the time to mating when a male was presented to a virgin female; 2) the frequency of sexual responses of females to passing, nondisplaying males; and 3) the proportion of a male's courtship displays that elicited a female sexual response. In all three experiments, females appeared to discriminate against males with less-than-average amounts of orange in their color patterns. In at least one experiment, however, the increase in female responsiveness with increasing amounts of orange leveled off and possibly decreased at high levels of orangeness. This suggests that there may be no advantage of increased amounts of orange above a certain level. These results suggest that female choice is a mechanism for the evolution of color patterns in guppies and may have contributed to the distinctive color pattern of the Paria population.     

Molecular and genealogical characterization of the R1443X BRCA1 mutation in high-risk French-Canadian breast/ovarian cancer families

The Quebec population contains about six-million French Canadians, descended from the French settlers who colonized Nouvelle-France between 1608 and 1765. Although the relative genetic contribution of each of these founders is highly variable, altogether they account for the major part of the contemporary French-Canadian gene pool. This study was designed to analyze the role of this founder effect in the introduction and diffusion of the BRCA1 recurrent R1443X mutant allele. A highly conserved haplotype, observed in 18 French-Canadian families and generated using 17 microsatellite markers surrounding the BRCA1 locus, supports the fact that the R1443X mutation is a founder mutation in the Quebec population. We also performed haplotyping analysis of R1443X carriers on 19 other families from seven different nationalities; although the same alleles are shared for three markers surrounding the BRCA1 gene, distinct haplotypes were obtained in four families, suggesting multiple origins for the R1443X mutation. Ascending genealogies of the 18 French Canadian families and of controls were reconstructed on an average depth of 10 generations. We identified the founder couple with the highest probability of having introduced the mutation in the population. Based on the descending genealogy of this couple, we detected the presence of geographical concentration in the diffusion pattern of the mutation. This study demonstrates how molecular genetics and demogenetic analyses can complement each other to provide findings that could have an impact on public health. Moreover, this approach is certainly not unique to breast cancer genetics and could be used to understand other complex traits.Other members of the BCLC Haplotype Group involved in this study are listed in Appendix 1Other members of INHERIT BRCAs involved in this study are listed in Appendix 2H. Vézina and F. Durocher contributed equally to this work and should be regarded as joint first author     

Leishmania donovani lipophosphoglycan disrupts phagosome microdomains in J774 macrophages

Clearance of pathogens by phagocytosis and their killing in phagolysosomes is a key aspect of our innate ability to fight infectious agents. Leishmania parasites have evolved ways to survive and replicate in macrophages by inhibiting phagosome maturation and avoiding the harsh environment of phagolysosomes. We describe here that during this process Leishmania donovani uses a novel strategy involving its surface lipophosphoglycan (LPG), a virulence factor impeding many host functions, to prevent the formation or disrupt lipid microdomains on the phagosome membrane. LPG acts locally on the membrane and requires its repetitive carbohydrate moieties to alter the organization of microdomains. Targeting and disruption of functional foci, where proteins involved in key aspects of phagolysosome biogenesis assemble, is likely to confer a survival advantage to the parasite.     

Overexpression of the acidic dehydrin WCOR410 improves freezing tolerance in transgenic strawberry leaves

Progress in freezing tolerance (FT) improvement through plant breeding approaches has met with little success in the last 50 years. Engineering plants for greater FT through plant transformation is one possible way to reduce the damage caused by freezing. Here, we report an improvement of the selection procedure and the transfer of the wheat Wcor410a acidic dehydrin gene in strawberry. The encoded protein has previously been shown to be associated with the plasma membrane, and its level of accumulation has been correlated with the degree of FT in different wheat genotypes. The WCOR410 protein was expressed in transgenic strawberry at a level comparable with that in cold-acclimated wheat. Freezing tests showed that cold-acclimated transgenic strawberry leaves had a 5 degrees C improvement of FT over wild-type or transformed leaves not expressing the WCOR410 protein. However, no difference in FT was found between the different plants under non-acclimated conditions, suggesting that the WCOR410 protein needs to be activated by another factor induced during cold acclimation. These data demonstrate that the WCOR410 protein prevents membrane injury and greatly improves FT in leaves of transgenic strawberry. A better understanding of the limiting factors allowing its activation may open up the way for engineering FT in different plant organs, and may find applications for the cryopreservation of human tissues and organs.     

GEOGRAPHIC VARIATION IN FEMALE PREFERENCES FOR MALE TRAITS IN POECILIA RETICULATA

We examined the preferences of female guppies (Poecilia reticulata) from 11 localities in Trinidad with respect to male color-pattern elements, body shape and size, and overall color and brightness contrast. Females are on average more attracted to males from their own population than from alien populations, and populations appear to vary in the criteria used in female choice. Multiple-regression analysis suggests that mate-preference criteria vary among localities in intensity, sign, and the number of traits used. Although preference estimators and color-pattern parameters are unique to each population, only orange, black, and color contrast showed a correlation between degree of male trait and degree of preference for that trait. There is a clear effect of water color and a possible effect of predation intensity. The results are discussed in light of various models of sexual selection and the early stages of speciation.     

