Genes 1 structure of the chromosome, revision patterns of inheritance - Dr Charlotte Illsely (2024-25).pptx

Genes 1: Structure of the chromosome and patterns of inheritance Year 2 Charlotte Illsley [email protected] PSQ C505 Learning objectives By the end of this session, you should be able to: Revise and revisit core is...

Genes 1: Structure of the chromosome and patterns of inheritance Year 2 Charlotte Illsley [email protected] PSQ C505 Learning objectives By the end of this session, you should be able to: Revise and revisit core issues in genetics covered at a pre-university level; nucleotide bases>codons>genes>DNA>RNA Revise and revisit core Mendelian genetics, autosomal/x-linked, dominant/recessive patterns of inheritance covered at a pre-university level Introduce the theme of complex patterns of inheritance Define mutation and explain the terms inherited and somatic mutations Introduce the concept of genetic vs epigenetic effects and their significance We will look more at genes to proteins and at genetic diseases in Genes 2 and 3 Why learn about genetics in dentistry? Why learn about genetics in dentistry? Basic structure of DNA Deoxyribonucleic acid (DNA) ribonucleic acid (RNA) DNA is composed of ‘bases’ = nucleotides These pair up specifically – do you remember how? (DNA only) (RNA only) https://ib.bioninja.com.au/standard-level/topic-2-molecular-biology/26-structure-of-dna-and-rna/nitrogenous-bases.html  Basic structure of DNA The bases pair up with 2 or 3 hydrogen bonds The double helix is formed from the bases and the phosphate deoxyribose backbone The strands run in opposite directions When we write down a DNA sequence it’s always the coding strand and goes 5’ to 3’ https://courses.lumenlearning.com/wm-biology1/chapter/reading-structure- of-dna/  Genetics core concepts DNA is a code and a specific section of DNA makes a gene Transcription of DNA by the enzyme RNA polymerase (U instead of T) into RNA Translation of RNA at the ribosome into proteins https://www.khanacademy.org/science/biology/gene-expression- https://genius.com/Biology-genius-the-central-dogma- central-dogma/transcription-of-dna-into-rna/a/overview-of- annotated Transcription DNA is a code and a specific section of DNA makes a gene Transcription by the enzyme RNA polymerase (U instead of T) https://www.khanacademy.org/science/biology/gene-expression-central-dogma/transcription-of-dna-into-rna/a/ Translation RNA is then read in codons, with each codon (3 bases) encoding a single amino acid This process is translation and happens at the ribosome We will look more at this in the next https://www.genome.gov/genetics-glossary/Ribosome session - Genes 2 The Geneti c Code By Edited by Seth Miller User:arapacana, Original file designed and produced by: Kosi Gramatikoff User:Kosigrim, courtesy of Abgent, also available in print (commercial offset one-page: original version of the image) by Abgent - Original file: en:File:GeneticCode21.svg, Public Domain, https://commons.wikimedia.org/w/index.php? curid=4574024  By Edited by Seth Miller User:arapacana, Original file designed and produced by: Kosi Gramatikoff User:Kosigrim, courtesy of Abgent, also available in print (commercial offset one-page: original version of the image) by Abgent - Original file: en:File:GeneticCode21.svg, Public Domain, https://commons.wikimedia.org/w/index.php? curid=4574024 https://commons.wikimedia.org/w/index.php?curid=4574024 Recap The genetic code is made of a string of DNA letters (ATCG) This is converted into a string of RNA letters (AUCG) Triplets of bases (codons) code https://www.genome.gov/genetics-glossary/Chromosome for single amino acids One amino acid can be coded for by more than one codon There is redundancy in the code  Genome Genome = entire set of DNA instructions found in a cell Our whole genome is stored in chromosomes in the nuclei of all of our cells (not RBCs) Different genes are expressed in different cells and tissue types (we’ll do more on this later this year) https://www.genome.gov/genetics-glossar Genomics education programme Genetic inheritance Types of genetic inheritance: Monogenic inheritance is an inheritance pattern which determines a particular trait by one set of alleles or a specific gene (Mendelian inheritance) Polygenic inheritance determines a particular trait by more than one gene (non-Mendelian). These traits (e.g. skin colour) show continuous variation Multifactorial/complex traits are influenced by more than one gene plus environmental factors (e.g. height)  Genetic inheritance - monogenic Inheritance of a trait through one gene is monogenic inheritance Mono = one Mendelian inheritance generally describes simple inheritance where one gene is involved (and two alleles) First described by Gregor By Unknown - http://0.tqn.com/d/biology/1/0/l/e/3 Mendel who experimented 244238.jpg, Public Domain, https://commons.wikimedia.org/w/i on pea plants By Aftabbanoori - Own work, CC ndex.php?curid=33347279 BY-SA 3.0, https://commons.wikimedia.org/w/i ndex.php?curid=31378172 Mendel and his peas By Aftabbanoori - Own work, CC BY-SA 3.0, https://www.khanacademy.org/science/biology/classical-genetics/mendelian--genetics/a/mendel-and-his-peas? https://commons.wikimedia.org/w/i modal=1 ndex.php?curid=31378172  Genetic inheritance - terms Genotype Describes the genetic information (e.g. HH or Hh in this case) Phenotype How this manifests (e.g. flower colour) https://www.genome.gov/genetics-glossary/Allele Alleles Alternative forms of the same gene found at the same place on a chromosome (two or more) Homozygous Having two of the same alleles Heterozygous Having two different alleles https://www.genome.gov/genetics-glossary/Karyotype Genetic inheritance - monogenic Autosomal traits are carried on any chromosome other than X and Y (sex chromosomes) Can be dominant or recessive we’ll look at what this means in the punnet square on the next slide Autosomal dominant Autosomal recessive X-linked – are carried on X chromosomes Does anyone know how X-linked traits usually manifest in a family?  