Population Variation and Analysis of MicroRNA Expression Assessment Answer

Chapter 1: Introduction 

Molecules essential for the regulation of gene expression are characterized as microRNAs (miRNAs) are small non-coding RNAs and are of nearly 25 nucleotides in length (Lu and Rothenberg 2018). They can regulate the expression of genes (Kelley et al. 2020). They are transcribed by DNA into primary miRNAs from there into precursor miRNAs and then into mature ones (Villegas-Miron et al. 2022). Once the mature miRNA is attained it travels from the nucleus to the cytoplasm and is incorporated into the RNA-induced silencing complex (RISC). These are involved in a variety of biological processes. They play an essential role as biomarkers (Veryaskina et al. 2022). Gene expressions refer to the identification of the gene pattern expressed during the transcription processes. The basic function of the expression studies is to detect and quantify the messenger RNA (Segundo-Val and Sanz-Lozano 2016). The analysis via the employment of miRNA is essential as they can be used for varied purposes such as biomarkers, as reporters of drug resistance, and in the making of therapeutics (Tribolet et al. 2020). The analysis of the gene expression can be carried out via the usage of the sequencing techniques such as next-generation sequencing (Zhang et al. 2019). The expression levels of miRNAs can vary significantly between individuals and populations, which has led to extensive research into the analysis of miRNA expression in different population groups. Variation in miRNA expression has been linked to a plethora of diseases, including cancer, cardiovascular disease, and neurological disorders. Understanding the variation in miRNA expression between populations with different ancestries can provide insights into the genetic and non-genetic factors that contribute to disease risk. In the case of populations with European or South Asian ancestry, several studies have investigated miRNA expression patterns using microarray or RNA sequencing technologies. In this literature review, the focus will be on the variation and analysis of miRNA expression in populations with European or South Asian ancestry.

Chapter 2: Aims and Objectives

The literature review aims to assess the variation in miRNA expression amongst the European and South Asian populations. To attain insights into the progression of various diseases and identification of the difference from the reference genome.

The establishment of systemic reviews requires the usage of the research question. It is essential to develop a research topic that can help gather the data required for the literature review. The research question gives an idea concerning what the study aims at achieving and what is the basic idea or goal of the current research.

• Analyze the variation in miRNA gene expression that exists between the European or South Asian ancestry

Chapter 4: Methodology

The literature review is one of the types of research methodology that will be done for this topic.

This form of writing assist in evaluating all the evidence presented in a way to generate a research question effectively ( Paré and Kitsiou 2017). It is a method for conducting a methodical and transparent review of the literature that identifies, selects, and evaluates all pertinent research studies. The status of knowledge about a specific topic is extensively described methodically. A literature review is a type of review that is based on grasping and collecting the maximum amount of information available on a particular topic (Kraus et al. 2022).

 It is a method for conducting a methodical and transparent review of the literature that identifies, selects, and evaluates all pertinent research studies (Leite et al. 2019). The status of knowledge about a specific topic is extensively described methodically. It is viewed as one of the most standardized and sturdy methods to provide accurate data concerning a particular topic.

The advantage of the literature review is to aid the researchers with high-end information and in-depth knowledge about the topic of interest. Reviewing and critiquing are the essential components of the systemic literature review (Chigbu et al. 2022). Different steps of the literature review are employed in the present review.

Identification of inclusion and exclusion criteria is critical in research and it determines the quality of the research conducted (Frampton et al. 2017). It is possible to establish an inclusion and exclusion basis to ensure that only pertinent items are pulled from databases. The primary characteristics of the target sample that are exploited by the researchers of the study to meet the purpose of the research are referred to as inclusion criteria (Patino and Ferreira 2018). The characterized that are perceived as inclusion traits but lacks to fall in this dimension due to the existence of extra traits that may limit the scope of the study are referred to as exclusion traits (Su et al. 2023). The inclusion criteria include only those articles that are published from 2017 to 2023. Preferred language can also be a kind of inclusion criterion. For example for the scope of the current study English language is preferred. Qualitative studies are best suited for the writing of the literature review. 

Search Strategy : The Boolean retrieval model generates a query in the form of a Boolean expression of terms seeking information (Bramer et al. 2018). In other words, the operators AND, OR, and NOT are used to combine phrases. Each document is merely a collection of words in the model's eyes (Aliyu 2017).