An integrative approach to identify hexaploid wheat miRNAome associated with development and tolerance to abiotic stress

Background

Wheat is a major staple crop with broad adaptability to a wide range of environmental conditions. This adaptability involves several stress and developmentally responsive genes, in which microRNAs (miRNAs) have emerged as important regulatory factors. However, the currently used approaches to identify miRNAs in this polyploid complex system focus on conserved and highly expressed miRNAs avoiding regularly those that are often lineage-specific, condition-specific, or appeared recently in evolution. In addition, many environmental and biological factors affecting miRNA expression were not yet considered, resulting still in an incomplete repertoire of wheat miRNAs.

Results

We developed a conservation-independent technique based on an integrative approach that combines machine learning, bioinformatic tools, biological insights of known miRNA expression profiles and universal criteria of plant miRNAs to identify miRNAs with more confidence. The developed pipeline can potentially identify novel wheat miRNAs that share features common to several species or that are species specific or clade specific. It allowed the discovery of 199 miRNA candidates associated with different abiotic stresses and development stages. We also highlight from the raw data 267 miRNAs conserved with 43 miRBase families. The predicted miRNAs are highly associated with abiotic stress responses, tolerance and development. GO enrichment analysis showed that they may play biological and physiological roles associated with cold, salt and aluminum (Al) through auxin signaling pathways, regulation of gene expression, ubiquitination, transport, carbohydrates, gibberellins, lipid, glutathione and secondary metabolism, photosynthesis, as well as floral transition and flowering.

Conclusion

This approach provides a broad repertoire of hexaploid wheat miRNAs associated with abiotic stress responses, tolerance and development. These valuable resources of expressed wheat miRNAs will help in elucidating the regulatory mechanisms involved in freezing and Al responses and tolerance mechanisms as well as for development and flowering. In the long term, it may help in breeding stress tolerant plants.

Electronic supplementary material

The online version of this article (doi:10.1186/s12864-015-1490-8) contains supplementary material, which is available to authorized users.     

Admixed ancestry and stratification of Quebec regional populations

Population stratification results from unequal, nonrandom genetic contribution of ancestors and should be reflected in the underlying genealogies. In Quebec, the distribution of Mendelian diseases points to local founder effects suggesting stratification of the contemporary French Canadian gene pool. Here we characterize the population structure through the analysis of the genetic contribution of 7,798 immigrant founders identified in the genealogies of 2,221 subjects partitioned in eight regions. In all but one region, about 90% of gene pools were contributed by early French founders. In the eastern region where this contribution was 76%, we observed higher contributions of Acadians, British and American Loyalists. To detect population stratification from genealogical data, we propose an approach based on principal component analysis (PCA) of immigrant founders' genetic contributions. This analysis was compared with a multidimensional scaling of pairwise kinship coefficients. Both methods showed evidence of a distinct identity of the northeastern and eastern regions and stratification of the regional populations correlated with geographical location along the St-Lawrence River. In addition, we observed a West-East decreasing gradient of diversity. Analysis of PC-correlated founders illustrates the differential impact of early versus latter founders consistent with specific regional genetic patterns. These results highlight the importance of considering the geographic origin of samples in the design of genetic epidemiology studies conducted in Quebec. Moreover, our results demonstrate that the study of deep ascending genealogies can accurately reveal population structure.     

Oxidation of 4-methylcatechol: implications for the oxidation of catecholamines

At alkaline pH, 4-methylcatechol oxidizes more rapidly than the related catecholamines: dopamine, norepinephrine, and epinephrine. This oxidation is not inhibited by superoxide dismutase or catalase, indicating that O2 itself is the oxidant, but the reduction potential of O2/O2-* is too low for it to oxidize 4-methylcatechol directly. Instead, O2 oxidizes the 4-methylcatechol semiquinone, which is formed by comproportionation of 4-methylcatechol and its o-quinone. Aniline reacts very quickly with the o-quinone and thus stops the comproportionation reaction that oxidizes 4-methylcatechol to the semiquinone. Oxidation of 4-methylcatechol then requires superoxide, and in the presence of aniline, oxidation of 4-methylcatechol by O2 is inhibited by superoxide dismutase. When catecholamines oxidize, the side chain amine inserts into the catechol o-quinone, forming a bicyclic compound. By eliminating the quinone, this ring closure prevents comproportionation and the consequent oxidation of catecholamines by O2. It also prevents reaction of the quinone with other compounds and the formation of potentially toxic products.