MSOP-1016 Genetic Medicine & Medical Tools - Dr. Fani Papagiannouli

Introduction to Genomics

• Genomics is the study of genes and their roles in inheritance, focusing on variations in genes that determine the cause of a health condition.
• The human genome contains approximately 20,000 coding genes, which are the DNA loci that "code" for a "trait".
• Chromatin is composed of DNA and histones, and chromosomes are made up of 2N (diploid) pairs, with 23 pairs of chromosomes in total, including 22 pairs of autosomes and 1 pair of sex chromosomes.

Genomic Variation

• Genomic variation reflects the differences in a person's DNA compared to other people's DNA.
• There are multiple types of variants, ranging from small differences to large differences.
• Structural chromosomal changes include deletion, duplication, inversion, insertion, and translocation variants.
• Single Nucleotide Polymorphism (SNPs) are genetic variations between individuals at individual nucleotides, with approximately 1 in 1000 bases within the human genome showing variation.

Non-Coding DNA

• Non-coding DNA (or "dark DNA") corresponds to parts of the genome that do not code for amino acids.
• Only 2% of the human genome encodes proteins, while the remaining 98% of the genome is non-coding.
• Newer studies have shown that 80% of our DNA shows some degree of activity and could have a purpose.
• Non-coding DNA sequences have known functional roles, including regulating gene expression, maintaining and protecting the structure of the genome, and directing the production of RNA molecules.

Bioinformatics

• Bioinformatics is an interdisciplinary field that develops methods and software tools for understanding biological data.
• Bioinformatics was essential to the overall success of the Human Genome Project.
• The field has established facilities for collecting, storing, organizing, interpreting, analyzing, and communicating genomic data.

The "Omics" Revolution

• The suffix "-ome" comes from the Greek for "all", "every", or "complete".
• Omics refers to the collective technologies used to characterize and quantify pools of biological molecules.
• The "omics" revolution has led to the development of various fields, including genomics, transcriptomics, proteomics, and metabolomics.

Human Genomic Variation

• Human genomic variation is the study of the differences in a person's DNA compared to other people's DNA.
• The study of human genomic variation has identified genetic variants associated with specific traits or conditions.
• Genome-wide association studies (GWAS) have identified genetic variants for diseases such as type-2 diabetes, rheumatoid arthritis, and osteoporosis.

Model Organisms and Comparative Genomics

• Model organisms are species that are studied to understand biological processes and diseases.
• Comparative genomics projects have identified many novel genes and have been of vital importance in the Human Genome Project.
• Examples of model organisms include E. coli, yeast, C. elegans, D. melanogaster, M. musculus, and R. norvegicus.

Epigenetics

• Epigenetics is the study of heritable changes in gene function that occur without a change in the underlying DNA sequence.

• Epigenetics is often referred to as "on top of" genomics because it focuses on the modifications to the genome that can affect gene expression.

• Epigenetics plays a crucial role in the development and differentiation of cells, and is essential for understanding the diversity of cells in the human body.### Epigenetics

• Epigenetics affects gene regulation without changing the DNA sequence, influencing when genes are turned on and off, and which proteins are produced.

• Epigenetics can control the structure of the genome, relaxing tightly packed chromosomes to allow factors controlling gene expression to access genes.

• Epigenetic modifications are mostly transient and reversible, but can also be inherited, enabling cells to respond and adapt to environmental and behavioral changes.

Epigenetics and Environment

• Epigenetics can be influenced by external factors, such as diet, lifestyle, and stress.
• During pregnancy, the epigenome of a developing baby can be influenced by the expectant parent's lifestyle.

Types of Epigenetic Modifications

• DNA Methylation: associated with switching genes off, by attaching a methyl group to a region near the start of a gene.
• Histone Modification: regulates gene expression through chromatin remodeling, including acetylation, methylation, and phosphorylation.
• Non-coding microRNAs (miRNA): bind and target mRNAs for degradation, leading to gene regulation.

Epigenetics and Cancer

• Nearly all cancers display different epigenetic patterns compared to typical, healthy cells.
• Epigenetic modifications, such as methylation profiles, can help grade cancer stages and track disease progression.
• Some genes produce proteins that stop cell growth and division, and epigenetic silencing of these genes can lead to cancer development.
• Epigenetic-targeting drugs are used to treat cancer, either by removing or preventing epigenetic modifications.

Genomic Imprinting

• Genomic imprinting is an epigenetic phenomenon where some epigenetic markers are passed on from parents to offspring, leading to the "parent of origin" effect.
• Imprinting occurs during gametogenesis, resulting in the silencing of either the maternal or paternal copy of a gene.
• At least 80 human genes are known to be imprinted, and the regions are known as differentially methylated regions (DMRs).

Genetics vs. Genomics

• Genetics: the study of genes and how they are inherited, focusing on variations in gene(s) to determine the cause of a health condition.
• Genomics: the study of an organism's genome, including both coding and non-coding regions, and applying this information to understand biological processes.

Human Genome Project

• The Human Genome Project was a large, international collaborative effort that generated the first sequence of the human genome.
• The project involved thousands of researchers, multiple universities, and research centers across the US, UK, France, Germany, Japan, and China.
• The project was a successful example of "big science" in biomedical research, producing a genome sequence that accounted for over 90% of the human genome.

Next-Generation Sequencing

• Next-generation sequencing technology allows for rapid and affordable whole genome sequencing.
• The technology generates a vast amount of data, with sequencing one person's whole genome amounting to around 200GB.
• Whole genome sequencing has applications in healthcare, enabling personalized medicine and disease diagnosis.

The Human Genome Project Moving Forward

• The Human Genome Project contributed to the creation of the HapMap Project and 1000 Genomes Project, which facilitated whole genome-wide association studies (GWAS).
• The 100,000 Genome Project was launched in the UK in 2012, aiming to sequence 100,000 genomes to improve disease diagnosis and treatment.

Explore the distinctions between genetics, genomics, pharmacogenetics, and pharmacogenomics in the context of medical tools and personalized medicine. Learn about genetic risk factors, epigenetics, and approaches to rare diseases.