First Report on Karyotypic, Morphometric and Meiotic Analysis of a Predatory Bombardier Beetle Pherosophus catoirai (Coleoptera: Carabidae) from Jammu region of Outer Himalayas, India

Chromosomal studies and manual karyotyping are the aged techniques for determining the identity of a species on evolutionary scale; however, these techniques are simple, reliable and inexpensive to authenticate the existence of a particular species. In the present work, the chromosome complement and meiotic processes of a predatory bombardier beetle Pherosophus catoirai were investigated. This species presented 2n=35 as diploid chromosome number and the chromosomal formula was found to be 12m+8sm+12st+X0. Sex mechanism was X0 type with metacentric X chromosome. Y chromosome was absent in this species. Karyotype revealed small chromosomes except X chromosome which is found to be largest in the spermatogonial metaphase stage. Meiotic stages were pachytene, diplotene, diakinesis and metaphase-I. Present study may find importance to analyse evolution of chromosomes in order Coleoptera particularly in family Carabidae.

Mosaic loss of chromosome Y in aged human microglia.

Mosaic loss of chromosome Y (LOY) is a particularly common acquired structural mutation in the leukocytes of aging men and it has been shown to correlate with several age-related diseases including Alzheimer's disease (AD). To derive the molecular basis of LOY in brain cells, we create an integrated resource by aggregating data from 21 single-cell and single-nuclei RNA brain studies, yielding 763,410 cells to investigate the presence and cell-type specific burden of LOY. We created robust quantification metrics for assessing LOY, which were validated using a multi-modal dataset. Using this new resource and LOY-quantification approach, we found that LOY frequencies differed widely between CNS cell-types and individual donors. Among five common neural cell types, microglia were most affected by LOY (7.79%, n=41,949), while LOY in neurons was rare (0.48%, n=220,010). Differential gene expression analysis in microglia found 188 autosomal genes, 6 X-linked genes, and 11 pseudoautosomal genes, pointing to broad dysregulation in lipoprotein metabolism, inflammatory response, and antigen processing that coincides with loss of Y. To our knowledge, we provide the first evidence of LOY in the microglia, and highlight its potential roles in aging and the pathogenesis of neurodegenerative disorders such as AD.

Leukocytes with chromosome Y loss have reduced abundance of the cell surface immunoprotein CD99

Mosaic loss of chromosome Y (LOY) in immune cells is a male-specific mutation associated with increased risk for morbidity and mortality. The CD99 gene, positioned in the pseudoautosomal regions of chromosomes X and Y, encodes a cell surface protein essential for several key properties of leukocytes and immune system functions. Here we used CITE-seq for simultaneous quantification of CD99 derived mRNA and cell surface CD99 protein abundance in relation to LOY in single cells. The abundance of CD99 molecules was lower on the surfaces of LOY cells compared with cells without this aneuploidy in all six types of leukocytes studied, while the abundance of CD proteins encoded by genes located on autosomal chromosomes were independent from LOY. These results connect LOY in single cells with immune related cellular properties at the protein level, providing mechanistic insight regarding disease vulnerability in men affected with mosaic chromosome Y loss in blood leukocytes.

Interpretation of DNA data within the context of UK forensic science — investigation

This article is the second part of a review of the interpretation of DNA data in forensic science. The first part describes the evaluation of autosomal profile for criminal trials where an evidential weight is assigned to the profile of a person of interest (POI) and a crime-scene profile. This part describes the state of the art and future advances in the interpretation of forensic DNA data for providing intelligence information during an investigation. Forensic DNA is crucial in the investigative phase of an undetected crime where a POI needs to be identified. A sample taken from a crime scene is profiled using a range of forensic DNA tests. This review covers investigation using autosomal profiles including searching national and international crime and reference DNA databases. Other investigative methodologies described are kinship analysis; familial searching; Y chromosome (Y-STR) and mitochondrial (mtDNA) profiles; appearance prediction and geographic ancestry; forensic genetic genealogy; and body identification. For completeness, the evaluation of Y-STRs, mtDNA and kinship analysis are briefly described. Taken together, parts I and II, cover the range of interpretation of DNA data in a forensic context.

