Genomics

• Briefly outline the difference between genetics and genomics.

  Genetics is the study of individual genes and their roles in inheritance, while genomics is the study of an organism's entire genome, including interactions among genes and their environments.
• Describe the relationship between the genetic code and protein structure.

  The genetic code consists of nucleotide triplets (codons) in DNA and RNA that determine the sequence of amino acids in a protein. The sequence of these amino acids dictates the protein's structure and function.
• Describe the way in which genes are encoded using the three-letter codon.

  Genes are encoded in DNA by sequences of three nucleotide bases (codons). Each codon specifies a particular amino acid that is added to a growing polypeptide chain during protein synthesis.
• Briefly outline the structure of DNA and list the bases, pyrimidines and purines, that interact as base pairs.

  DNA is a double helix with two strands composed of nucleotides. The bases are adenine (A), thymine (T), guanine (G), and cytosine (C). Purines (A, G) pair with pyrimidines (T, C): A with T, and G with C.
• Define the terms gene and pseudogene.

  A gene is a DNA sequence that contains the instructions for making a specific protein. A pseudogene is a DNA sequence similar to a gene but non-functional due to mutations.
• Describe the structure of the human genome including details of the currently accepted number of genes, regulatory RNAs and pseudogenes.

  The human genome has approximately 20,000-25,000 genes, numerous regulatory RNAs (e.g., miRNAs, lncRNAs), and around 12,000 pseudogenes.
• Describe the difference between the technical meanings of the words ‘mutant’ and ‘variant’.

  'Mutant' refers to an organism or gene that has undergone a change or mutation, typically implying an abnormality. 'Variant' refers to any change in the DNA sequence, without necessarily implying a negative effect.
• Briefly outline the main categories of genetic variant.

  Main categories include:

  • Single nucleotide variants (SNVs)
  • Insertions and deletions (indels)
  • Structural variants (SVs)
  • Copy number variants (CNVs)
• Outline the major mechanisms observed in the generation of genetic variants (mutants) including sense and non-sense single nucleotide variants (polymorphisms).

  Genetic variants arise through:

  • Sense SNVs: Change in a single nucleotide that does not affect protein function.
  • Nonsense SNVs: Change that introduces a premature stop codon.
• Outline the major mechanisms observed in the generation of genetic variants (mutants) including frame-shift variants, indels, structural variants and copy number variants.

  • Frame-shift variants: Insertions or deletions altering the reading frame.
  • Indels: Insertions or deletions of small DNA sequences.
  • Structural variants: Large alterations like inversions, translocations.
  • Copy number variants: Changes in the number of copies of a DNA segment.
• Briefly describe the major causes of gene mutation.

  Major causes include:

  • Spontaneous mutations: Errors during DNA replication.
  • Environmental factors: Radiation, chemicals.
  • Biological processes: Viral insertions, oxidative stress.
• Describe how epigenetics can affect the expression of coding genes within the genome.

  Epigenetics involves modifications like DNA methylation and histone modification that alter gene expression without changing the DNA sequence, potentially turning genes on or off.
• Briefly outline how a blood test for a monogenetic disorder is set-up using PCR.

  A blood sample is collected, DNA is extracted, and specific gene regions are amplified using PCR. The PCR products are then analyzed for mutations associated with the disorder.
• Describe the term ‘genome bioinformatics.

  Genome bioinformatics is the application of computational tools to analyze and interpret biological data, particularly genomic sequences, to understand genome structure and function.
• Outline some of the main goals of healthcare genomics.

  Goals include:

  • Disease prevention: Identifying genetic risk factors.
  • Personalized treatment: Tailoring therapies based on genetic profiles.
  • Early diagnosis: Detecting genetic conditions early.
  • Improved drug development: Understanding genetic contributions to drug responses.
• Describe the principles of Pharmacogenomics, Patient Stratification, and Personalized Medicine.

  • Pharmacogenomics: Studies how genes affect drug response.
  • Patient Stratification: Categorizes patients based on genetic profiles to predict treatment outcomes.
  • Personalized Medicine: Customizes healthcare based on individual genetic information for optimal treatment.
• Define the term ‘epigenetics’.

  Epigenetics is the study of heritable changes in gene expression that do not involve changes to the underlying DNA sequence, such as DNA methylation and histone modification.
• Describe how epigenetics can affect the expression of coding genes within the genome.

  Epigenetic mechanisms can activate or silence genes by altering chromatin structure, thereby affecting accessibility of transcription machinery and regulating gene expression patterns.
• (ExT) What are the major components of the genetic code?

