Genetics and Epigenetics Quiz

Molecular Genetics & Genetic Disorders

• The presentation discusses the molecular basis of genetics, including gene structure, function, and expression.
• It details different types of mutations and their implications for human health.
• Diagnostic techniques used in studying genetic disorders are introduced.
• The classification and examples of genetic disorders, their molecular pathogenesis, and inheritance patterns are examined.

Activities

• The activities cover the foundation of molecular genetics, molecular diagnostics, and emerging tools.
• Activities also encompass genetic disorders, including chromosomal disorders and Mendelian inheritance.

Basic Foundation in Molecular Genetics

• The presentation includes an introduction to genetics terminology.
• DNA structure is a core concept.
• Genome and gene structure are explored.
• The central dogma of molecular biology, specifically gene expression is a significant element.
• Coding and non-coding regions within genes are differentiated.
• Mutations and their overview are presented.
• Epigenetics is discussed as a significant concept.

Key Genetic Terms & Definitions

• Genome: The complete set of genes.
• Gene: The unit of DNA responsible for protein synthesis.
• Locus: The specific site of a gene on a chromosome.
• Allele: Variant forms of a gene that might influence traits.
• Genotype: The genetic makeup of an organism.
• Phenotype: The observable characteristics resulting from genotype.
• Karyotype: A visual representation of an organism's chromosomes.

Define These Genetic Terms

• Polymorphism: The presence of different forms of a gene.
• Haploid and Diploid: Haploid cells have one set of chromosomes and diploid cells have two.
• Epigenetics: Heritable changes in gene expression independent of DNA sequence.
• Penetrance: The proportion of individuals with a specific genotype who express the associated phenotype.
• Expressivity: The variation in the intensity of a phenotype among individuals with the same genotype.
• Non-coding DNA: DNA that does not code for proteins.
• Silent Mutation: A mutation that does not alter the amino acid sequence.
• Frameshift Mutation: A mutation that alters the reading frame of the genetic code.
• Trinucleotide Repeat Expansion: A mutation involving the repeated sequences of three nucleotides.
• Gene Heterogeneity: Multiple genes can cause the same or similar phenotypes.
• Pleiotropy: One gene influences multiple traits.
• Anticipation: The increasing severity of a genetic disorder in successive generations.
• Mosaicism: Presence of two or more genetically distinct cell populations in an individual.
• Linkage Disequilibrium: Non-random association of alleles at different loci on a chromosome.
• Gene Therapy: The use of genes to treat or prevent diseases.

Structure of DNA

• DNA is a double helix.
• DNA is composed of nucleotides (adenine, thymine, guanine, cytosine).
• The specific base pairing rules for A-T and G-C govern DNA structure.

Organization of DNA

• DNA exists in heterochromatin (highly condensed, inactive) and euchromatin (loosely packed, active) forms.
• Chromatin coiling occurs through nucleosomes.

Central Dogma of Molecular Biology

• The flow of genetic information is: DNA → RNA → Protein
• Transcription converts DNA to RNA.
• Translation converts RNA to protein.
• Enzymes involved in transcription are RNA polymerases.
• Ribosomes are involved in protein synthesis.

Transcription-RNA Splicing-Translation

• DNA is unwound by RNA polymerase during transcription.
• mRNA is synthesized using a DNA template strand.
• Introns (non-coding regions) are removed, and exons (coding regions) are joined during RNA processing
• mRNA directs protein synthesis in ribosomes.
• tRNA brings corresponding amino acids.

Genetic Code

• The genetic code uses triplets of nucleotides (codons) to specify amino acids.
• The code is universal and degenerate (multiple codons for some amino acids).
• AUG is the start codon for methionine.
• UAA, UAG, UGA are stop codons.

Genome's "Dark Matter" = Non-coding Regions

• Much of the genome isn't used to produce proteins; it regulates gene expression.
• Non-coding regions are involved in architectural planning—controlling where, when, and how genes are expressed—rather than coding for proteins.
• LCRs are regions that influence a cluster of genes.

Example LCR for HBB genes

• The LCR for the HBB genes—responsible for hemoglobin—influences the transcription of multiple alpha and beta-globin genes.
• The LCR contains key regions for gene regulation.

Coding & Non-coding RNA

• RNA has both coding and non-coding roles.
• Coding RNA produces proteins (e.g., mRNA).
• Non-coding RNA regulates gene expression.
• Examples include small RNAs (e.g., miRNAs, siRNAs).

