We report that the DNA methylation profile of a child's neonatal whole blood can be significa... more We report that the DNA methylation profile of a child's neonatal whole blood can be significantly influenced by his or her mother's neonatal blood lead levels (BLL). We recruited 35 mother-infant pairs in Detroit and measured the whole blood lead (Pb) levels and DNA methylation levels at over 450,000 loci from current blood and neonatal blood from both the mother and the child. We found that mothers with high neonatal BLL correlate with altered DNA methylation at 564 loci in their children's neonatal blood. Our results suggest that Pb exposure during pregnancy affects the DNA methylation status of the fetal germ cells, which leads to altered DNA methylation in grandchildren's neonatal dried blood spots. This is the first demonstration that an environmental exposure in pregnant mothers can have an epigenetic effect on the DNA methylation pattern in the grandchildren.
Epigenetics : official journal of the DNA Methylation Society, Jan 5, 2015
Prenatal exposure to neurotoxicants such as Lead (Pb) may cause stable changes in the DNA methyla... more Prenatal exposure to neurotoxicants such as Lead (Pb) may cause stable changes in the DNA methylation (5mC) profile of the fetal genome. However few studies have examined its effect on the DNA de-methylation pathway, specifically the dynamic changes of the 5-hydroxymethylcytosine (5hmC) profile. Therefore, in this study, we investigate the relationship between Pb exposure and 5mC and 5hmC modifications during early development. To study the changes in the 5hmC profile, we use a novel modification of the Infinium™ Human methylation 450K assay (Illumina, Inc.), which we named HMeDIP-450K assay, in an in vitro human embryonic stem cell model of Pb-exposure. We model Pb-exposure associated 5hmC changes as clusters of correlated, adjacent CpG sites, which are co-responding to Pb. We further extend our study to look at Pb-dependent changes in high density 5hmC regions in umbilical cord blood DNA from 48 mother-infant pairs from the Early Life Exposure in Mexico to Environmental Toxicants ...
In a recent perspective in this journal, Herb (2014) discussed how epigenetics is a possible mech... more In a recent perspective in this journal, Herb (2014) discussed how epigenetics is a possible mechanism to circumvent Charles Darwin's "special difficulty" in using natural selection to explain the existence of the sterile-fertile dimorphism in eusocial insects. Darwin's classic book "On the Origin of Species by Means of Natural Selection" explains how natural selection of the fittest individuals in a population can allow a species to adapt to a novel or changing environment. However, in bees and other eusocial insects, such as ants and termites, there exist two or more castes of genetically similar females, from fertile queens to multiple sub-castes of sterile workers, with vastly different phenotypes, lifespans, and behaviors. This necessitates the selection of groups (or kin) rather than individuals in the evolution of honeybee hives, but group and kin selection theories of evolution are controversial and mechanistically uncertain. Also, group selection would seem to be prohibitively inefficient because the effective population size of a colony is reduced from thousands to a single breeding queen. In this follow-up perspective, we elaborate on possible mechanisms for how a combination of both epigenetics, specifically, the selection of metastable epialleles, and genetics, the selection of mutations generated by the selected metastable epialleles, allows for a combined means for selection amongst the fertile members of a species to increase colony fitness. This "intra-caste evolution" hypothesis is a variation of the epigenetic directed genetic error hypothesis, which proposes that selected metastable epialleles increase genetic variability by directing mutations specifically to the epialleles. Natural selection of random metastable epialleles followed by a second round of natural selection of random mutations generated by the metastable epialleles would allow a way around the small effective population size of eusocial insects.
In this paper, we tested the hypothesis that early life lead (Pb) exposure associated DNA methyla... more In this paper, we tested the hypothesis that early life lead (Pb) exposure associated DNA methylation (5 mC) changes are dependent on the sex of the child and can serve as biomarkers for Pb exposure. In this pilot study, we measured the 5mC profiles of DNA extracted from dried blood spots (DBS) in a cohort of 43 children (25 males and 18 females; ages from 3 months to 5 years) from Detroit. Result & Discussion: We found that the effect of Pb-exposure on the 5-mC profiles can be separated into three subtypes: affected methylation loci which are conserved irrespective of the sex of the child (conserved); affected methylation loci unique to males (male-specific); and affected methylation loci unique to females (female-specific).