  The genetic code consists of nucleotide triplets called codons, where each codon corresponds to a specific amino acid or a stop signal during protein synthesis.
• (ExT) How do nucleotide bases pair in DNA?

  In DNA, adenine (A) pairs with thymine (T) via two hydrogen bonds, and guanine (G) pairs with cytosine (C) via three hydrogen bonds. Purines (A, G) pair with pyrimidines (T, C).
• (ExT) What is the significance of the three-letter codon system in gene encoding?

  The three-letter codon system ensures that the genetic code is read correctly, with each codon specifying one amino acid, thus enabling the accurate synthesis of proteins.
• (ExT) What is a pseudogene, and how does it differ from a functional gene?

  A pseudogene is a non-functional segment of DNA that resembles a gene but has lost its protein-coding ability due to mutations. Unlike functional genes, pseudogenes do not produce functional proteins.
• (ExT) Describe the currently accepted structure of the human genome.

  The human genome contains about 20,000-25,000 genes, a vast array of regulatory RNAs (e.g., microRNAs, long non-coding RNAs), and around 12,000 pseudogenes. It is organized into 23 pairs of chromosomes.
• (ExT) How do genetic variants affect gene function and phenotype?

  Genetic variants can alter gene function by changing the amino acid sequence, disrupting regulatory elements, or affecting splicing, which can lead to variations in phenotype and susceptibility to diseases.
• (ExT) What are sense and nonsense single nucleotide variants (SNVs)?

  Sense SNVs result in a codon change that does not affect the amino acid sequence (silent mutation), while nonsense SNVs introduce a premature stop codon, truncating the protein.
• (ExT) What are frame-shift variants, and how do they impact protein synthesis?

  Frame-shift variants are insertions or deletions of nucleotides that shift the reading frame of the genetic code, leading to the production of an altered and often nonfunctional protein.
• (ExT) Define indels and structural variants.

  Indels are small insertions or deletions of nucleotides in the genome. Structural variants are larger genomic alterations, such as inversions, translocations, or large deletions/insertions.
• (ExT) What are copy number variants (CNVs)?

  CNVs are alterations in the number of copies of a particular DNA segment, which can lead to changes in gene dosage and affect gene expression and phenotype.
• (ExT) What are some common causes of gene mutations?

  Gene mutations can be caused by spontaneous errors during DNA replication, exposure to environmental mutagens (e.g., radiation, chemicals), and biological factors like viral insertions.
• (ExT) How does DNA methylation influence gene expression?

  DNA methylation typically suppresses gene expression by adding methyl groups to cytosine bases in DNA, leading to a condensed chromatin structure that is less accessible to transcription factors.
• (ExT) What is the role of histone modification in gene expression?

  Histone modifications, such as acetylation, methylation, and phosphorylation, alter the chromatin structure, making DNA more or less accessible for transcription and thereby regulating gene expression
• (ExT) How does PCR work in diagnosing a monogenetic disorder?

  PCR amplifies specific DNA regions from a blood sample, allowing detection of mutations associated with monogenetic disorders. The amplified DNA is then analyzed using techniques like gel electrophoresis or sequencing.
• (ExT) What is the focus of genome bioinformatics?

  Genome bioinformatics focuses on the development and application of computational tools to analyze and interpret genomic data, aiding in understanding genome function and identifying genetic variations.
• (ExT) What are the main goals of healthcare genomics?

  The goals include improving disease prevention through genetic risk assessment, enhancing diagnosis and treatment of genetic disorders, and developing personalized medicine approaches based on individual genetic profiles.
• (ExT) Explain Pharmacogenomics, Patient Stratification, and Personalized Medicine.

  • Pharmacogenomics studies how genetic variations affect drug response.
  • Patient Stratification categorizes patients based on genetic profiles for targeted treatment.
  • Personalized Medicine tailors medical treatment to individual genetic profiles for optimal outcomes.
• (ExT) How do environmental factors contribute to gene mutations?

  Environmental factors like UV radiation, chemical mutagens, and pollutants can cause DNA damage, leading to mutations that may result in genetic disorders or contribute to cancer development.
• (ExT) What are regulatory RNAs, and what role do they play in the genome?


  Regulatory RNAs, such as microRNAs and long non-coding RNAs, play crucial roles in gene expression regulation by interacting with mRNA, influencing its stability, translation, or splicing.
• • Pharmacogenomics: Studies how genes affect drug response.
• • Patient Stratification: Categorizes patients based on genetic profiles to predict treatment outcomes.