Mosaic loss of the Y chromosome and men's health

Fukami, Maki; Miyado, Mami

doi:10.1002/rmb2.12445

Cited by 10 publications

(3 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Mosaic loss of chromosome Y (mLOY), the most common form of aneuploidy relating to genome instability in non-malignant diseases, can occur in all age groups (12) but is most prevalent in older males. Smoking is a potential risk factor for mLOY in blood cells (13).…”

Section: )mentioning

confidence: 99%

Association between mosaic loss of chromosome Y and pulmonary fibrosis susceptibility and severity

Wang,

Hadad,

Moss

et al. 2024

Preprint

View full text Add to dashboard Cite

BackgroundPulmonary fibrosis (PF) is a rare lung disease with diverse pathogenesis and multiple interconnected underlying biological mechanisms. Mosaic loss of chromosome Y (mLOY) is one of the most common forms of acquired chromosome abnormality in men, which has been reported to be associated with increased risk of various chronic progressive diseases including fibrotic diseases. However, the exact role of mLOY in the development of PF remains elusive and to be elucidated.MethodsWe adopted three complementary approaches to explore the role of mLOY in the pathogenesis of PF. We used copy number on chromosome Y to estimate mLOY comparing patients in PROFILE and gnomAD cohorts and between cases and control patients from the GE100KGP cohort. Correlation of mLOY with demographic and clinical variables was tested using patients from PROFILE cohort. Lung single-cell transcriptomic data were analysed to assess the cell types implicated in mLOY. We performed Mendelian randomisation to examine the causal relationship between mLOY, IPF, and telomere length.ResultsThe genetic analysis suggests that mLOY is found in PF from both case cohorts but when compared with an age matched population the effect is minimal (P = 0.0032). mLOY is related to age (P = 0.00021) and shorter telomere length (P = 0.0081) rather than PF severity or progression. Single-cell analysis indicates that mLOY appears to be found primarily in immune cells and appears to be related to presence and severity of fibrosis. Mendelian randomisation demonstrates that mLOY is not on the causal pathway for IPF, but partial evidence supports that telomere shortening is on the causal pathway for mLOY.ConclusionOur study confirms the existence of mLOY in PF patients and suggests that mLOY is not a major driver of IPF. The combined evidence suggests a triangulation model where telomere shortening leads to both IPF and mLOY.

show abstract

Section: )mentioning

confidence: 99%

Association between mosaic loss of chromosome Y and pulmonary fibrosis susceptibility and severity

Wang,

Hadad,

Moss

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…Loss of Y chromosome (LOY) is one of the most common somatic mutations that can occur at any stage of a healthy male individual's life as a normal aging process, and its frequency increases over time. Gradually expanding studies have revealed that LOY may be associated with a variety of health issues, such as cancer, cardiovascular disease, age-related disorders, and smoking status [14][15][16]. In recent years, methods for the detection and analysis of LOY have been updated and re ned, including traditional uorescent in situ hybridization (FISH) [17], as well as emerging Illumina SNP genotyping arrays, nextgeneration sequencing technologies [14,16], qPCR[18], multiplex uorescent PCR [19], and the rst absolute quanti cation of LOY percentage using droplet digital PCR (ddPCR) given by Danielsson et al [20].…”

Section: Introductionmentioning

confidence: 99%

Characterization of loss of Y chromosome in peripheral blood of Chinese Han male patients with schizophrenia