Quality Assessment and Ethical Consideration: CASP tool is employed for critically appraising the review article. This tool aids in assessing the quality of the research along with determining the validity of the research finding (Pietilä 2020). Maintaining confidentiality and acquiring informed consent are the key principles of doing research ethically. In the present study, ethical issues have been given importance. In the present study, the proper credit will be allowed to the original authors by giving in-text citations along with providing the references for the same.

Chapter 4: Literature Review

The study presented by Guo et al. 2021 describes the miRNA expression in the human placenta and associated links with the population identity and the newborn's gender. For the scope of the study, the researchers employed high-throughput RNA sequencing to analyze and comprehend the miRNA expression profiles. For the study, the researchers used placenta samples from distinct populations such as African Americans, European Americans, South Asians, and East Asians as prescribed in the previous study (Hughes et al. 2015). The sample size was 36 and was obtained from the mothers of newly born males and females. The researchers aimed to examine both the individual and combined effects of population identity and newborn sex on miRNA expression. After the sequencing, the researchers yielded a total of 938 annotated and 70 novel miRNA transcripts that were expressed in the placenta. Out of this 9% of the annotates and 16% of the novel miRNAs displayed differences in their expression amongst diverse ethnic ancestry. After the population-based differences, the sex of the newborn was the facilitator of the variation in the genetic expression. The authors conducted further analysis on the 139 miRNAs that showed expression differences associated with population identity. The analysis revealed that 93 out of these 139 miRNAs exhibited significant expression differences between at least one pair of populations. Statistical tests such as student t-test along with p-values were used to determine the significance. The employment of a limited sample size could limit the scope of the present study. Whereas the approach to study both the influence of the population identifies as well as the gender of the newborn on miRNA expression in the placenta. The study provides a more comprehensive understanding of how these factors contribute to miRNA expression variations. They visualized that the population identity is significant in determining the difference in the miRNA expression variation amongst the diverse population. The environmental and social differences that may exist between diverse ancestral groups can also contribute to the development of the variation amongst the miRNA expression.

The research conducted by Warren et al. 2017 aims at studying the genome-wide association analysis and is employed to comprehend and identify the blood pressure (BP) loci associated with cardiovascular risk. The researchers aim at identifying the genetic loci that are associated with the occurrence of blood pressure. The sample size of the present study is European, South Asian, East Asian, and African ancestry. A total of 340,000 individuals were selected as the sample size and were retrieved from the population-based and case-control studies. Genotyping and imputation techniques were employed for the miRNA analysis. The genome-wide analysis was performed which assisted in comprehending the association amongst millions of genetic variants such as miRNA genes and the blood pressure traits such as systolic and diastolic BP. The researchers found a minimum of 34 novel loci that are related to BP. These loci were novel and had not been previously associated with BP regulation, depicting new potential targets. The researchers also found differences in genetic variants associated with blood pressure based on diverse ethnic ancestry. The study found an association of certain genetic loci and that was restricted to only a particular ethnic population. One of the major drawbacks that could limit the scope of the study is that they combined data from various cohorts, resulting in variations in sample sizes and study designs. The differences in sample sizes among ethnic groups could affect statistical power and the ability to detect ethnic-specific genetic associations accurately. Although there was a predominant representation of individuals of European ancestry, the study included participants from diverse ethnic backgrounds, such as South Asian, East Asian, and African ancestry. This diversity enables the exploration of genetic associations and variations across different populations. They identified loci that were associated with atherosclerosis and vascular re-modelling. In totality they provided novel 107 loci that were associated with BP, providing greater insights into the therapeutic targets and providing the details to produce medicinal alternatives to mitigate the risk of hypertension and hence cardiovascular risk.

