Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Candidate transcriptomic sources of inbreeding depression in Drosophila melanogaster

ABSTRACT: The genomic causes of inbreeding depression are poorly known. Several studies have found widespread transcriptomic alterations in inbred organisms, but it remains unclear which of these alterations are causes of the depression and which are mere responses to the ensuing physiological stress. We made a c-DNA microarray analysis in Drosophila melanogaster attempting to differentiate causes from responses of inbreeding depression. The rationale of the experiment was that, while depression is a general phenomenon producing similar consequences in different inbred lines, its first genetic causes would be different for each inbred line, as they are expected to be caused by the fixation of rare deleterious genes. Many changes in expression were common to all sets, but fourteen genes, grouped in four expression clusters, showed strong set-specific changes, and were therefore candidates to be sources of the inbreeding depression observed. We took four sets of inbred sublines, each set descending from a different founding pair obtained from a large outbred stock, and compared the expression of the three most depressed sublines and the three least depressed sublines from each set.

ORGANISM(S): Drosophila melanogaster

SUBMITTER: Humberto Quesada

PROVIDER: E-GEOD-47176 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Background: Selective serotonin reuptake inhibitors (SSRIs), used to treat prenatal maternal depression, have been associated with neurobehavioral disturbances in exposed neonates, though the underlying molecular mechanisms remain poorly understood. In utero exposure to SSRIs may have an effect on DNA methylation (DNAme) in the human placenta, which is an epigenetic mark that is established during development and is associated with gene expression. Methods: Chorionic villus samples from 64 human placentas were profiled with the Illumina MethylationEPIC BeadChip and clinical assessments of maternal mood were collected at multiple time points during pregnancy. Case distribution was 20 SSRI-exposed cases and 44 SSRI non-exposed cases. Maternal depression using a mean maternal Hamilton Depression score >8 to indicate symptomatic depressed mood (“maternally-depressed”) further classified cases into SSRI-exposed, maternally-depressed (n=14); SSRI-exposed, not maternally-depressed (n=6); SSRI non-exposed, maternally-depressed (n=20); and SSRI non-exposed, not maternally-depressed (n=24). To provide a replication cohort, Illumina 450K DNAme profiles were obtained from 34 additional cases from an independent cohort (n=17 SSRI-exposed, n=17 SSRI non-exposed). Results: No CpGs were differentially methylated at FDR < 0.05 comparing SSRI-exposed to non-exposed placentas, while adjusting for mean maternal Hamilton Depression score, nor comparing SSRI-exposed maternally-depressed to SSRI-non-exposed maternally-depressed cases. At a relaxed threshold of FDR < 0.25, five CpGs were differentially methylated (|Δβ| > 0.03) by SSRI exposure status. Four of these CpGs were covered by the 450K array and were examined in the replication cohort, but none replicated. Amongst SSRI non-exposed cases, No CpGs were differentially methylated (FDR < 0.25) comparing maternally depressed to not depressed cases. In sex-stratified analyses for SSRI-exposed versus non-exposed cases (females n=31; males n=33), three additional CpGs in females, but none in males, were differentially methylated at the relaxed FDR < 0.25 cut-off. Conclusions: We did not observe large-scale alterations of DNAme in placentas exposed to maternal SSRI treatment compared to placentas with no SSRI exposure. We also found no evidence for altered DNAme in maternal depression-exposed versus depression non-exposed placentas. This novel work in a prospectively-recruited cohort with clinician-ascertained SSRI exposure and mood assessments would benefit from future replication.

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Candidate transcriptomic sources of inbreeding depression in Drosophila melanogaster

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