LINE-1 Retrotransposition Assays in Embryonic Stem Cells.

The ongoing mobilization of active non-long terminal repeat (LTR) retrotransposons continues to impact the genomes of most mammals, including humans and rodents. Non-LTR retrotransposons mobilize using an intermediary RNA and a copy-and-paste mechanism termed retrotransposition. Non-LTR retrotransposons are subdivided into long and short interspersed elements (LINEs and SINEs, respectively), depending on their size and autonomy; while active class 1 LINEs (LINE-1s or L1s) encode the enzymatic machinery required to mobilize in cis, active SINEs use the enzymatic machinery of active LINE-1s to mobilize in trans. The mobilization mechanism used by LINE-1s/SINEs was exploited to develop ingenious plasmid-based retrotransposition assays in cultured cells, which typically exploit a reporter gene that can only be activated after a round of retrotransposition. Retrotransposition assays, in cis or in trans, are instrumental tools to study the biology of mammalian LINE-1s and SINEs. In fact, these and other biochemical/genetic assays were used to uncover that endogenous mammalian LINE-1s/SINEs naturally retrotranspose during early embryonic development. However, embryonic stem cells (ESCs) are typically used as a cellular model in these and other studies interrogating LINE-1/SINE expression/regulation during early embryogenesis. Thus, human and mouse ESCs represent an excellent model to understand how active retrotransposons are regulated and how their activity impacts the germline. Here, we describe robust and quantitative protocols to study human/mouse LINE-1 (in cis) and SINE (in trans) retrotransposition using (human and mice) ESCs. These protocols are designed to study the mobilization of active non-LTR retrotransposons in a cellular physiologically relevant context.

BDNF Val66Met is Associated With Performance in a Computerized Visual-Motor Tracking Test In Healthy Adults.

The brain-derived neurotrophic factor gene (BDNF) is known to play an important role in neuroplasticity and cognitive processes. We explored the association of BDNF Val66Met polymorphism with performance in a visual-motor tracking test. One hundred and sixty-seven young, healthy Colombian adults completed a computerized version of the Pursuit Rotor Task, using the Psychology Experiment Building Language (PEBL) platform. DNA genotyping was performed by allele-specific polymerase chain reaction. We found that BDNF Val/Met and Met/Met subjects performed better in the pursuit rotor task (p = .03). Our findings suggest that the BDNF gene is essential to understand differences in motor performance in healthy participants in different populations. This approach could be useful for future fine mapping of genetic modifiers for neuropsychiatric diseases.

Functional polymorphisms in BDNF and COMT genes are associated with objective differences in arithmetical functioning in a sample of young adults.

BACKGROUND: Understanding the molecular genetics of complex human behaviors and functions remains a substantial challenge for the neurosciences. Previous studies have shown a genetic basis for individual differences in mathematical functioning; however, the specific genes remain to be completely identified. In the present study, we explored the possibility that 2 functional polymorphisms in candidate genes could be associated with differences in arithmetical performance. METHODS: A computerized test to analyze performance in basic arithmetical calculations (additions and subtractions) was applied to 168 healthy young Colombian participants using the PEBL (Psychology Experiment Building Language) battery. DNA samples were genotyped for 2 functional SNPs in candidate genes: brain-derived neurotrophic factor (BDNF)-Val66Met and catechol-O-methyltransferase (COMT)-Val158Met. RESULTS: We found significant differences for arithmetical processing scores between genotypes. For BDNF, Val/Val subjects had a worse performance (p value: 0.025) and for COMT, Val/Val carriers had a better performance (p value: 0.006). A multivariate model, including both BDNF and COMT genes, accounted for 7.1% of the variance in math processing scores. DISCUSSION: To our knowledge, this is the first study finding associations of polymorphisms in BDNF and COMT genes with quantitative measures of numerical aptitude in healthy young participants. A future study of other genes involved in neural plasticity could be helpful to identify genetic correlates of arithmetical functioning, which will be important for the understanding of normal human behaviors and related neuropsychiatric disorders.