MBBS Year 1 Genomics PDF

MBBS Year 1 Genomics Dr Jordana Bell Department for Twin Research & Gene c Epidemiology King’s College London [email protected] ti What is Genomics? The study of whole genomes Their sequence, structure, func on & evolu on. ti...

MBBS Year 1 Genomics Dr Jordana Bell Department for Twin Research & Gene c Epidemiology King’s College London [email protected] ti What is Genomics? The study of whole genomes Their sequence, structure, func on & evolu on. ti ti What is Genomics? The study of whole genomes Their sequence, structure, func on & evolu on. Why study Genomics in Medicine? Understand the gene c basis of biological mechanisms, human traits and diseases. Genomics in disease: Pathogenesis Risk Diagnosis Treatment Progression ti ti ti  The Human Genome: milestones Franklin, Wilkins Reproduced from Prokop et al. 2018  Genomics vs omics? Genomics: Typically refers to changes in DNA sequence at genome level Regulatory and/or func onal genomics: Typically refers to changes in the structure, packaging, and func on of DNA sequence and DNA products Omics Broad term used to describe the characterisa on and quan ca on of di erent layers of biological informa on in an organism Quan fy biological molecules, their pathways and dynamics ff ti ti ti ti ti fi ti ti Insights into molecular mechanisms - ‘omics Genome Epigenome Transcriptome Proteome Glycome Metabolome Microbiome Insights into molecular mechanisms involved Genome Epigenome Phenotype Transcriptome Disease Proteome Glycome Metabolome Microbiome  The landscape of clinical genetics is changing Genome medicine Genomic revolu on - More coverage More people More disease loci Towards personalised* medicine - treatment is tailored to the pa ent, considering their individual gene c & environmental data UK 5-year Genomics strategy into clinic Images adapted from NHGRI (genome.gov) & Boyco et al. 2013 Nat Rev Gen; *Stra ed or precision ti ti fi ti tt ti  Exci ng new milestones in genomics Cheaper & faster sequencing technologies New sequencing technologies (long read sequencing), e.g. Oxford Nanopore (ONT) & PacBio Portable genome sequencing - bedside tes ng e.g. ONT palm-sized MinION sequencer has helped track the spread of Ebola & Zika, track Tb pathogens, etc Infection Control MRC-funded researchers in Brazil use MinION for the Zika Rapid Response Initiative project Tailored treatment (e.g. adverse drug reac ons - ibuprofen; e cacy) ffi ti ti ti Ethics Many ethical issues associated with gene c research Privacy/ Iden ability, Incidental nding, Minors in gene c research, … Two key tools to ensure protec on of par cipants in clinical & research trials: Informed consent Giving su cient and appropriate informa on about the research, to allow par cipants to make a meaningful choice about whether or not to take part Ethics commi ee review Ensures that the rights of par cipants are preserved Online lecture by Prof Prainsack ffi ti ti fi tt ti fi ti ti ti ti ti  Genomics Block: Content Part 1: Introduc on to genomics What is genomics and gene c varia on; gene c varia on in human disease; ongoing large-scale sequencing projects; key research areas in popula on genomics and ‘omics and their relevance for disease Part 2: Clinical applica ons of genomics: examples & ethics Clinical gene cs, examples of genomic research in human disease, and genomics in disease therapy. Ethical implica ons of genomic research. ti ti ti ti ti ti ti ti ti Gene c Concepts going into the block Gene c terminology Gene - gene structure, chromosome, chroma n, karyotype Gene c varia on - locus, allele, genotype, haplotype, etc Related concepts - recombina on, linkage, linkage disequilibrium, heterogeneity, etc Modes of inheritance Mendel’s law, autosomal & X-linked modes of inheritance Reduced penetrance, variable expressivity, imprin ng, etc Biology Transcrip on & transla on, and their gene c & epigene c regula on Nucleus & nuclear organisa on, cell organelles, cell biology ti ti ti ti ti ti ti ti ti ti ti ti ti  Genomics KEATS page h ps://keats.kcl.ac.uk/course/view.php?id=115486 Genomics KEATS Content: Lectures - in person; lecture slides - on KEATS Workshops - in person; workshop slides - on KEATS Online ac vi es/lessons - online exercises - on KEATS LOs / prac ce ques ons / Q&A - KEATS page tt ti ti ti ti  Genomics KEATS page h ps://keats.kcl.ac.uk/course/view.php?id=115486 Genomics KEATS Content: Lectures - in person; lecture slides - on KEATS Workshops - in person; workshop slides - on KEATS Online ac vi es/lessons - online exercises - on KEATS LOs / prac ce ques ons / Q&A - KEATS page Feedback ([email protected]) tt ti ti ti ti