Biology subjects

Derakhshan, M.

Publications and source records attributed to Derakhshan, M..

3 recordsLinked to original sources

bioRxiv2022

DNA methylation at the suppressor of cytokine signaling 3 (SOCS3) gene influences height in childhood

Human height is strongly influenced by genetics but the contribution of modifiable epigenetic factors is under-explored, particularly in low and middle-income countries (LMIC). We investigated links between blood DNA methylation and child height in four LMIC cohorts (n=1927) and identified a robust association at three CpGs in the suppressor of cytokine signalling 3 (SOCS3) gene which replicated in a high-income country cohort (n=879). SOCS3 methylation (SOCS3m) - height associations were independent of genetic effects. Mendelian randomization analysis confirmed a causal effect of SOCS3m on height. In longitudinal analysis in a LMIC cohort, SOCS3m explained a maximum 9.5% of height variance in mid-childhood while the variance explained by height polygenic risk score increased from birth to 21 years (2% to 18%). Childrens SOCS3m was associated with prenatal maternal folate and socio-economic status. In-vitro characterization confirmed a regulatory effect of SOCS3m on gene expression. Our findings suggest that epigenetic modifications may play an important role in driving child height in LMIC.

genomics↗

bioRxiv2021

Tissue- and ethnicity-independent hypervariable DNA methylation states show evidence of establishment in the early human embryo

We analysed DNA methylation data from 30 datasets comprising 3,474 individuals, 19 tissues and 8 ethnicities at CpGs covered by the Illumina450K array. We identified 4,143 hypervariable CpGs ("hvCpGs") with methylation in the top 5% most variable sites across multiple tissues and ethnicities. hvCpG methylation was influenced but not determined by genetic variation, and was not linked to probe reliability, epigenetic drift, age, sex or cell heterogeneity effects. hvCpG methylation tended to covary across tissues derived from different germ-layers and hvCpGs were enriched for associations with periconceptional environment, proximity to ERV1 and ERVK retrovirus elements and parent-of-origin-specific methylation. They also showed distinctive methylation signatures in monozygotic twins. Together, these properties position hvCpGs as strong candidates for studying how stochastic and/or environmentally influenced DNA methylation states which are established in the early embryo and maintained stably thereafter can influence life-long health and disease.

genomics↗

bioRxiv2019

Game Theory Applications in Host-Microbe Interactions: Mycobacterium tuberculosis infection as an example

The game theory describes the interactions between two players and the pay-off from wining, losing or compromising. Mycobacterium tuberculosis (Mtb)-host interactions were used as an example for the application of the game theory to describe and predict the possibilities of victory for any players. The gene expression for eight main markers of host response and three Mtb virulence factors were assessed in broncho-alveolar lavage of TB+ and TB- patients. The game theory showed that a variety of paths exist that players can use, in response to the behaviour of the counterpart. Briefly, according to the "Nash equilibrium", Ag85B is the main virulence factor for Mtb in active phase, however it is the most immunogenic factor if the host can respond by high expression of T-bet and iNOS. In this situation, Mtb can express high levels of ESAT-6 and CFP10 and change the game to the latency, in which host responses by medium expression of T-bet and iNOS and medium level of TGF-{beta} and IDO. Consistently, The IDO expression was 134-times higher in TB+s than the TB-s, and the T-bet expression, ~200-times higher in the TB-s than the TB+s. Furthermore, Mtb-Ag85B had a strong positive association with CCR2, T-bet and iNOS, but had a negative correlation with IDO.

microbiology↗