Genome-wide linkage analysis of age at onset of alcohol dependence: a comparison between microsatellites and single-nucleotide polymorphisms

Background

Using the dataset provided for Genetic Analysis Workshop 14 by the Collaborative Study on the Genetics of Alcoholism, we performed genome-wide linkage analysis of age at onset of alcoholism to compare the utility of microsatellites and single-nucleotide polymorphisms (SNPs) in genetic linkage study.

Methods

A multipoint nonparametric variance component linkage analysis method was applied to the survival distribution function obtained from semiparametric proportional hazards model of the age at onset phenotype of alcoholism. Three separate linkage analyses were carried out using 315 microsatellites, 2,467 and 9,467 SNPs, spanning the 22 autosomal chromosomes.

Results

Heritability of age at onset was estimated to be approximately 12% (p < 0.001). We observed weak correlation, both in trend and strength, of genome-wide linkage signals between microsatellites and SNPs. Results from SNPs revealed more and stronger linkage signals across the genome compared with those from microsatellites. The only suggestive evidence of linkage from microsatellites was on chromosome 1 (LOD of 1.43). Differences in map densities between the two sets of SNPs used in this study did not appear to confer an advantage in terms of strength of linkage signals.

Conclusion

Our study provided support for better performance of dense SNP maps compared with the sparse mirosatellite maps currently available for linkage analysis of quantitative traits. This better performance could be attributable to precise definition and high map resolutions achievable with dense SNP maps, thus resulting in increased power to detect possible loci affecting given trait or disease.

     

Correlations between capillary microscopy and electrocardiographic results in the diabetic

Ninety-nine diabetics were simultaneously given a capillaroscopic examination of periungual walls and an electrocardiogram evaluated according to the Minnesota Code. From these tests the following data were recorded: a. the number of knobs revealed by capillaroscopy is inferior, in a statistically significant manner, in groups having "major abnormalities"; b. capillaroscopic abnormalities did not seem to be definitely correlated to age, but rather to the length of time diabetes mellitus was present; in particular, these abnormalities were quite evident in subjects diagnosed as diabetics for the first time. This procedure is therefore extremely useful for the early diagnosis of diabetic microangiopathy; c. electrocardiographic abnormalities are correlated to patient's age, whereas are not related to the period of the illness. Although the small sampling obliges us to maintain certain reservations, such abnormalities were more frequent in subjects taking antidiabetic drugs orally.     

Conceptual translation of timeless reveals alternative initiating methionines in Drosophila.

We have sequenced genomic fragments which encode the N-terminus of the TIMELESS (TIM) clock protein in Drosophila simulans and D. yakuba. We observe that in these two species, the initiating methionine appears to lie downstream of the one proposed to encode the translational start inD.melanogaster, thereby truncating the N-terminus by 23 amino acids. We then sequenced the corresponding 5'fragment in a number of D. melanogaster individuals from different strains. We observed a polymorphism which strongly suggests that the originally proposed start site cannot be utilised in some individuals, and that these flies will initiate translation of TIM at the downstream ATG. Given the current interest in TIM regulation in D. melanogaster, it is important to correctly define the N-terminus in this species.     

The contribution of pleiotropy to blood pressure and body-mass index variation: the Gubbio Study.

