YR1 Lecture - Introduction to Genetics E O'Connor 2024 PDF

COPYRIGHT COMMONWEALTH OF AUSTRALIA Copyright Regula=ons 1969 WARNING This material has been reproduced and communicated to you by or on behalf of University of Western Sydney pursuant to Part VB of the Copyright Act 1968 (the Act). The material in this communicaDon may be subject to copyright under...

COPYRIGHT COMMONWEALTH OF AUSTRALIA Copyright Regula=ons 1969 WARNING This material has been reproduced and communicated to you by or on behalf of University of Western Sydney pursuant to Part VB of the Copyright Act 1968 (the Act). The material in this communicaDon may be subject to copyright under the Act. Any further reproducDon or communicaDon of this material by you may be the subject of copyright protecDon under the Act. Do not remove this noDce. 1 Introduction to Genetics Dr. Elizabeth O’Connor [email protected] Learning objectives Understand Mendel’s laws of genetic inheritance ~ how one ? you intempt - includes basic interpretation of Punnett Squares I Describe the structure of DNA how you create one ? Describe the processes and enzymes involved in DNA replication 3 Lecture overview What is DNA and a gene? Who is Mendel and what are his laws? Examples of human alleles The structure of DNA DNA replication processes Elderzakirov.com 4 References Gene$cs in Medicine, Thompson and Thompson, 10th Ed, 2024 Principles of Gene$cs, Snustad and Simmons, 7th Ed 2015 Molecular Biology of the Cell, Alberts et al., 7th Ed, 2022 5 What is DNA? Nuclear material containing the instruc1ons to build a living organism Made up of nucleo1de base pairs (A, T, G, C) on a sugar backbone Each human cell - ~3.5 billion bp Nucleus – organelle containing genetic mi material Chromosome – structure within which DNA is packaged (23 pairs in humans) Nucleosome – DNA wound around histone proteins Chromatin – unit of repeating nucleosomes Chromatid – 1 of 2 identical copies of a chromosome joined at the centromere (produced during replication) 6 What is a gene? Sequence of nucleo1de basepairs (bp) that code for a protein The hereditary unit, passed from parent to offspring (maternal We have two copies of every gene – one from each parent those small Large Genes can be from a 132 bps to >100,000 bps Human genome has >20,000 genes proteins go On to & porternal) produce protein. a - Genes ↑ have function around the body - 7 P O Q Some terminology Gene – piece of geneDc informaDon coding for a protein Allele – version of a gene Cressions) etc hair brown/blonde hair) Locus – fixed posiDon on a chromosome, usually occupied by a gene Homozygote – individual carrying 2 copies of the same allele Heterozygote – individual carrying 1 copy of each of 2 alleles of a gene (= hybrid) Maternal Paternal chromosome chromosome Locus Gene V Heterozygote for this gene Heterozygote for this gene same Heterozygote for this gene Red allele of this gene Blue allele of this gene 8 Some terminology Genotype = genetic complement of an individual Phenotype = physical expression of genotype in an individual Wild type (+) = typical phenotype or dominant allele in a population Autosome = chromosomes not involved in sex determination (humans = 22 pairs) Sex chromosome = chromosomes involved in sex determination (humans = 1 pair) Genotype Phenotype Wild type? Flower is red Yes, most of the flowers of this species are red bb (orange alleles “b”) Seed colour is orange No, most of the seed of this species are brown WW (green alleles “W”) Seed surface is wrinkly Yes, most of the seed of this species are wrinkly Ff (red allele “F”, blue allele ”f”) 9 Father of genetics Gregor Mendel 1822-1884 Observation that traits are passed through generations* Hypothesized that parents pass on “particulate matter” to offspring è Alleles (alternate versions of a gene) * 100 years before Watson and Crick describe DNA 10 Genetic inheritance patterns Mendel’s study of pea plants to determine patterns of inheritance Determined that some gene alleles are dominant and some recessive Three inheritance laws that dictate basic inheritance patterns o First law – segrega$on o Second law – independent assortment Pea-plant dominance o Third law – dominance 11 Mendel’s First Law The Law of Segregation Gene alleles have a random chance of passing from either mother to offspring or father to offspring The basis of a Punnett Square in predicting the chance of inheritance 12 Mendel’s Second Law The Law of Independent Assortment One set of alleles segregates independently from other sets during gamete formation (*if they are on different chromosomes) The genes for pea seed colour (yellow/green) segregate separately from the genes for seed shape (round/wrinkled) TH Morgan’s work in 1930s showed a minority of genes that are linked (eg. eye and body colour in fruit flies) 13 Mendel’s Third Law The Law of Dominance Recessive alleles will be phenotypically masked by dominant alleles The purple flower colour is dominant over white flower colour Flowers that carry one copy of the purple allele and one copy of the white allele will display a purple phenotype 14 Human alleles Straight thumb Hitchhiker’s thumb Straight hairline Widow’s peak Check your thumbs and your hairline – you may need the help of a neighbour or a mirror for the latter What do you have? 15 Human alleles Straight thumb Hitchhiker’s thumb - dominant - recessive Straight hairline - recessive Widow’s peak - dominant Other traits to look at – hair colour/curliness, eye colour, cleft chin, dimples, freckles, blood type * Many of these traits are controlled by multiple genes rather than a single gene with 2 alleles 16 Punnett Squares One parents alleles in the