The study conducted by Gong et al. 2019 aims at adding to this notion that miRNA expression not only arises due to cancer subtypes but also due to the differences in ancestry. The authors tried to analyze the variation in the miRNA expression of the breast cancer tissues obtained from the different ancestry of Europe and its comparison with that of Africa. It is hypothesized that American women of African ancestry are more susceptible to developing breast cancer as compared to that of European origin due to the overexpression of estrogen-negative receptors (ER-). To analyze this, the researchers employed high-throughput genome expression studies. The sample population employed for the present study was a total of 58 participants (29 African American and 29 European American). The next-generation sequencing was employed to analyze the differences in miRNA gene expression. The R package DESeq2 was employed to identify the differences in the miRNA expression of the different groups. Several differentially expressed miRNA, DEmiRs were distinct in different races with limited if 23 DEmiRs present in the tumour samples of both the ancestral groups naming miR-934, miR-9-3p/5p, miR-135b and miR-190b. Similar results were are descripted by Loh et al. 2019. The results indicate that distinct and unique subsets are present differentially in the ER- and ER-positive tumors in both the distinct ancestry referring to the distinction in the heterogeneity of breast cancer between the above-mentioned two ethnic groups.

The study conducted by Tripathi et al. 2022 aimed at comprehending the variation at the miRNA levels by employing next-generation sequencing techniques. For this study, peripheral blood mononuclear cells (PBMC) of the patients having breast cancer of South Indian origin were taken. The women were divided into three distinct age groups. Results of the study showed variation existed between the cancer patients and same-age healthy patients. Four distinct miRNAs such as hsa-miR-192-5p, hsa-miR-24-2-2p, hsa-miR-3609, and hsa-miR-664b-3p differ in expression. Hence these can act as potential biomarkers for the analysis of distinct diseases such as breast cancer. The limitation that could restrict the scope of this study can be the usage of a small sample size.

The research presented by Rotival et al. 2020 focuses on the establishment of the differences in the miRNA expression that contributed to the variation in diverse ancestry. For the scope of the present paper, they studied the miRNA gene expression variation that exists between the European and African ancestry and how these variations impact the prevalence of poor immune response. For this purpose, they used the primary human monocytes of the members of both the ancestry followed by the immune activation either via the usage of the TLR route or through the infection with the influenza virus. Genotyping and imputation procedures were adopted in the current research to analyze the expression of miRNA and its variation. The sample size of the study was 200 individuals, equally from both lineages. A total of 977 sequencing profiles were generated from the sample population. The final yield set was nearing about 736 loci with 658 distinct miRNAs loci visualized between the two ancestries. The immune activation in turn results in the modification of miRNA. The difference in both populations was stated due to the non-genetic factors. A total of 351 miRNA profiles were identified that differed amongst the population. The most common modification observed was in the 3′-end shortening of miRNAs located on the 3p arm and often observed in the African ancestry. The study tried to examine the genetic and non-genetic factors that are associated with presenting the variations that exist amongst the population about miRNA expression. Analyzing such differences assist in responding to viral or bacterial infections more effectively. 

Relation to the proposed research proposal: The identification of the variation at the level of miRNA expression level assist in comprehending the relationships that exist among this variation and helps in the development of a new human genome including these variations. By examining variations at the level of gene expression amongst diverse races of the human population i.e. European or South Asian ancestry, it can be demonstrated that over time miRNA has stabilized the expression of a small number of target genes. The genes regulated by miRNA show higher variations (Liu and Shomron 2022). Comprehending these variations assists in achieving a comprehension of the novel expressions of the human genome as these variations were not present initially. As a result, these variations can act as novel biomarkers that can assist in the regulation of disease control and provides an approach toward novel therapeutic options (Condrat et al. 2020).

Chapter 5: Conclusion

After critically analyzing the studies, it can be visualized that there exists strong relation between the population variation and the differences in the miRNA transcriptional profiles. Establishing the variation in miRNA expression between populations with distinct ancestries can assist in providing great insights into the genetic and the non-genetic factors that contribute to the risk of the development of disease. In the scenario of European and South Asian ancestry, many genetic and environmental factors have played a role in the development of the variations at the expression levels. Each population has different characteristics that can account for these differences. The expression of various receptors can exist amongst different ethnic groups which makes them more or less susceptible to developing a particular condition. And comprehending these differences can aid researchers all around the world to come up with novel therapeutic alternatives to approach these distinctive variations which are unique for each ethnicity. Distinct techniques can be used for the analysis of the miRNA expression, such as next-generation sequencing, Nano string technology, qRT-PCR, etc. Variation in miRNA expression has been linked to a variety of diseases, including cancer, cardiovascular disease, and neurological disorders.

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