Introduction to Mutation

• Mutations are permanent alterations in DNA sequences.
• Mutations can be inherited or acquired.
• Mutations occur during DNA replication.
• External factors like radiation (chemical or UV lights) can cause mutations.
• Mutations can affect coding (exons), non-coding (introns), or regulatory regions.
• Mutations contribute to genetic diversity and many diseases.

Categories of Mutation

• Mutations can be categorized by scale (genome, chromosome, gene).
• They can also be categorized by location (germline, somatic), and effect (silent, missense, nonsense).

Where is the location of the mutation? (Germ Line vs Somatic Mutation)

• Germline mutations occur in cells that produce gametes (egg and sperm) and are inherited.
• Somatic mutations affect non-reproductive cells and are not passed to offspring.

How much is the DNA changed and lost?

• Genome mutations involve the loss or gain of whole chromosomes (monosomy, trisomy).
• Chromosomal mutations involve rearranged genetic material.
• Gene mutations involve changes in a single gene (deletion, insertion, point mutations, frameshift mutations, splicing mutations, termination mutations, trinucleotide repeat mutations).

Types of Gene Mutations

• Silent: No change in the amino acid sequence.
• Missense: Changes one amino acid.
• Nonsense: Creates a premature stop codon.
• Loss-of-function: Reduced or absent protein function.
• Gain-of-function: Enhanced protein function.

Epigenetics

• Heritable changes in gene expression without changing DNA sequences.
• Mechanisms include DNA methylation, changes to histones (proteins DNA wraps around), and non-coding RNA.

Clinical Application of Epigenetics

• Epigenetic modifications are implicated in cancer development.
• Drugs targeting methylation are used in cancer treatment.
• Epigenetic alterations influence development and can cause diseases.
• miRNA therapies target specific miRNAs.

Basic Foundation in Molecular Genetics (cont.)

• Introduction to methods for diagnosing genetic disorders.
• Concepts of karyotyping versus molecular tests.
• Molecular applications of genetic tests.
• PCR (Polymerase Chain Reaction) basic concepts and applications.
• NGS (Next Generation Sequencing) basic concepts and applications.

Method in the diagnosis of genetic disorders (cont.)

• Genetic tests are crucial for characterizing disorders.
• Tests confirm diagnosis and guide treatment.
• Genetic counseling is necessary.
• Cytogenetic analyses identify large chromosomal abnormalities.
• Molecular tests identify precise genetic changes.

Methods for Mutation Analysis

• Techniques detect large changes in chromosomes (e.g., karyotyping, FISH).
• PCR amplifies DNA fragments to detect smaller mutations.
• Southern blotting, PCR, qRT-PCR, and digital PCR are molecular tools for DNA/RNA and chromosomal analysis.
• Sanger sequencing, pyrosequencing, and next-generation sequencing (NGS) determine the order of nucleotides in DNA/RNA.
• Techniques identify specific DNA sequences (e.g., BCR-ABL1 in CML).

Karyotyping/Cytogenetic Analysis

• A technique visually maps chromosomes to detect structural abnormalities.
• Cells are prepared, chromosomes are stained, and pictures are analyzed to identify abnormalities.

Methods for DNA Analysis (past-present-future)

• Traditional methods like Southern blotting are now replaced by more advanced PCR, DNA sequencing etc.

Principle of Polymerase Chain Reaction (PCR)

• DNA is denatured, primers anneal to complementary DNA sequences, and DNA synthesis occurs.
• Specific DNA sequences are copied.
• Cycle of heating and cooling repeated to produce exponential amplification of DNA.

Sanger Sequencing/Direct Nucleotide Sequencing

• Used to determine the sequence of nucleotides in DNA.
• Primers are used to specify the sequences and ddNTPs terminate the chain synthesis to determine nucleotides.
• Capillary gel electrophoresis measures the synthesized fragments.

Next Generation Sequencing (NGS)

• Parallel sequencing to analyze multiple DNA fragments efficiently.
• Method analyzes genome's entire sequence to analyze genomic variations.

Conventional vs Real-time PCR

• Conventional PCR detects when amplification reaches a desired limit, while real-time PCR monitors amplification as it occurs.

Real-Time PCR (qRT-PCR)

• Quantifies RNA/DNA sequences in samples in real-time rather than after the process.

Evolution of DNA sequencing techniques

• The ability to rapidly sequence DNA has expanded, becoming faster and more affordable.

Test your knowledge on key concepts of genetics and epigenetics. This quiz covers topics such as mutations, gene expression, and genetic testing. Perfect for students and researchers interested in understanding the mechanics behind genetic disorders and treatments.