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.