Lecture 14- Precision Medicine Flashcards
Molecular Genetics/ Biology
Molecular genetics= studies the structure + function of genes at a molecular level including their products, RNA + protein
Vocab
Gene= molecular unit of heredity made up of a sequence of nucleic acids
Genome= entire genetic material/ DNA inside an organism
Genomics= study of an organisms genome and how that information is applied; all living things have a genome; ours is made up of DNA
Chromosome; structure found within cell nucleus + a continuous length of ds DNA; in humans, 22 pairs of autosomal + 2 sex chromosomes
2 major technological breakthroughs
- 1977 Walter Gilbert + Fred Sanger
- DNA sequencing (dideoxy method) - 1983 Kary Mullis
- Method to amplify DNA
- Identified a thermostable DNA polymerase + mimics cells own DNA replication machinery to amplify DNA
PCR Applications
Cloning, DNA sequencing, forensics, quantitative PCR + human genetic/ variation
Genome projects
Slide 9
HGP; Benefits
Molecular medicine;
Genomic medicine (predict/diagnose)
Drug development (rational drug design)
Gene therapy as drug therapy
Pharmacogenomics
Forensics, microbial genomics, archaeology + agriculture + forestry
HGP; Issues
Ethical, legal + social;
- privacy + security of genetic data
- use of information; insurance
- discrimination, psychological
- clinical issues
- philosophical implications
- genetic modification
- commercialisation, patents, accessibility
- misuse and misinterpretation
Molecular Genetics
Genetic variation; difference in DNA among individuals/differences between populations among the same species
Allele; variant of the sequence of nucleotides at a particular location/gene on a DNA molecule
Gene pairs; come in pairs/ alleles in eukaryotes; each parent contributes one of the two alleles
Genotype; genetic makeup of an organism that determines/contributes to the phenotype
- can be homozygous or heterozygous
Phenotype; physical appearance/ biochemical characteristic of an organism as a result of the interaction of its genes/ environment
Allele examples
Complete dominance; allele that expresses the trait over the other trait is = dominant allele and the other one is = recessive allele - only expressed when there are 2 copies
Codominance; in some genes, the different alleles (heterozygous genotypes) are equally expressed; ABO locus- slide 18
Gene structure
2 types of DNA elements go in to the making up the gene structure;
A- Core elements- introns and exons= part of the open reading frame (ORF) + actively participate in mRNA/protein synthesis
B- Regulatory elements- promoters, enhancers and silencers = play roles in maintaining gene expression
Genetic variation
Mutation; rare
- found in <1% of population
Polymorphism; common-fixed
- mutation found in >1% of population
- give us our genetic diversity by modifying gene function
- sometimes referred to as a mutation
Types of variation;
1. Single base changes/ substitutions
2. Small insertions/ deletions
3. Variable number tandem repeats
4. Multi-gene duplication
5. Complex rearrangements
Types of mutation/ polymorphism
1- substitution/ point mutation= a mutation that changes one base for another + when common in the population is referred to as a *Single nucleotide polymorphism
^ more on slide 22
2- insertion= mutations in which extra base pairs are inserted into a new place in the DNA
3- deletion= mutations in which a section of DNA is lost/deleted
4- frameshift= protein is divided into 3bp codons, indels can alter a gene so that its message is no longer correct + usually creates truncated proteins
5- variable number tandem repeats= repeated DNA sequences at a defined locus around the genome
^ more on slide 24
SNPs
-common mutations + most frequent form of genetic variation in the genome
Distinguish individuals + populations and function as markers for pinpointing phenotypic effects through genetic association studies
Haplotype patterns= combo of SNPs along a piece of DNA
SNPs= affect how well the protein works, how it interacts with another protein/ how it is regulated = can affect how humans develop disease and respond to pathogens, vaccines + drugs
SNPs
Exons (2% of genome)- synonymous (neutral, no change in amino acid) vs non-synonymous (amino acid change)
Introns/regulatory regions- may affect gene expression, transcription, translation, RNA stability + splicing
SNP Nomeclature variation
Major (wild-type) + Minor (polymorphism/mutation) alleles - minor allele frequency that is analysed
2 copies of each gene- 1 for SNP + 2 alleles = combo of these is the genotype
Precision/ personalised medicines
Personalised= treatment/understanding of a disease is based on the sum of a patient’s individual characteristics (lifestyle, age, gender + environmental factors)
Precision= focuses on individual patients (personalised) / groups of patients (stratification) genetics when diagnosing disease, prescribing etc
Stratification= subdivides patients into groups based on their risk of developing specific diseases
Precision medicine
One size fits all; trial + error, clinically subjective -> leads to misdiagnosis, poor treatment + adverse drug reactions
Influence; effective diagnosis, impacting therapies, dosages, improving outcomes + decreasing ADRs
Genomic medicine
Subset of precision/personalised medicine + is a medical discipline that uses patient’s genomics as part of their clinical care
Genetic disorders + diseases
- caused by mutation (polymorphism)
Genetic mutations can result from;
- errors in DNA replication
- exposure to mutagens
- slide 30
Germline mutations= occurs in eggs + sperm= can be passed onto offspring while somatic mutations occur in body cells
Types of genetic disorders
- Whole chromosome are missing extra chromosomes;
- trisomy 21 (Down syndrome)
- Turner’s syndrome
- kleinfelter’s syndrome - Sections of chromosomes missing/replaced;
- Charcot-marie-tooth disease type 1- duplication
- Duchenne muscular dystrophy - deletion
- Haemophilia A - inversion
- Chronic myelogeneous leukaemia - translocation - Single gene disorders caused by genetic variants in one gene;
- sickle cell anaemia - HBB
- huntingtons disease - HD
- cystic fibrosis - Multiple gene disorder…
- Crohn’s disease
- T2D
- Heart disease
- Cancer
Genomic medicine
Pre-human genome; slide 34
Lynch syndrome
