The 3D genome landscape: Diverse chromosomal interactions and their functional implications

Fleck, Katherine; Raj, Romir; Erceg, Jelena

doi:10.3389/fcell.2022.968145

Cited by 2 publications

(2 citation statements)

References 178 publications

(306 reference statements)

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“…In addition to cis-acting regulation, emerging evidence is showing how 3-D organization of the chromosomes influences gene expression and co-regulation through trans-acting mechanisms (Fleck et al, 2022), implicating autosomal regulation of genes on the X, and vice versa.…”

Section: Introductionmentioning

confidence: 99%

Sex differences in the associations of genetic, sociodemographic and cardiovascular risk factors with depression in the Canadian Longitudinal Study on Aging (CLSA)

Théberge

Dennis

2023

Preprint

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Major depressive disorder (MDD) is a leading cause of morbidity and disability worldwide, with approximately twice as many women reported to have a lifetime occurrence of MDD than men. MDD is a polygenic trait, wherein hundreds to thousands of common genetic variants with small effect sizes contribute to risk of disease. This study investigated sex differences in the risk factor comorbidity and genetic architecture of MDD in over 16,000 people aged 45-85 from the Canadian Longitudinal Study on Aging (CLSA), with 21% of females (n=1,741) and 12% of males (n=1,055) coded with MDD. Polygenic risk scores (PRS) for individuals were made using sex-stratified and non-sex-specific ("both-sexes") UK Biobank genome-wide association study summary statistics data. Odds of MDD for the sex-specific PRSs, socioeconomic, lifestyle and clinical risk factors associated with cardiovascular disease risk were assessed using a multivariable logistic regression model for each sex. Significant sex-specific risk factor associations with odds of MDD were found in females (history of ischemic heart disease (OR 1.52 (1.14-2.01), hypothyroidism (OR 1.42 (1.25-1.63), not being partnered (OR 1.34 (1.17-1.52)), having diabetes (OR 1.30 (1.11-1.52)), and higher female sex-specific autosomal PRS (OR 1.10 (1.04-1.16))) and males (high blood pressure, OR 1.35 (1.04-1.47)). Significant differences were observed in the proportion of variables that contributed to the most to each model, evaluated by relative pseudo-R2 values. Age contributed the most to the model for both sexes (46.9% for females, 32.5% for males), wherein younger age was associated with higher odds of MDD. These results underscore the relevance for sex-disaggregating analyses of complex traits, like MDD, and the incorporation of clinical variables into models of MDD, in applications such as early detection and primary prevention.

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Section: Introductionmentioning

confidence: 99%

Sex differences in the associations of genetic, sociodemographic and cardiovascular risk factors with depression in the Canadian Longitudinal Study on Aging (CLSA)

Théberge

Dennis

2023

Preprint

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“…Functionally, the three-dimensional genome organization regulates gene expression via crosstalk between DNA elements located in specific chromosomal territories. Regulatory nucleus organization may involve intra- and interchromosomal interactions, with genomic activity being situated in specific hubs [ 8 ]. The points of overlap or intermingling of chromosomal territories are metaphorically called ‘kissing chromosomes‘ and, in general, this phenomenon has been termed nonhomologous chromosomal contacts (NHCCs) [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

Nonhomologous Chromosome Interactions in Prophase I: Dynamics of Bizarre Meiotic Contacts in the Alay Mole Vole Ellobius alaicus (Mammalia, Rodentia)

Matveevsky

Bakloushinskaya

Tambovtseva

et al. 2022

Genes

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Nonhomologous chromosome interactions take place in both somatic and meiotic cells. Prior to this study, we had discovered special contacts through the SYCP3 (synaptonemal complex protein 3) filament between the short arms of nonhomologous acrocentrics at the pachytene stage in the Alay mole vole, and these contacts demonstrate several patterns from proximity to the complete fusion stage. Here, we investigated the nonhomologous chromosome contacts in meiotic prophase I. It turned out that such contacts do not introduce changes into the classic distribution of DNA double-strand breaks. It is noteworthy that not all meiotic contacts were localized in the H3k9me3-positive heterochromatic environment. Both in the mid zygotene and in the early–mid diplotene, three types of contacts (proximity, touching, and anchoring/tethering) were observed, whereas fusion seems to be characteristic only for pachytene. The number of contacts in the mid pachytene is significantly higher than that in the zygotene, and the distance between centromeres in nonhomologous contacts is also the smallest in mid pachytene for all types of contacts. Thus, this work provides a new insight into the behavior of meiotic contacts during prophase I and points to avenues of further research.

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The 3D genome landscape: Diverse chromosomal interactions and their functional implications

Cited by 2 publications

References 178 publications

Sex differences in the associations of genetic, sociodemographic and cardiovascular risk factors with depression in the Canadian Longitudinal Study on Aging (CLSA)

Sex differences in the associations of genetic, sociodemographic and cardiovascular risk factors with depression in the Canadian Longitudinal Study on Aging (CLSA)

Nonhomologous Chromosome Interactions in Prophase I: Dynamics of Bizarre Meiotic Contacts in the Alay Mole Vole Ellobius alaicus (Mammalia, Rodentia)

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