Estimation of heterozygosity for single-probe multilocus DNA fingerprints

In spite of the increasing application of DNA fingerprinting to natural populations and to the genetic identification of humans, explicit methods for estimation of basic population genetic parameters from DNA fingerprinting data have not been developed. Contributing to this omission is the inability to determine, for multilocus fingerprinting probes, relatively important genetic information, such as the number of loci, the number of alleles, and the distribution of these alleles into specific loci. One of the most useful genetic parameters that could be derived from such data would be the average heterozygosity, which has traditionally been employed to measure the level of genetic variation within populations and to compare genetic variation among different loci. We derive here explicit formulas for both the estimation of average heterozygosity at multiple hypervariable loci and a maximum value for this estimate. These estimates are based upon the DNA restriction-pattern matrices that are typical for fingerprinting studies of humans and natural populations. For several empirical data sets from our laboratory, estimates of average and maximal heterozygosity are shown to be relatively close to each other. Furthermore, variances of these statistics based on simulation studies are relatively small. These observations, as well as consideration of the effect of missing alleles and alternate numbers of loci, suggest that the average heterozygosity can be accurately estimated using phenotypic DNA fingerprint patterns, because this parameter is relatively insensitive to the lack of certain genetic information.      

Effects of Holocene climate change on the historical demography of migrating sharp-shinned hawks (Accipiter striatus velox) in North America

DNA sequences of the mitochondrial control region were analysed from 298 individual sharp-shinned hawks (Accipiter striatus velox) sampled at 12 different migration study sites across North America. The control region proved to be an appropriate genetic marker for identification of continental-scale population genetic structure and for determining the historical demography of population units. These data suggest that sharp-shinned hawks sampled at migration sites in North America are divided into distinct eastern and western groups. The eastern group appears to have recently expanded in response to the retreat of glacial ice at the end of the last glacial maximum. The western group appears to have been strongly effected by the Holocene Hypsithermal dry period, with molecular evidence indicating the most recent expansion following this mid-Holocene climatic event 7000-5000 years before present.     

Patterns of population subdivision, gene flow and genetic variability in the African wild dog (Lycaon pictus)

African wild dogs are large, highly mobile carnivores that are known to disperse over considerable distances and are rare throughout much of their geographical range. Consequently, genetic variation within and differentiation between geographically separated populations is predicted to be minimal. We determined the genetic diversity of mitochondrial DNA (mtDNA) control region sequences and microsatellite loci in seven populations of African wild dogs. Analysis of mtDNA nucleotide diversity suggests that, historically, wild dog populations have been small relative to other large carnivores. However, population declines due to recent habitat loss have not caused a dramatic reduction in genetic diversity. We found one historical and eight recent mtDNA genotypes in 280 individuals that defined two highly divergent clades. In contrast to a previous, more limited, mtDNA analysis, sequences from these clades are not geographically restricted to eastern or southern African populations. Rather, we found a large admixture zone spanning populations from Botswana, Zimbabwe and south-eastern Tanzania. Mitochondrial and microsatellite differentiation between populations was significant and unique mtDNA genotypes and alleles characterized the populations. However, gene flow estimates (Nm) based on microsatellite data were generally greater than one migrant per generation. In contrast, gene flow estimates based on the mtDNA control region were lower than expected given differences in the mode of inheritance of mitochondrial and nuclear markers which suggests a male bias in long-distance dispersal.     

Experimental evaluation of the relationship between lethal or non-lethal virulence and transmission success in malaria parasite infections

Background

Theoretical studies suggest that direct and indirect selection have the potential to cause substantial evolutionary change in female mate choice. Similarly, sexual selection is considered a strong force in the evolution of male attractiveness and the exaggeration of secondary sexual traits. Few studies have, however, directly tested how female mate choice and male attractiveness respond to selection. Here we report the results of a selection experiment in which we selected directly on female mating preference for attractive males and, independently, on male attractiveness in the guppy, Poecilia reticulata. We measured the direct and correlated responses of female mate choice and male attractiveness to selection and the correlated responses of male ornamental traits, female fecundity and adult male and female survival.

Results

Surprisingly, neither female mate choice nor male attractiveness responded significantly to direct or to indirect selection. Fecundity did differ significantly among lines in a way that suggests a possible sexually-antagonistic cost to male attractiveness.

Conclusions

The opportunity for evolutionary change in female mate choice and male attractiveness may be much smaller than predicted by current theory, and may thus have important consequences for how we understand the evolution of female mate choice and male attractiveness. We discuss a number of factors that may have constrained the response of female choice and male attractiveness to selection, including low heritabilities, low levels of genetic (co)variation in the multivariate direction of selection, sexually-antagonistic constraint on sexual selection and the "environmental covariance hypothesis".

     

Trends and Determinants of Oral Anti-Diabetic Initiation in Youth with Suspected Type 2 Diabetes

Objective

To evaluate trends and identify predictors of treatment initiation of oral anti-diabetic drugs (OAD) in youth.

Patients and Methods

We identified a select population of children, ages 8–18 years, with at least 13 months of continuous health plan coverage within the years 2001–2012 in a large US commercial insurance claims database. New use of an OAD was defined as the first claim for an outpatient dispensing following a 12-month wash out period. Treatment incidence was estimated monthly over the study period, and stratified by age, gender, geographic region, and provider specialty.

Results

The median size of the source population during the study period was 2.2 million children. A total of 13,824 initiators (mean monthly incidence of 4.6 (95% CI = 3.6, 5.5) per 100,000 youths) were identified. Initiators were more likely to be females, age 15–18, from the southern region, and have visited a family practitioner (versus a general pediatrician) prior to initiation. Time trends demonstrate a 43% increase in initiation from 2002–2012, with a gradual decrease starting from early 2008.

Conclusion

Incidence of filled OAD medications in youth increased over time, especially for patients treated by family practitioners. Additional research is needed into factors influencing prescribing by family practitioners and pediatricians.     

Haptoglobin and CCR2 receptor expression in ovarian cancer cells that were exposed to ascitic fluid: Exploring a new role of haptoglobin in the tumoral microenvironment

Haptoglobin (Hp) is an acute-phase protein that is produced by the liver to capture the iron that is present in the blood circulation, thus avoiding its accumulation in the blood. Moreover, Hp has been detected in a wide variety of tissues, in which it performs various functions. In addition, this protein is considered a potential biomarker in many diseases, such as cancer, including ovarian carcinoma; however, its participation in the cancerous processes has not yet been determined. The objective of this work was to demonstrate the expression of Hp and its receptor CCR2 in the ovarian cancer cells and its possible involvement in the process of cell migration through changes in the rearrangement of the actin cytoskeleton using western blot and wound-healing assays and confirming by confocal microscopy. Ovarian cancer cells express both Hp and its receptor CCR2 but only after exposure to ascitic fluid, inducing moderated cell migration. However, when the cells are exposed to exogenous Hp, the expression of CCR2 is induced together with drastic changes in the actin cytoskeleton rearrangement. At the same time, Hp induced cell migration in a much more efficient manner than did ascitic fluid. These effects were blocked when the CCR2 synthetic antagonist RS102895 was used to pretreat the cells. These results suggest that Hp-induced changes in the cell morphology, actin cytoskeleton structure, and migration ability of tumor cells, is possibly “preparing” these cells for the potential induction of the metastatic phenotype.