Greater reproductive variance among males than among females is presented as a component of natural selection's influence in determining preferential treatment of males in the inheritance of wealth. In conjunction, the transmission of sex chromosomes and their attendant probabilities of carrying genes identical by descent are traced for several generations in order to illustrate a male bias in species whose male sex is heterogametic (XY) while the female sex is homogametic (XX). The effect of this bias on coefficients of relationship (direct and additive) leads to the hypothesis that the transmission of wealth (seen as an arbitrarily bestowable fitness advantage) along the male line is more efficient, in terms of maximizing ancestral fitness, than transmission along the female line.
Primary congenital glaucoma (PCG) is a childhood autosomal-recessive disorder caused by developmental defects in the trabecular meshwork and anterior chamber angle. These defects cause raised intraocular pressure (IOP) that damages the optic nerve and if left untreated, results in irreversible blindness. Mutations in CYP1B1 gene at the GLC3A locus (2p21) are associated with PCG. However, there has been very limited exploration of its promoter region. We resequenced the CYP1B1 promoter in a large cohort (n = 835) that included patients with PCG (n = 301), other primary glaucomas (primary open-angle glaucoma: n = 115 and primary angle closure glaucoma: n = 100) and unaffected controls (n = 319). We functionally characterized one associated variant by luciferase reporter assay using the trabecular meshwork (TM3) cell line. We found evidence of strong (P = 6.01 × 10−4) association of rs2567206 (T2805C) SNP in PCG and not in other primary glaucomas. Luciferase assay indicated a ∼90% reduction in CYP1B1 promoter activity in the risk-allele (C) compared to the other allele (T). The association of the risk allele was stronger in cases harboring homozygous CYP1B1 mutations (P = 3.42 × 10−12). The risk haplotype 'C-C-G' in the promoter had a strong non-random association to the previously characterized risk haplotype 'C-G-G-T-A' in the coding region. The independent effect of genotype at the promoter T2805C locus (P = 0.001), and the interaction effect of genotypes at the promoter and coding region mutations loci (P = 0.001) were significant for the presenting IOP of the worst affected eye. This is the first study that unequivocally shows the functional involvement of a CYP1B1 promoter variant in PCG.
Interactions between cancer and immune cells create a tumor-promoting or tumor-rejecting environment and correlate with prognosis for many cancers. The variability of immune contextures among oral squamous cell carcinoma of gingivobuccal region (OSCC-GB) patients and their relationship with prognosis are largely unknown.
Methods
In this study we estimated the immune infiltration in the tumor, surrounding surgical negative margins and adjacent normal tissues of 43 treatment naïve OSCC-GB patients, using bulk RNA-sequencing and immunohistochemistry. Prognosis of each patient was followed-up for at least two years. Immune subtypes were inferred from gene expression data. Association of patient subtypes and disease prognosis was studied.
Results
Using expressions of 544 immune related genes (IRGs) we identified a subgroup of patients with poor prognosis (high recurrences and deaths). High expression levels of three genes – CD73, ITGA3, and ITGA6 – were associated with poor overall survival and higher recurrence. Patients with good prognosis had (a) in their tumors, a high proportion of CD4+ and CD8+ T cells, B cells, NK cells, M1 macrophages, higher TCR and BCR repertoire diversity and cells positive for immune checkpoint markers, and (b) their surgical negative margins were enriched with resting memory-T and dendritic cells.
Conclusions
Better prognosis in OSCC-GB is associated with appropriate immune contextures and a subgroup, with high expression of immune checkpoint genes, may further benefit from immunotherapy.
Acknowledgements
Amrita Chaudhary2, Arnab Ghosh1, Pattatheyil Arun2, Geetashree Mukherjee2, Indu Arun 2, Arindam Maitra 1, Nidhan Biswas 1, Partha P. Majumder,1,3. 1 National Institute of Biomedical Genomics, Kalyani, India. 2 Tata Medical Centre, Kolkata, India. 3 Indian Statistical Institute, Kolkata, India.
Ethics Approval
Ethical approval was obtained from the Tata Medical Institution, Kolkata, from where patients were recuited in the study.
Consent
"Written informed consent was obtained from the patient for publication of this abstract and any accompanying images. A copy of the written consent is available for review by the Editor of this journal."
A genetic epidemiological study of serum lipid and lipoprotein levels was conducted among families of Marwaris residents in Calcutta. A total of 210 families, comprising over 100 individuals, were studied. Analyses were performed to estimate the genetic and environmental effects on the determination of high density lipoprotein cholesterol (HDL-C) and serum triglycerides (TG). Familial correlations for HDL-C and TG were estimated: parent-child and sib-sib correlations were found to be significant. Spouse correlations were not significant. Correlations between environments of siblings were significant. Genetic analysis of data on HDL-C and TG performed under a path model, taking genetic transmission and possible environmental associations among family members into account, indicated that lipid and lipoprotein levels adjusted and standardized for age, gender, education, occupation and disease status are primarily determined by genetic factors. The effects of environmental factors were also significant, although in comparison with genetic factors these effects were much smaller. The estimated genetic heritability for HDL-C was approximately 80 per cent, while that for TG was approximately 55 per cent. The genetic effects and environmental effects were not significantly different between adults and children.
Background & objectives: SARS-CoV-2 (Severe acute respiratory syndrome coronavirus-2) is evolving with the progression of the pandemic. This study was aimed to investigate the diversity and evolution of the coronavirus SARS-CoV-2 with progression of the pandemic over time and to identify similarities and differences of viral diversity and evolution across geographical regions (countries). Methods: Publicly available data on type definitions based on whole-genome sequences of the SARS-CoV-2 sampled during December and March 2020 from 3636 infected patients spread over 55 countries were collected. Phylodynamic analyses were performed and the temporal and spatial evolution of the virus was examined. Results: It was found that ( i ) temporal variation in frequencies of types of the coronavirus was significant; ancestral viruses of type O were replaced by evolved viruses belonging to type A2a; ( ii ) spatial variation was not significant; with the spread of SARS-CoV-2, the dominant virus was the A2a type virus in every geographical region; ( iii ) within a geographical region, there was significant micro-level variation in the frequencies of the different viral types, and ( iv ) the evolved coronavirus of type A2a swept rapidly across all continents. Interpretation & conclusions: SARS-CoV-2 belonging to the A2a type possesses a non-synomymous variant (D614G) that possibly eases the entry of the virus into the lung cells of the host. This may be the reason why the A2a type has an advantage to infect and survive and as a result has rapidly swept all geographical regions. Therefore, large-scale sequencing of coronavirus genomes and, as required, of host genomes should be undertaken in India to identify regional and ethnic variation in viral composition and its interaction with host genomes. Further, careful collection of clinical and immunological data of the host can provide deep learning in relation to infection and transmission of the types of coronavirus genomes.
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