Y chromosome in health and diseases

Lau, Yun‐Fai Chris

doi:10.1186/s13578-020-00452-w

Cited by 14 publications

(7 citation statements)

References 67 publications

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“…Interestingly, among the 46 genes with bimodality in more than one tumor type, 12 are mapped to the Y chromosome (p<10 -5 ), an unexpected observation due to the low gene density in this chromosome. As reviewed by Lau (2020 ), some genes on the Y chromosome have dosage-sensitive functions, which might be related to a bimodal expression pattern. This remains to be further explored.…”

Section: Discussionmentioning

confidence: 99%

An integrated approach to identify bimodal genes associated with prognosis in câncer

et al. 2021

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Bimodal gene expression (where a gene expression distribution has two maxima) is associated with phenotypic diversity in different biological systems. A critical issue, thus, is the integration of expression and phenotype data to identify genuine associations. Here, we developed tools that allow both: i) the identification of genes with bimodal gene expression and ii) their association with prognosis in cancer patients from The Cancer Genome Atlas (TCGA). Bimodality was observed for 554 genes in expression data from 25 tumor types. Furthermore, 96 of these genes presented different prognosis when patients belonging to the two expression peaks were compared. The software to execute the method and the corresponding documentation are available at the Data access section.

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Section: Discussionmentioning

confidence: 99%

An integrated approach to identify bimodal genes associated with prognosis in câncer

et al. 2021

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“…The presence or absence of Y chromosome, epigenetic modifications and the unequal dosage of X chromosome partly affect the sexual dimorphism present in health and disease, as well as sex hormone contribution [ 1 , 2 ]. It has been established that the Y chromosome, considered a genetic wasteland so far, plays a role in determining these differences in most common pathological conditions such as cancer, Alzheimer, Parkinson and cardiovascular diseases [ 3 ]. In particular, the sexual dimorphism in cancer incidence and survival, where males show a higher risk and a lower survival than females, has been attributed to circulating hormones, sex chromosomes, as well as to differences in DNA damage response pathways [ 4 , 5 ].…”

Section: Introductionmentioning

confidence: 99%

CRISPR/Cas9 mediated Y-chromosome elimination affects human cells transcriptome

Celli,

Gasparini,

Biino

et al. 2024

Cell Biosci

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Background Sexual dimorphism represents a key concept in the comprehension of molecular processes guiding several sex-specific physiological and pathological mechanisms. It has been reported that genes involved in many disorders show a sex-dependent expression pattern. Moreover, the loss of Y chromosome (LOY), found to be a physiological age-driven phenomenon, has been linked to many neurodegenerative and autoimmune disorders, and to an increased cancer risk. These findings drove us towards the consideration that LOY may cause the de-regulation of disease specific networks, involving genes located in both autosomal and sex chromosomes. Results Exploiting the CRISPR/Cas9 and RNA-sequencing technologies, we generated a Y-deficient human cell line that has been investigated for its gene expression profile. Our results showed that LOY can influence the transcriptome displaying relevant enriched biological processes, such as cell migration regulation, angiogenesis and immune response. Interestingly, the ovarian follicle development pathway was found enriched, supporting the female-mimicking profile of male Y-depleted cells. Conclusion This study, besides proposing a novel approach to investigate sex-biased physiological and pathological conditions, highlights new roles for the Y chromosome in the sexual dimorphism characterizing human health and diseases. Moreover, this analysis paves the way for the research of new therapeutic approaches for sex dimorphic and LOY-related diseases.

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“…H-Y antigens, which are proteins encoded by Y-chromosome, are important minor histocompatibility antigens. Y-chromosome is the sex-determining chromosome and contains several genes that are involved in the differentiation of male-specific organs, spermatogenesis, various cytokines and the cell cycle 9 . Since Y-chromosome is specific to males, H-Y antigens are potential targets of GVHD in transplants between female donors and male recipients (female-to-male allo-HCT).…”

Section: Introductionmentioning

confidence: 99%

“…The Y chromosome is the sex-determining chromosome and contains several genes that are involved in the differentiation of male-specific organs, spermatogenesis, various cytokines, and the cell cycle. 9 Because the Y chromosome is specific to males, H-Y antigens are potential targets of GVHD in transplantations involving female donors and male recipients (female-to-male allo-HCT). The combination of a male recipient and female donor has been associated with an increased risk of GVHD and inferior survival but a lower relapse rate in female-to-male allo-HCT in selected situations, suggesting that H-Y antigens may play an important role as a target of the GVL effect.…”

Section: Introductionmentioning

confidence: 99%

Deletion of Y chromosome before allogeneic hematopoietic stem cell transplantation in male recipients with female donors

et al. 2022

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The graft-versus-leukemia (GVL) effect is one of the curative mechanisms of allogeneic hematopoietic stem cell transplantation (allo-HCT). H-Y antigens, which are encoded by Y chromosome, are important targets of the GVL effect. Thus, deletion of the Y chromosome (del[Y]) might cause the GVL effect to deteriorate in a transplantation involving a female donor and male recipient, although the clinical significance of the del(Y) group remains to be elucidated. In this study, we evaluated adult male patients who underwent allo-HCT between 2010 and 2019 in Japan. There were 155 cases in the del(Y) group and 4149 cases without del(Y) who underwent female-to-male allo-HCT. Del(Y) was significantly associated with inferior overall survival (hazard ratio [HR], 1.24; 95% confidence interval [CI], 1.00-1.53; P = .049) and an increased risk of relapse (HR, 1.40; 95% CI, 1.08-1.80; P = .0098) in multivariate analyses. There was no significant difference in nonrelapse mortality between recipients with and without del(Y) (HR, 1.08; 95% CI, 0.769-1.51; P = .67). In contrast, del(Y) was not significantly associated with any clinical outcomes in the cohort of male-to-male allo-HCT. A higher incidence of relapse might have been caused by attenuation of the GVL effect resulting from a lack of H-Y antigens. Because a GVL effect resulting from sex mismatch may not be expected in men with del(Y) who undergo allo-HCT with a female donor, additional post–allo-HCT strategies might be required to prevent disease relapse.

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Y chromosome in health and diseases

Cited by 14 publications

References 67 publications

An integrated approach to identify bimodal genes associated with prognosis in câncer

An integrated approach to identify bimodal genes associated with prognosis in câncer

CRISPR/Cas9 mediated Y-chromosome elimination affects human cells transcriptome

Deletion of Y chromosome before allogeneic hematopoietic stem cell transplantation in male recipients with female donors

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