Blood pressure (BP), body-mass index (BMI), and quantitative phenotypes thought to influence BP (e.g., lithium-sodium countertransport activity) were studied in 2,184 households comprising 5,376 people in Gubbio, Italy. Variance-components models were used to partition the variation of these phenotypes into components characterizing the effects of age-related, measured environmental, additive genetic, pleiotropic, unmeasured shared-household, and individual-specific (or random) factors. The goal of the investigation was to estimate the contribution of pleiotropy to variation in BP and BMI in population-based samples. Although our results suggest that numerous significant bivariate genetic correlations exist between BP and some of the traits investigated, they ultimately lead us to reject a prominent role for any individual bivariate pleiotropic system influencing the natural variation of BP. However, because we found evidence that many traits enter into small-impact pleiotropic relationships with BP, we cannot rule out the possibility that pleiotropic genes, when considered collectively, may contribute to BP variation at the population level. Similar results were obtained when BMI was taken as the primary variable of interest. We argue that the small but significant portion of BP variation explained by individual genes displaying bivariate pleiotropic effects is intuitive, in light of the relatively low heritabilities associated with quantitative cardiovascular phenotypes and the low phenotypic correlations between BP, BMI, and many other physiologically linked measures of cardiovascular function. Our results not only bear directly on both the nature of the multifactorial determinants of BP and the maintenance of BP variation in the population at large, but also emphasize the utility of variance-components models in epidemiologic and population genetics research. We discuss the implications of our results for genetic epidemiologists and medical researchers studying hypertension, as well as the limitations of our study and areas for future research.     

Prioritizing regionally rare plant species for conservation using herbarium data

Because the conservation of biodiversity occurs under time and resource constraints, it is necessary to prioritize species most deserving of attention. Natural history collections have been identified as a valuable source of information in applied conservation practice, particularly for species-rich taxa like plants. Here, online herbarium information was combined with a novel, straightforward priority setting approach to screen a large list of rare vascular plant species (n = 418) in Saskatchewan, Canada. Data was quantified to develop priority scores (for a given species) using three key criteria: (1) provincial responsibility in species survival, (2) species local population characteristics, and (3) the anthropogenic threats causing species to be rare. The use of a hierarchy of the three criteria, wherein provincial responsibility was assigned the most weight, resulted in the highest ranking for 13 species that exist only in Saskatchewan and no other Canadian province or territory. The list is a first step in identifying species deserving of conservation attention and/or further study, while the method itself was deemed to be highly relevant to conservation managers and decision makers due to its scale adaptability and fairly minimal resource requirements.     

Trypanosoma evansi: Hematologic changes in experimentally infected cats

This study aimed at evaluating hemogram and erythropoietic changes in cats experimentally infected with Trypanosoma evansi. Thirteen adult female non-breeding Felix catus were separated into two groups: seven animals were infected with 10⁸ trypomastigotes each, and six animals were used as negative controls. Animals were kept in air-conditioned rooms and blood smears were performed daily for 49 days. Blood samples were collected from the jugular vein at days 0, 7, 21, 35 and 49 and stored in blood-collecting tubes containing anticoagulant. Bone marrow was collected from the proximal epiphysis of the right femur at days 14 and 42 post-inoculation (PI). Total erythrocyte count, hematocrit and hemoglobin showed statistical differences among groups from the seventh day PI onwards (P < 0.05). The mean corpuscular volume and the mean corpuscular hemoglobin concentration remained normal, characterizing a normocytic-normochromic anemia. Reticulocyte count increased in the infected group from the 21st day onwards, but remained near normal values suggesting a mild regenerative anemia. Moreover, the myeloid:erythroid ratio significantly reduced at day 42 PI, evidencing a bone marrow hematopoietic response. Based on these results we conclude that cats infected with T. evansi have normocytic, normochromic, regenerative anemia.     

Interactions fulvate-metal (Zn<Superscript>2+</Superscript>, Cu<Superscript>2+</Superscript> and Fe<Superscript>2+</Superscript>): theoretical investigation of thermodynamic,structural and spectroscopic properties

The use of theoretical calculation to determine structural properties of fulvate-metal complex (zinc, copper and iron) is here related. The species were proposed in the ratio 1:1 and 2:1 for which the molecular structure was obtained through the semi-empirical method PM6. The calculation of thermodynamic stability (\(\Delta H_{(aq.)}^{0}\)) predicted that the iron complex were more exo-energetic. Metallic ions were coordinated to the phtalate groups of the model-structure of fulvic acid Suwannee River and the calculations of vibrational frequencies suggested that hydrogen bonds may help on the stability of the complex formation.