columns Other parents alleles in the rows Offspring in the boxes Phenotype ratios: 3 purple flowers: 1 white flower Genotype ratios: 1 RR: 2 Rr: 1rr -> Enables prediction of offspring ratios 17 Punnett Squares Phenotype ra$o A. 1 yellow: 3 green Yy crossed with yy B. 3 yellow: 1 green C. 1 yellow: 1 green y Genotype ra$o A. 1 Yy: 3 yy B. 1 Yy: 1 yy C. 3 Yy: 1 yy Y Y Y Y Yy by 39 YY. Parent I - y Y Yy Yy ·y yy yy of 18 Example David and Sally are both heterozygous for the recessive cys$c fibrosis mutant gene. What is the chance that their first child will be homozygous for the cys$c fibrosis mutant gene and suffer from the disease? Both C c Ca ↓ C C C CC Mutant Co - Ca Due to C (Recessive) CC LOOK OUT = gene = Cc d CC L neterozygous & homozygous gene both + parents having c - it each chance for the child ?? non typeindividual anner the because mutent gene is -Remember = I N = 1/4 won't wild present in me suffer from - this disease 19. Example David and Sally are both heterozygous for the recessive cystic fibrosis mutant gene. What is the chance that their first child will be homozygous for the cystic fibrosis mutant gene and suffer from the disease? Answer: 1/4 C c C CC Cc c Cc cc 20 DNA Deoxyribonucleic acid (DNA) is the genetic material that instructs our body cells how to function can The genetic material is grouped into units called genes inherited chemical These functional units are inheritable be structure ass nitrogen The base chemical structure is: -contained - nitrogen/carbon bases - on a sugar/PO4- backbone form · the sugar background phosphate & green nitroglod Nitrogenous base -missing gen base Pearson Education Ltd 21 Nucleic acid bases All life on earth is made from the same four bases - Adenine (A), Thymine (T), Cytosine (C), Guanine (G) - In RNA, thymine (T) is subs6tuted by uracil (U) 22 Pairing and reading DNA RNA A always pairs with T (or U in RNA) C always pairs with G hydrogen bondt A sequence of bases is “read” from the 5’ (5 prime) end to the 3’ (3 prime) end 23. Packaging Stretched out end to end, the length of DNA in a single cell measures 2m To fit, it needs to be packaged – a chromosome represents the packaged form of a section of DNA In humans, there are 23 pairs of chromosomes (one each from mum and one each from dad) National Human Genome Research Institute's Talking Glossary http://www.genome.gov/glossary/. 24 DNA Packaging (Metaphase) Nucleosome contains core histone proteins and linker H1 histone proteins Metaphase chromosomes are highly condensed for cellular replication 25 DNA Packaging video Molecular Visualizations of DNA; WEHImovies https://www.youtube.com/watch?v=OjPcT1uUZiE 26 Replicating DNA To produce a daughter cell, the DNA inside the nucleus needs to be replicated Mitosis -> identical daughter cell full replication nuckers See inste DNA all of [Meiosis -> gamete production, ½ genetic complement] offspring - DNA replication occurs during the S phase of a cell cycle McGraw-Hill 27 Replicating DNA DNA is synthesized at a rate of ~35bp/sec (every hour, every day) Errors occur at a rate of 2x10-10 errors/bp/replication (->100,000 errors per cell per cycle) Both strands of DNA must be replicated – slightly different processes For replication to occur, the DNA needs to be “unwound” or unpackaged 28 Enzymes in DNA replication -enzyme Topoisomerase – undoes the DNA super coiling Helicase – separates the DNA double strand making the bp sequence accessible Primase – synthesis of DNA primer (complementary sequence) main mryme-D DNA polymerase – adds bases to the new sequence, proofreads as it goes Ligase – Links the bases of the new sequence together 29 Steps in DNA replication Chain ini$a$on, chain elonga$on, chain termina$on 30 Chain initiation Initiator proteins bind AT-rich sequences complex Origin replication complex (ORC) forms and unwinds DNA (helicase) ORC highly complex set of proteins Allows formation of replication fork Co Multiple origins along DNA strands space that mociatio can happen 31 - Chain elongation - Leading strand An RNA primer (short seq bp) is initially added to template DNA polymerase begins to add DNA bps in 5’ to 3’ direction Elongation continues until replication meets an adjacent fork or the end of the chromosome - primer 32 - Chain elongation - Lagging strand DNA polymerase has to extend in 5’ to 3’ direction Several RNA primers are added at various regions Primers are extended in short sections called Okazaki fragments DNA ligase joins fragments together 33 Chain termination Once elonga*ng strand reaches another replica*on fork or the end of the chromosome, DNA polymerase is released RNase enzyme removes RNA primers, DNA pol fills in primer gaps with DNA Nicks (gaps) in sugar backbone are ligated (ligase) 34 Process of replication DNA replica=on – 3D; yourgenome haps://www.youtube.com/watch?v=TNKWgcFPHqw 35 Summary Mendel’s genetic experiments resulted in the Laws of Inheritance o Law of segregation > - get pain from mum/dod o Law of independent assortment o Law of dominance > - some > - gener alheres mas other or link to genes geathe are dominant areas of genes recessive , and which are can know as Punnett squares allow determination of predicted offspring genotypes for simple to do ↳ allow production about offspring genotype genetic crosses us DNA is made up of A, T, C, G nitrogenous bases on a sugar backbone DNA is highly packaged – coiling around histones (2m) DNA replication produces identical copies and is controlled by a series of specialised enzymes Replication consists of chain initiation, elongation (leading and lagging strands) and termination 36 Thank you! 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