Immune cells lacking Y chromosome show dysregulation of autosomal gene expression

Epidemiological investigations show that mosaic loss of chromosome Y (LOY) in leukocytes is associated with earlier mortality and morbidity from many diseases in men. LOY is the most common acquired mutation and is associated with aberrant clonal expansion of cells, yet it remains unclear whether this mosaicism exerts a direct physiological effect. We studied DNA and RNA from leukocytes in sorted- and single-cells in vivo and in vitro. DNA analyses of sorted cells showed that men diagnosed with Alzheimer’s disease was primarily affected with LOY in NK cells whereas prostate cancer patients more frequently displayed LOY in CD4 + T cells and granulocytes. Moreover, bulk and single-cell RNA sequencing in leukocytes allowed scoring of LOY from mRNA data and confirmed considerable variation in the rate of LOY across individuals and cell types. LOY-associated transcriptional effect (LATE) was observed in ~ 500 autosomal genes showing dysregulation in leukocytes with LOY. The fraction of LATE genes within specific cell types was substantially larger than the fraction of LATE genes shared between different subsets of leukocytes, suggesting that LOY might have pleiotropic effects. LATE genes are involved in immune functions but also encode proteins with roles in other diverse biological processes. Our findings highlight a surprisingly broad role for chromosome Y, challenging the view of it as a “genetic wasteland”, and support the hypothesis that altered immune function in leukocytes could be a mechanism linking LOY to increased risk for disease.

Deletions on Chromosome Y and Downregulation of the SRY Gene in Tumor Tissue Are Associated with Worse Survival of Glioblastoma Patients

Background: Biological causes of sex disparity seen in the prevalence of cancer, including glioblastoma (GBM), remain poorly understood. One of the considered aspects is the involvement of the sex chromosomes, especially loss of chromosome Y (LOY). Methods: Tumors from 105 isocitrate dehydrogenase (IDH) wild type male GBM patients were tested with droplet digital PCR for copy number changes of ten genes on chromosome Y. Decreased gene expression, a proxy of gene loss, was then analyzed in 225 IDH wild type GBM derived from TCGA and overall survival in both cohorts was tested with Kaplan–Meier log-rank analysis and maximally selected rank statistics for cut-off determination. Results: LOY was associated with significantly shorter overall survival (7 vs. 14.6 months, p = 0.0016), and among investigated individual genes survival correlated most prominently with loss of the sex-determining region Y gene (SRY) (10.8 vs. 14.8 months, p = 0.0031). Gene set enrichment analysis revealed that epidermal growth factor receptor, platelet-derived growth factor receptor, and MYC proto-oncogene signaling pathways are associated with low SRY expression. Conclusion: Our data show that deletions and reduced gene expression of chromosome Y genes, especially SRY, are associated with reduced survival of male GBM patients and connected to major susceptibility pathways of gliomagenesis.

Profil des patients vus dans une clinique externe de génétique médicale dans un centre universitaire à Belém, Pará, Amazon

La Génétique Médicale (GM) est devenue une spécialité médicale reconnue, avec des concepts et des approches importants dans le diagnostic et le traitement de nombreuses maladies courantes et rares. Les maladies génétiques suivent les modèles d’héritage, et peuvent être autosomiques récessives, dominantes autosomiques, liées au chromosome X ou au chromosome Y, ou multifactorielles. L’objectif de cette étude était de déterminer le profil des patients traités dans une clinique externe GM dans un Centre Universitaire de Belém, dans l’État du Pará. Les données ont été recueillies à partir des dossiers des patients, observés entre 2014 et 2019, à l’aide du propre questionnaire des chercheurs, avec des données analysées et compilées dans le cadre du programme Microsoft Excel. Un total de 101 dossiers médicaux ont été analysés, avec la prédominance des femelles (51 patients). De plus, la plupart des soins étaient pour les enfants (41,5 %). En ce qui concerne l’ethnicité, seules les variables « blanc » et « brun » ont été observées, avec une prévalence plus élevée de patients bruns (78 du total). En outre, Belém était la ville la plus répandue dans le naturel des patients (61 dossiers). Les spécialités avec le plus grand nombre de références à la clinique externe GM étaient l’endocrinologie et la neurologie, avec le retard de développement neuropsychomoteur étant le diagnostic le plus fréquent. Dans 42 dossiers médicaux, l’âge au diagnostic n’était pas présent. Sur les 101 patients, seulement 16 avaient des conseils génétiques et dans les 85 autres il n’y avait aucun dossier sur cette information. Enfin, l’âge maternel à la naissance n’a pas été trouvé dans la plupart des dossiers médicaux (absent dans 61,38%). Ainsi, il est important de développer un profil du patient vu dans une clinique externe GM, puisqu’il devient possible d’identifier les défaillances du service fourni, en plus d’adapter la relation médecin-patient.

Evaluation of the usefulness of saliva for mosaic loss of chromosome Y analysis

Mosaic loss of chromosome Y (mLOY) in leukocytes has attracted much attention as an emerging biomarker of aging and aging-related diseases. We evaluated the usefulness of saliva for mLOY analysis and showed that saliva-derived mLOY is significantly associated with aging and increased physical activity, but not with smoking. While these data support the robust association between saliva-derived mLOY and aging, caution is required when comparing data from saliva-derived and blood-derived mLOY.