BMS656 Functional Genomics UITM Assignment Answer Malaysia 

The BMS656 Functional Genomics course at UITM (University Teknologi MARA) in Malaysia offers a comprehensive overview of genomics. It explores the fundamental concepts, methodologies, and technical advancements related to genome sequencing. The course focuses on Next Generation Sequencing, complete genome sequence determination, and the application of genome data to address biological inquiries. It aims to provide students with up-to-date knowledge on cutting-edge genomic technologies.

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Assignment Task 1 : Describe the architecture and components of the general genome structure of eukaryote and bacteria.

Eukaryotes and bacteria have distinct genome structures due to their fundamental biological differences. Let’s explore the architecture and components of their genomes:

Eukaryotic Genome Structure:

• Nuclear Genome: Eukaryotic cells have their genetic material enclosed within a membrane-bound nucleus, known as the nuclear genome.
• Linear DNA: The majority of eukaryotic genomes consist of linear DNA molecules organized into multiple chromosomes. Each chromosome contains genes, regulatory elements, and non-coding regions.
• Introns and Exons: Eukaryotic genes often contain introns (non-coding regions) and exons (coding regions). Introns are removed during RNA splicing, producing mature mRNA for protein synthesis.
• Repetitive Elements: Eukaryotic genomes can contain repetitive DNA sequences, such as transposable elements and tandem repeats, which can play essential roles in genome evolution and regulation.
• Organelle Genomes: Eukaryotic cells also possess DNA in their mitochondria and chloroplasts (in plants), which are derived from ancient symbiotic bacteria.

Bacterial Genome Structure:

• Nucleoid: Bacterial genetic material is organized in a region called the nucleoid, which lacks a membrane-bound nucleus.
• Circular DNA: Most bacteria have a single circular chromosome that contains all the genetic information necessary for their survival and reproduction.
• Operons: Bacterial genes are often organized into operons, where a cluster of genes is transcribed together as a single mRNA, regulating their expression collectively.
• Plasmids: Bacteria may also contain extra-chromosomal elements called plasmids, small circular DNA molecules that can be transferred between bacterial cells, carrying additional genes and providing adaptive advantages.

Assignment Task 2 : Describe the technology platforms and methods available for genome sequencing projects , and the objectives and challenges of the different genome projects

Technology Platforms and Methods for Genome Sequencing Projects:

• Sanger Sequencing: The first method used for DNA sequencing, based on chain-termination principles. It is not commonly used for whole-genome sequencing due to cost and labor intensiveness.
• Next-Generation Sequencing (NGS): Also known as high-throughput sequencing, NGS technologies include Illumina (SBS), Pacific Biosciences (SMRT), Oxford Nanopore (Nanopore), and others. These platforms enable faster and more cost-effective sequencing by parallelizing the process.

Objectives of Genome Sequencing Projects:

• Genome Annotation: Identifying and cataloging genes, regulatory regions, and non-coding elements.
• Comparative Genomics: Comparing genomes across different species to understand evolutionary relationships and functional elements.
• Disease Research: Studying genetic variations associated with diseases to develop personalized medicine and targeted therapies.
• Agriculture: Improving crop yield and disease resistance through understanding plant genomes.
• Environmental Studies: Analyzing the genomes of organisms in their natural habitats to understand ecosystems and environmental changes.

Challenges of Genome Sequencing Projects:

• Data Management: Dealing with vast amounts of data generated during sequencing, storage, and analysis.
• Assembly Difficulties: Piecing together short reads in the correct order for NGS data to reconstruct the complete genome.
• Repeat Sequences: Long repetitive regions in genomes can make accurate assembly and annotation challenging.
• Cost: While NGS has reduced costs significantly, whole-genome sequencing projects for large organisms or population studies can still be expensive.
• Ethical and Legal Issues: Genome sequencing raises concerns about data privacy, informed consent, and potential misuse of genetic information.

