Lecture 30

• The Human Genome


  20,000-25,000 genes

  Only 1% of the genome

  Low gene density

  Most of the genome contains repetitive DNA and regulatory elements(enhancers or repressors)-not genes
• Genes


  Contain coding regions (exons) and non-coding regions (introns) that are involved in the production of proteins
• Non-genic regions 


  Include intergenic regions that can house regulatory elements and non-coding RNAs
• Repeats 


  Tandem repeats and interspersed repeats (transposons) that play roles in genetic variation and genome structure
• Distant Regulatory Elements


  Enhancers, silencers, and insulators that regulate gene expression from a distance, contributing to the complex control of gene activity
• Regulatory Elements: Enhancers 


  Enhances the transcription of specific genes by providing binding sites for transcription factors. They can be located from the gene they regulate
• Regulatory Elements: Silencers 


  Repress the transcription of specific genes by binding repressor proteins
• Regulatory Elements: Promoters 


  Located near the start of genes, they provide binding sites for RNA polymerase and transcription factors to initiate transcription
• Regulatory Elements: Insulators 


  Block the interaction between enhancers and promoters to prevent inappropriate gene activation
• Non-coding RNAs (ncRNAs): MicroRNAs (miRNAs) 


  Regulate gene expression by blocking the production of specific proteins
• Non-coding RNA: Long Non-coding RNAs (lncRNAs) 


  Involved in various regulatory processes in the cell
• Non-coding RNA: Small interfering RNAs (siRNAs) 


  Help in gene silencing by breaking down specific mRNA molecules
• Structural Roles


  Telomeres:

  • Protect the ends of chromosomes and prevent them from deteriorating

  Centromeres:

  • Help in the proper distribution of chromosomes during cell division
• Genomic Organisation and Chromatin Structure

  Satellite DNA:

  • Helps in organising the structure of chromosomes

  Transposable Elements (TEs):

  • Can influence gene expression and contribute to genome evolution
• Epigenetic Regulation 


  DNA Methylation:

  • Adds chemical groups to DNA that can turn genes on or off

  Histone Modification Sites:

  • Influence how tightly DNA is packaged, affecting gene expression
• Non-Functional Roles of Non-Genic DNA: Pseudogenes 


  Non-functional versions of genes that are remnants of evolution
• Non-Functional Roles of Non-Genic DNA: Vestigial Sequences 


  DNA that no longer has a function but was useful in ancestors
• Non-Functional Roles of Non-Genic DNA: Buffer Against Mutations


  Non-coding DNA can protect important genes from damage
• Non-Functional Roles of Non-Genic DNA: Spacer DNA 


  Separates different parts of the genome, helping with organisation
• Non-Functional Roles of Non-Genic DNA: Inactive (TEs)


  Past genetic elements that no longer move around but remain in the genome
• Polygenic Trait 


  These are characteristics that are influenced by multiple genes, often along with environmental factors

  Unlike single-gene (Mendelian) traits, which are controlled by a single gene, polygenic traits result from the combined effect of several genes, each contributing a small amount of the overall phenotype
• Characteristics of Polygenic Traits: Multiple Genes

  Polygenic traits are controlled by multiple genes, often located on different chromosomes
• Characteristics of Polygenic Traits: Additive Effects 


  Each gene contributes additively to the phenotype, with no single gene having a dominant effect
• Characteristics of Polygenic Traits: Continuous Variation

  These traits typically show a continuous range of variation in the population, rather than discrete categories

  This results in a bell-shaped distribution of phenotypes
• Characteristics of Polygenic Traits: Environmental Influence

  The expression of polygenic traits is often influenced by environmental factors, leading to further variation
• Examples of Polygenic Traits: Height 


  Description: Human height is influenced by the combined effects of numerous genes (possible hundreds) as well as environmental factors such as nutrition and health during childhood
• Examples of Polygenic Traits: Skin Colour 


  Skin colour in humans is determined by the amount and type of melanin produced, which is controlled by multiple genes

  Factors such as sun exposure can also affect skin colour
• Polygenic Inheritance 


  Complex traits are controlled by multiple genes, with each gene contributing to a small portion of the phenotype 

  Thes genes often interact with each other and with environmental factors, leading to the wide range of phenotypic variation observed in complex traits 
• Gene-Gene Interactions


  Epistasis: Interaction between different genes, where the effect of one gene depends on the presence of alleles at another gene 

  Additive Effects: Each gene contributes additively to the phenotype, with no single gene having a dominant effect 
• Gene-Environment Interactions


  Environmental factors such as diet, lifestyle, and exposure to toxins can influence the expression of genes involved in complex traits

  Genes and environment can interact in complex ways, leading to different phenotypic outcomes in different individuals 
• Clinical Complexity 


  Most medical disorders involve many genes and many mutations Diabetes, heart disease, stroke 

  Rare and common nutation 

  Strong and weak predictive effects 
• Systems Biology 


  Proteins made from genes interact in complex ways 

  Phenotypes are the outcome of networks on interacting proteins 
• Gene-Environment Interactions


  Height has high 'heritability' (70-80%) 

  Height changes over time, but genes do not change that fast 

  Height heavily influenced by environment (poverty/income) 
• Human individuality 


  Genes affect more than just our physical appearance 

  They (partially) drive how we act 

  Complex interplay between genes and environment