Indian Journal of Genetics and Molecular Research

Haploinsufficency (HI), wherein a single functional copy of a gene is insufficient to maintain normal function, is a major cause of dominant disease. Human disease studies have identified several hundred haploinsufficient genes affecting a range of phenotypes. In this mini-review we review the topic of HI with reference to brain and human neuropsychiatric diseases, providing clinical, genetic, and pathological implications of the mechanism. Further,the genetic implications of HI (“stuck”) genes from evolutionary and genetic lenses are reviewed along with potential clinical applications. In summary, the study of HI assumes significance since its spectrum extends to the realm of biophysics, gene expression, chromosome biology, quantitative traits, and evolutionary biology.

The majority of non-repetitive DNA in higher eukaryote genomes is transcribed, but only a small portion of them code for proteins, which appears to be a conundrum. The term "smORF-encoded proteins" (SEPs) refers to small open reading frames (smORFs) that encode functional proteins and are located across the genome in various locations, such as coding sequences (CDSs) and the 5' and 3' untranslated regions (UTRs) of genes. Numerous vital processes, such as metabolic, cellular, gene expression, embryogenesis and development are carried out by SEPs. Additionally, they are connected to a number of clinical conditions promote proteome evolution. As omics technology and identification techniques progress, a large number of peptides are currently being annotated. Further, several of these peptides are essential for the regulation of reproductive physiology and development in insects. Male seminal fluid proteins (SFPs) elicit a physiological response in the females during mating that increases the reproductive success of the mating pair. This response is known as the post-mating response (PMR). SFPs exhibit a broad distribution of relative molecular weights and influence a variety of functions, including catalysis, inhibitor activity, and protein folding and binding. It is now known that several of these proteins, such as MSAmiP in Drosophila, are crucial to insect reproduction. The area of smorf is reviewed in this mini-review, covering basic biology, mechanisms and functions, methodology and advancements finally evolutionary trends. Further expansion of the discussion to their involvement in insect reproductive physiology is also included.

Background: Beedi-rolling is a traditional occupation in India that predominantly involves women and exposes them to tobacco dust. Tobacco exposure is associated with various health risks, including disruptions in hormonal pathways critical for female fertility. Aims: This case-control study aimed to investigate the association between polymorphisms in estrogen receptor genes (ESR1 and ESR2) and the follicle-stimulating hormone receptor gene (FSHR) with female infertility in beedi-rollers. Methods: A total of 500 beedi-rollers (BR) and 500 non-beedi-rollers (NBR) of reproductive age were recruited. DNA was extracted from blood samples and genotyped for ESR1, ESR2, and FSHR polymorphisms using PCR and Sanger sequencing. Statistical Analysis: Statistical analysis was conducted using SPSS version 30, including chi-square tests for genotype distribution, odds ratios for assessing the risk of infertility, and logistic regression models to adjust for potential confounders. Results: Reproductive health problems were more prevalent among BR compared to NBR, with significantly higher incidences of infertility (p = 0.02), premature ovarian insufficiency (p < 0.001), and miscarriage (p < 0.001). Genotypic analysis revealed a significant association between ESR2 (CG/GG) and FSHR (CT/TT) polymorphisms and infertility risk among BR. Combined genotype analysis demonstrated that carriers of ESR2 (CG/GG) and FSHR (CT/TT) exhibited the highest susceptibility (p = 0.02). Conclusions: The findings highlight that prolonged exposure to tobacco dust and specific genetic predispositions contribute to infertility in beedi-rollers. This study underscores the importance of genetic screening to mitigate infertility risks in vulnerable occupational groups.