Influence of Polymorphism on the NFkB1 Gene (rs28362491) on the Susceptibility to Sarcopenia in the Elderly of the Brazilian Amazon

Background: Sarcopenia is a disease characterized by progressive reduction in muscle mass and strength or function. Although it is known that sarcopenia may be associated with environmental factors, studies suggest the identification of genes related to skeletal muscle maintenance that explain the susceptibility to the disease. Objective: To analyze the influence of NFkB1 gene polymorphism on susceptibility to sarcopenia in the elderly. Methods: This is a case-control study, which included 219 elderly people, 74 elderly people with sarcopenia, and 145 without sarcopenia. Samples were analyzed for NFkB1 gene polymorphism (rs28362491), genotyped in PCR, and followed by fragment analysis. To avoid misinterpretation due to population substructure, we applied a previously developed set of 61 informative ancestral markers that were genotyped by multiplex PCR. We used logistic regression to identify differences in genotypic frequencies between elderly people with and without sarcopenia. Results: It was observed that the NFkB1 gene polymorphism presented frequencies of 24%, 50%, and 26% for the genotype DEL/DEL, DEL/INS, and INS/INS, respectively. Furthermore, elderly individuals with the INS/INS genotype had increased chances (p = 0.010; OR:2.943; 95%CI:1.301–6.654) for the development of sarcopenia. Conclusion: The INDEL polymorphism of the NFkB1 gene (rs28362491) may influence the susceptibility to sarcopenia in the elderly in elderly people in the Amazon.

A non-coding indel polymorphism in the fruitless gene of Drosophila melanogaster exhibits antagonistically pleiotropic fitness effects

The amount of genetic variation for fitness within populations tends to exceed that expected under mutation–selection–drift balance. Several mechanisms have been proposed to actively maintain polymorphism and account for this discrepancy, including antagonistic pleiotropy (AP), where allelic variants have opposing effects on different components of fitness. Here, we identify a non-coding indel polymorphism in the fruitless gene of Drosophila melanogaster and measure survival and reproductive components of fitness in males and females of replicate lines carrying each respective allele. Expressing the fruitless region in a hemizygous state reveals a pattern of AP, with one allele generating greater reproductive fitness and the other conferring greater survival to adulthood. Different fitness effects were observed in an alternative genetic background, which may reflect dominance reversal and/or epistasis. Our findings link sequence-level variation at a single locus with complex effects on a range of fitness components, thus helping to explain the maintenance of genetic variation for fitness. Transcription factors, such as fruitless , may be prime candidates for targets of balancing selection since they interact with multiple target loci and their associated phenotypic effects.

A non-coding indel polymorphism in the fruitless gene of Drosophila melanogaster exhibits antagonistically pleiotropic fitness effects

The amount of genetic variation for fitness within populations tends to exceed that expected under mutation-selection-drift balance. Several mechanisms have been proposed to actively maintain polymorphism and account for this discrepancy, including antagonistic pleiotropy (AP), where allelic variants have opposing effects on different components of fitness. Here we identify a non-coding indel polymorphism in the fruitless gene of Drosophila melanogaster and measure survival and reproductive components of fitness in males and females of replicate lines carrying one or the other allele. Expressing the fruitless region in a hemizygous state we observe a pattern of AP, with one allele resulting in greater reproductive fitness while the other confers greater survival to adulthood. Different fitness effects were observed in an alternative genetic background, suggesting widespread epistatic effects. Our findings link sequence-level variation at a single locus with complex effects on a range of fitness components, thus helping to explain the maintenance of genetic variation for fitness. Transcription factors, such as fruitless, may be prime candidates for targets of balancing selection since they interact with multiple target loci and their associated phenotypic effects.

The 40bp Indel Polymorphism rs150550023 in the MDM2 Promoter is Associated with Intriguing Shifts in Gene Expression in the p53-MDM2 Regulatory Hub

Most low-penetrance genetic risk factors for cancer are located in noncoding regions, presumably altering the regulation of neighboring genes. The poorly characterized Indel polymorphism rs150550023 (rs3730485; del1518) in the promoter of MDM2 (human homolog of mouse double minute 2) is a biologically plausible candidate genetic risk factor, which might influence the expression of MDM2, a key negative regulator of the central tumor suppressor p53. Here, we genotyped rs150550023 in a Central European hospital-based case–control study of 407 breast cancer patients and 254 female controls. mRNA levels of MDM2, p53, and the p53 target genes p21, BAX, and PERP were quantified with qRT-PCR, and p53 protein was assessed with immune histochemistry in ≈100 primary breast tumors with ascertained rs150550023 genotype. We found no evidence for an association of rs150550023 with the risk, age at onset, or prognosis of breast cancer. A possible synergism was observed with SNP309 in promoter P2 of MDM2. Mean mRNA levels of MDM2, p53, p21, and BAX were ≈1.5–3 fold elevated in TP53 wildtype tumors with the minor homozygous Del/Del genotype. However, systematic shifts in p53 protein levels or mutation rates were not observed, suggesting that the elevated p53 mRNA levels are due to regulatory feedback loops that compensate for the effects of rs150550023 on MDM2 expression.

Identification of 24bp indel(s) Polymorphism in the Promoter Region of prolactin Gene and its Association with Broodiness in Tellicherry Native Chicken

Background: Broodiness is a sex linked behavioural trait observed in most of the domestic fowls and it’s also known as incubation behaviour. Prolactin (PRL) is the principal gene which plays a crucial role to the onset and maintenance of broodiness in birds. The present study was aimed at identification of 24bp (insertion-deletion) indel polymorphism at the promoter region of prolactin gene and its association with broodiness in Telllicherry native chicken population. Methods: A total number of 200 birds of Tellicherry native chicken were randomly selected from All India Co-ordinated Research Project (AICRP) on poultry improvement, Mannuthy, Thrissur, Kerala. Blood samples were collected from the wing vein under aseptic condition and isolation of Genomic DNA was done. Isolated DNA samples were subjected to polymerase chain reaction (PCR) using specific set of forward and reverse primer to detect a 24bp indel polymorphism in the prolactin gene. PCR amplicons were subjected to further molecular analysis. Result: According to the polymorphic patterns birds were categorized to three different genotypes viz., II (insertion-insertion), ID (insertion-deletion) and DD (deletion-deletion). The genotype and allele frequency was calculated and the frequency of I allele (0.6975) was found to be higher than D allele (0.3025). Results of this study suggest that the incubation behaviour could be eliminated in Tellicherry native chicken population by increasing the frequency of I allele upon selective breeding which may enhance the egg production. Therefore, this 24bp indel polymorphism could be used as a molecular marker in poultry breeding.