Punnet square T T t t  T t  T t https://www.khanacademy.org/science/biology/classical-genetics/mendelian--genetics/a/mendel-and-his-peas? Genetic inheritance – polygenic and complex Polygenic - trait by more than one gene (non-Mendelian) Poly = many These traits (e.g. skin colour, etc.) show continuous variation Complex - trait by more than one gene and environmental factors (e.g. height) https://www.khanacademy.org/science/ap-biology/heredity/ A study found that over 400 environmental-effects-on-phenotype/a/polygenic-inheritance- and-environmental-effects genes are linked to variation in height Genetic inheritance – polygenic and complex Many diseases are said to have ‘genetic risk factors’ e.g. type 2 diabetes and some cancers These diseases are thought to be made more likely by the presence of certain genes We will look at these diseases more in Genes 3 Mutations A mutation is a change in the DNA sequence of an organism Genetic mutations allow evolution to occur as well as many diseases A germ-line mutation is passed on through the gametes to the next generation Every cell in that new organism will carry the mutation A somatic mutation happens to a particular cell and cannot be passed on E.g. a mutation in a skin cell due to solar By Messrs. Maull and Fox - Scanned from Karl Pearson, The Life, Letters, and Labours of Francis radiation cannot pass on to offspring Galton., Public Domain, https://commons.wikimedia.org/w/index.php? curid=78245  Substitution mutations The effect of a genetic mutation varies in magnitude depending on how it disrupts the genetic code and resulting protein Can you think how effects vary, based on what you know about the triplet code? These types of mutation result from a replacement or substitution of a base https://commons.wikimedia.org/w/index.php?curid=12481467  Deletion or insertion mutations Deletion and insertion mutations are when amino acids are inserted or deleted from the protein sequence Can cause a frameshift (when bases are deleted or inserted NOT in multiples of 3) DNA sequence Amino acid sequence CAG Normal (wild-type) CCC ACT Gl Pr Th n o r Insertion CAG TCC CAC T Gl Se Hi ? mutation (frameshift) n r s Insertion CAG TTT CCC Gl Ph Pr Th mutation (non- frameshift) ACT n e o r Deletion or insertion mutations By Genomics Education Programme - Frameshift deletion, CC BY 2.0, https://commons.wikimedia.org/w/index.php?curid=50542989 Larger mutations Other types of mutations involve larger sections of DNA Large sections of a gene or even a chromosome can be amplified or deleted Sections of chromosomes can switch too, resulting in movement of gene(s) between chromosomes This can chop genes in half and inactivate them or it can change gene expression by putting them in different places From the National Human Genome Research Institute (NHGRI) Genetic Illustrations  Epigenetics We have looked at how genes are inherited and how they contribute to the phenotype of an organism Epigenetics is a growing field of research which explains stable, heritable traits that are NOT explained by the genetic sequence https://www.novusbio.com/research-areas/epigene “above the genes” Epigenetic information is conveyed through modification of DNA structure which can change the expression of genes An example of this is the addition of a methyl group to a DNA base (methylation) By Mariuswalter - Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php? Epigenetics https://en.wikipedia.org/wiki/Epigenetics Epigenetics Epigenetic changes can be caused by environmental factors The impact of the environment can therefore change what information an individual passes onto the next generation (on top of the genetic sequence information) Some research suggests that memory of trauma can be passed down E.g. mice that are exposed to a particular smell and a painful stimulus at the same time have offspring that are more likely to have an aversion to the same smell (see resources link) The biology behind this is not at all clear, but it is thought that epigenetic factors could be involved in human conditions including diabetes and addictive behaviours Summary Genome = entire set of DNA instructions found in a cell DNA is composed of nucleotides DNA is a code and a specific section of DNA makes a gene Transcription of DNA by the enzyme RNAof Translation polymerase RNA at the(U ribosome into proteins instead of T) into RNA Genetic inheritance – monogenic, polygenic, complex Mutations – germline and somatic Epigenetics - epigenetic changes are reversible and do not change your DNA sequence, but they can change how your body reads a DNA sequence Learning objectives By the end of this session, you should be able to: To revise and revisit core issues in genetics covered at a pre-university level; nucleotide bases>codons>genes>DNA>RNA To revise and revisit core Mendelian genetics, autosomal/x-linked, dominant/recessive patterns of inheritance covered at a pre-university level To introduce the theme of complex patterns of inheritance To define mutation and explain the terms inherited and somatic mutations To introduce the concept of genetic vs epigenetic effects and their significance We will look more at genes to proteins and at genetic diseases in Genes 2 and 3 Further reading Johnson, L. et al (2008). "Genetics and Its Implications for Clinical Dental Practice and Education: Report of Panel 3 of the Macy Study." Journal of Dental Education 72(2 suppl): 86-94. Genetics glossary https://www.genome.gov/genetics-glossary Overview of transcription https://www.khanacademy.org/science/biology/gene-expression-central-dogma/transcript ion-of-dna-into-rna/a/overview-of-transcription Chromatin https://www.nature.com/articles/nmeth.1673 Classical genetics https://www.khanacademy.org/science/biology/classical-genetics Punnett squares https://www.khanacademy.org/science/hs-biology/x4c673362230887ef:inheritance-and-v ariation/x4c673362230887ef:genes-traits-and-the-environment/v/mendelian-inheritance- and-punnett-squares Mutations https://www.khanacademy.org/science/ap-biology/gene-expression-and-regulation/mutati ons-ap/v/an-introduction-to-genetic-mutations Epigenetics https://www.cdc.gov/genomics/disease/epigenetics.htm#:~:text=Epigenetics%20is%20t he%20study%20of,body%20reads%20a%20DNA%20sequence