Genetic background of patients from a university medical center in Manhattan: implications for personalized medicine

Background

The rapid progress currently being made in genomic science has created interest in potential clinical applications; however, formal translational research has been limited thus far. Studies of population genetics have demonstrated substantial variation in allele frequencies and haplotype structure at loci of medical relevance and the genetic background of patient cohorts may often be complex.

Methods and Findings

To describe the heterogeneity in an unselected clinical sample we used the Affymetrix 6.0 gene array chip to genotype self-identified European Americans (N = 326), African Americans (N = 324) and Hispanics (N = 327) from the medical practice of Mount Sinai Medical Center in Manhattan, NY. Additional data from US minority groups and Brazil were used for external comparison. Substantial variation in ancestral origin was observed for both African Americans and Hispanics; data from the latter group overlapped with both Mexican Americans and Brazilians in the external data sets. A pooled analysis of the African Americans and Hispanics from NY demonstrated a broad continuum of ancestral origin making classification by race/ethnicity uninformative. Selected loci harboring variants associated with medical traits and drug response confirmed substantial within- and between-group heterogeneity.

Conclusion

As a consequence of these complementary levels of heterogeneity group labels offered no guidance at the individual level. These findings demonstrate the complexity involved in clinical translation of the results from genome-wide association studies and suggest that in the genomic era conventional racial/ethnic labels are of little value.     

Physiological and biochemical effects of Olea europaea leaf extracts from four phenological growth stages on the oogenesis of female locust Locusta migratoria

The effects of olive leaf extract (OLE) are studied on several reproductive variables and the ovarian biochemical composition of Locusta migratoria (Orthoptera: Acrididae) adult females. The methanolic extracts are prepared from the leaves sampled during four phenological growth stages of olive tree: cluster formation (Cf), swelling inflorescence buds (Sib), full flowering (Ff) and endocarp hardening (Eh). When applied to adult females during the pre‐ovipositional phase, the treatment elicites a significant adverse effect on their reproductive potential. Indeed, OLE significantly reduces both fecundity and fertility and affects oocyte growth during the first gonadotrophic cycle, as indicated by measurements of ovarian weight, length of terminal oocytes and ovarian index. Furthermore, OLE is examined with respect to ovarian biochemical components. Biochemical analyses reveal a significant reduction of ovarian contents of proteins, lipids and carbohydrates, suggesting a disruption in the incorporation of the haemolymph metabolites in the oocytes and an interference of OLE with the vitellogenesis process. The antigonadotrophic effect is confirmed by a histological study of the ovaries, which clearly shows a delay in ovarian development and in yolk accumulation in the basal oocytes of treated females. The most effect is noted with the extract prepared from the leaves collected at the swelling inflorescence buds for all measured parameters, which appears to be related to its high content of polyphenols.     

Systemic Regulation of Host Energy and Oogenesis by Microbiome-Derived Mitochondrial Coenzymes

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Oxytocin shapes parental motion during father–infant interaction

An infant-oriented parental repertoire contributes to an infant''s development and well-being. The role of oxytocin (OT) in promoting affiliative bonds and parenting has been established in numerous animal and human studies. Recently, acute administration of OT to a parent was found to enhance the carer''s, but at the same time also the infant''s, physiological and behavioural readiness for dyadic social engagement. Yet, the exact cues that are involved in this affiliative transmission process remain unclear. The existing literature suggests that motion and vocalization are key social signals for the offspring that facilitates social participation, and that distance and motion perception are modulated by OT in humans. Here, we employed a computational method on video vignettes of human parent–infant interaction including 32 fathers that were administered OT or a placebo in a crossover experimental design. Results indicate that OT modulates parental proximity to the infant, as well as the father''s head speed and head acceleration but not the father''s vocalization during dyadic interaction. Similarly, the infant''s OT reactivity is positively correlated with father''s head acceleration. The current findings are the first to report a relationship between the OT system and parental motion characteristics, further suggesting that the cross-generation transmission of parenting in humans might be underlaid by nuanced, infant-oriented, gestures relating to the carer''s proximity, speed and acceleration within the dyadic context.     

Two complementary perspectives on inter-individual genetic distance

This paper examines population structure through the prism of pairwise genetic distances. Two complementary perspectives, framed as two simple questions, are explored: Q1: What is the probability that a random pair of individuals from the same local population is more genetically dissimilar than a random pair from two distinct populations? Q2: On average, how genetically different are two individuals from the same local population, in comparison with two individuals chosen from any two distinct populations? Models are developed to provide quantitative answers for the two questions, given allele frequencies across any number of markers from two diploid populations. The probability from Q1 is shown to drop to zero with increasing number of genetic markers even for very closely-related populations and rare alleles. The average genetic dissimilarity of two individuals from distinct populations diverges from the average dissimilarity of two individuals from the same population by a percentage dependent on estimates of population differentiation. This perspective also suggests a measure of population distance based on the intuitive notion of pairwise genetic distance, along with a simple method of estimation. Results from recent empirical research on inter-individual genetic distance in human populations are analyzed in the context of the theoretical framework.     

Planarian stem cells specify fate yet retain potency during the cell cycle

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