Jiang

Song

et al. 2023

Preprint

View full text Add to dashboard Cite

Background Schizophrenia has a global prevalence of 1% and is a threat to life expectancy and mortality. There is growing evidence that the risk of developing this disorder is higher in males than in females and tends to develop in early adulthood. The Y chromosome is thought to be involved in biological processes other than sex determination and spermatogenesis that affect male health and disease. Studies have found that Loss of Y chromosome (LOY) in peripheral blood is associated with a variety of diseases, cancer and increased all-cause mortality, so an analysis of the relationship between LOY and schizophrenia is warranted. Methods The study included 442 Chinese males (271 patients with schizophrenia vs 171 controls). The copy numbers of Y and X chromosome were detected by the positive droplets targeted with Amelogenin gene (AMEL) located on the Y chromosome and X chromosome (AMELY and AMELX) using droplet digital PCR (ddPCR), respectively. The LOY percentage was defined as the difference between the concentration of AMELX and the concentration of AMELY divided by the concentration of AMELX, denoted as (X - Y)/X. Results There was no significant difference in the presence of LOY between the schizophrenia and control groups in Chinese Han population. A remarkable correlation was found between the disease duration and (X - Y)/X ratio by using the mean (R2 = 0.51, p = 0.032). The logistic regression analysis implied that the risk of suffering LOY increases by 5.8% and 5.7% per year with age at onset and duration of the disease, respectively (ponset = 0.013, pduration = 0.017). Conclusions For the Chinese Han population, age of onset and duration of schizophrenia might be risk factors for LOY development in peripheral blood. More clinical information and larger sample size need to be collected for more in-depth and specific analyses.

show abstract

“…Infertility is a prevalent disorder that affects over 15% of couples worldwide, with various causes such as meiotic arrest due to cytogenetic shuffling, toxins, and other physical factors ( 1 – 4 ). Among the genetic causes of male infertility, chromosomal abnormalities have been reported in approximately 6% of cases, and microdeletions in the Y chromosome account for spermatogenic failure in 5-20% of men with azoospermia ( 3 , 5 – 8 ). The most common structural Y chromosome aberrations in infertile men with azoospermia have been reported to be an isodicentric or isochromosome Y, with duplications in the Yp region and deletions in the Yq region, or vice versa ( 9 – 12 ).…”

mentioning

confidence: 99%

Editorial: Molecular and cytogenetic research advances in human reproduction - volume II

et al. 2023

View full text Add to dashboard Cite

Editorial on the Research Topic Molecular and cytogenetic research advances in human reproductionvolume IIInfertility is a prevalent disorder that affects over 15% of couples worldwide, with various causes such as meiotic arrest due to cytogenetic shuffling, toxins, and other physical factors (1-4). Among the genetic causes of male infertility, chromosomal abnormalities have been reported in approximately 6% of cases, and microdeletions in the Y chromosome account for spermatogenic failure in 5-20% of men with azoospermia (3, 5-8). The most common structural Y chromosome aberrations in infertile men with azoospermia have been reported to be an isodicentric or isochromosome Y, with duplications in the Yp region and deletions in the Yq region, or vice versa (9-12). The human X and Y chromosomes pair at their distal short arms during male meiosis, with the telomeres first approaching each other during the zygotene stage of meiotic prophase (13, 14). As pachytene progresses, a paired segment is formed, and a synaptonemal complex (SC) which, on average, extends to about one-third of the total length of the Y chromosome (15-17).Recently, pathogenic genetic mutations have been identified in individuals suffering from reproductive disorders; these mutations are generally detected in the genes mainly involved in germ cell development and other reproductive processes (18-21). Nevertheless, thousands of functionally relevant genes are expressed in human testes and ovaries, and malfunctioning of even a single gene can potentially cause infertility (22)(23)(24). Although the overall mechanistic contribution of specific genes has been studied in animal models, more attention is now being paid to clinically detected alterations in DNA, which include mutations potentially affecting gene regulatory sequences such as the 3'UTR (25, 26). However, the impact of mutations in gene 3'UTR sequences may not be adequately recognized in current sequencing analyses. This provides a potentially massive gap between Frontiers in Endocrinology frontiersin.org 01

show abstract

Mosaic loss of the Y chromosome and men's health

Cited by 10 publications

References 44 publications

Association between mosaic loss of chromosome Y and pulmonary fibrosis susceptibility and severity

Association between mosaic loss of chromosome Y and pulmonary fibrosis susceptibility and severity

Characterization of loss of Y chromosome in peripheral blood of Chinese Han male patients with schizophrenia

Editorial: Molecular and cytogenetic research advances in human reproduction - volume II

Contact Info

Product

Resources

About