Assignment Task 3 : Explain how comparative genomics can be used in the characterization of genomes and how comparative genomics can be used to transfer genomic information from one species to another, and understand the regulation of gene expression on different levels.

Comparative Genomics in Genome Characterization: Comparative genomics involves comparing and analyzing the genomes of different species to identify similarities, differences, and evolutionary relationships. It aids in understanding genome organization, gene function, and evolution. By studying conserved regions and gene families, researchers can infer the functional importance of certain genes and predict the function of newly identified genes.

Using Comparative Genomics to Transfer Genomic Information: Comparative genomics can facilitate the transfer of genomic information from one species to another, especially when studying non-model organisms with less well-annotated genomes. By identifying orthologous genes (genes with shared ancestry and similar functions) between species, researchers can infer the function of a gene in a poorly characterized species based on the knowledge from a well-studied species.

Understanding Gene Expression Regulation on Different Levels: Comparative genomics can also shed light on gene expression regulation at various levels:

• Transcriptional Regulation: Comparing promoter regions and transcription factor binding sites can reveal how genes are regulated and controlled in different species.
• Post-Transcriptional Regulation: Studying non-coding RNAs and microRNAs can provide insights into post-transcriptional gene regulation and RNA stability.
• Epigenetic Regulation: Comparative epigenomics allows the examination of DNA methylation, histone modifications, and chromatin remodeling, influencing gene expression without altering the underlying DNA sequence.

Assignment Task 5 : Prepare and present a properly researched report on the case study and response appropriately to questions raised.

Introduction: The report aims to investigate the genetic basis of a rare genetic disorder characterized by developmental delays, intellectual disabilities, and facial dysmorphisms. This study is crucial to understand the underlying molecular mechanisms and potentially offer insights into therapeutic interventions.

Methodology:

Patient Cohort and Genetic Sequencing:

• A cohort of affected individuals was recruited, and their DNA samples were collected with appropriate consent and ethical approvals.
• Whole-exome sequencing (WES) was performed to capture and sequence coding regions of the genome.
• A control group of unaffected individuals with similar demographics was included for comparison.

Data Analysis:

Variant Calling and Filtering:

• Variants were identified from the raw sequencing data and filtered based on frequency in the general population and potential functional impact.
• Rare and novel variants were prioritized for further analysis.

Candidate Gene Identification:

• Genes containing rare or novel variants predicted to affect protein function or expression were considered as candidate genes.
• Literature review and databases were used to identify genes associated with neurodevelopmental disorders.

Functional Annotation: Bioinformatics tools were utilized to assess the potential functional impact of the identified variants on protein function and gene regulation.

Pathway and Gene Ontology Analysis: Candidate genes were subjected to pathway and gene ontology analysis to explore their involvement in relevant biological processes.

Results:

Variant Analysis: Several rare variants were identified in the affected individuals, with a significant enrichment in genes related to neuronal development and synaptic function.

Candidate Gene Identification: Gene A and Gene B were identified as strong candidate genes due to their known association with neurodevelopmental disorders and the presence of damaging variants in affected individuals.

Functional Annotation: In silico analysis predicted that the variants in Gene A could disrupt protein function, potentially affecting neurodevelopmental processes.

Pathway and Gene Ontology Analysis: Pathway analysis indicated an enrichment of genes related to neuronal development, further supporting the involvement of the identified candidate genes.

Validation:

Sanger Sequencing: Variants in Gene A and Gene B were validated using Sanger sequencing in the affected individuals and confirmed to be present.

Functional Studies:Ongoing functional experiments are being conducted to validate the impact of the variants on protein function and cellular processes.

Conclusion:The study identified potential candidate genes associated with the rare genetic disorder, shedding light on the molecular basis of the phenotype. Further validation and functional studies are warranted to elucidate the precise mechanisms and develop targeted interventions.

Presentation: Prepare slides summarizing the research report, highlighting the methodology, results, and conclusion. Use visuals and graphics to present the findings effectively. Be prepared to answer questions from the audience regarding the study design, data analysis, and implications of the research.

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