We report that the DNA methylation profile of a child's neonatal whole blood can be significa... more We report that the DNA methylation profile of a child's neonatal whole blood can be significantly influenced by his or her mother's neonatal blood lead levels (BLL). We recruited 35 mother-infant pairs in Detroit and measured the whole blood lead (Pb) levels and DNA methylation levels at over 450,000 loci from current blood and neonatal blood from both the mother and the child. We found that mothers with high neonatal BLL correlate with altered DNA methylation at 564 loci in their children's neonatal blood. Our results suggest that Pb exposure during pregnancy affects the DNA methylation status of the fetal germ cells, which leads to altered DNA methylation in grandchildren's neonatal dried blood spots. This is the first demonstration that an environmental exposure in pregnant mothers can have an epigenetic effect on the DNA methylation pattern in the grandchildren.
Epigenetics : official journal of the DNA Methylation Society, Jan 5, 2015
Prenatal exposure to neurotoxicants such as Lead (Pb) may cause stable changes in the DNA methyla... more Prenatal exposure to neurotoxicants such as Lead (Pb) may cause stable changes in the DNA methylation (5mC) profile of the fetal genome. However few studies have examined its effect on the DNA de-methylation pathway, specifically the dynamic changes of the 5-hydroxymethylcytosine (5hmC) profile. Therefore, in this study, we investigate the relationship between Pb exposure and 5mC and 5hmC modifications during early development. To study the changes in the 5hmC profile, we use a novel modification of the Infinium™ Human methylation 450K assay (Illumina, Inc.), which we named HMeDIP-450K assay, in an in vitro human embryonic stem cell model of Pb-exposure. We model Pb-exposure associated 5hmC changes as clusters of correlated, adjacent CpG sites, which are co-responding to Pb. We further extend our study to look at Pb-dependent changes in high density 5hmC regions in umbilical cord blood DNA from 48 mother-infant pairs from the Early Life Exposure in Mexico to Environmental Toxicants ...
In a recent perspective in this journal, Herb (2014) discussed how epigenetics is a possible mech... more In a recent perspective in this journal, Herb (2014) discussed how epigenetics is a possible mechanism to circumvent Charles Darwin's "special difficulty" in using natural selection to explain the existence of the sterile-fertile dimorphism in eusocial insects. Darwin's classic book "On the Origin of Species by Means of Natural Selection" explains how natural selection of the fittest individuals in a population can allow a species to adapt to a novel or changing environment. However, in bees and other eusocial insects, such as ants and termites, there exist two or more castes of genetically similar females, from fertile queens to multiple sub-castes of sterile workers, with vastly different phenotypes, lifespans, and behaviors. This necessitates the selection of groups (or kin) rather than individuals in the evolution of honeybee hives, but group and kin selection theories of evolution are controversial and mechanistically uncertain. Also, group selection would seem to be prohibitively inefficient because the effective population size of a colony is reduced from thousands to a single breeding queen. In this follow-up perspective, we elaborate on possible mechanisms for how a combination of both epigenetics, specifically, the selection of metastable epialleles, and genetics, the selection of mutations generated by the selected metastable epialleles, allows for a combined means for selection amongst the fertile members of a species to increase colony fitness. This "intra-caste evolution" hypothesis is a variation of the epigenetic directed genetic error hypothesis, which proposes that selected metastable epialleles increase genetic variability by directing mutations specifically to the epialleles. Natural selection of random metastable epialleles followed by a second round of natural selection of random mutations generated by the metastable epialleles would allow a way around the small effective population size of eusocial insects.
In this paper, we tested the hypothesis that early life lead (Pb) exposure associated DNA methyla... more In this paper, we tested the hypothesis that early life lead (Pb) exposure associated DNA methylation (5 mC) changes are dependent on the sex of the child and can serve as biomarkers for Pb exposure. In this pilot study, we measured the 5mC profiles of DNA extracted from dried blood spots (DBS) in a cohort of 43 children (25 males and 18 females; ages from 3 months to 5 years) from Detroit. Result & Discussion: We found that the effect of Pb-exposure on the 5-mC profiles can be separated into three subtypes: affected methylation loci which are conserved irrespective of the sex of the child (conserved); affected methylation loci unique to males (male-specific); and affected methylation loci unique to females (female-specific).
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Papers by Arko Sen