ES9003 Quiz.pdf

By the end of this course, you should be able to: LO1. Describe how the Genomics and related technology are useful to assess risks in your health. LO2. Evaluate advantages and concerns on development of the life science technology and generating...

By the end of this course, you should be able to: LO1. Describe how the Genomics and related technology are useful to assess risks in your health. LO2. Evaluate advantages and concerns on development of the life science technology and generating genome information. LO3. Explain how life science technology change or impact human society. Intended LO4. Describe genetic differences between individuals and ethnicities and why Learning it’s importance to study them. Outcomes In addition, u Better understanding myself (humans and genetic background) and others (society) u Understand diversity and respect differences u Help your making decision in your life. 8  DNA (Deoxyribonucleic acid) DNA structure DNA chemical structure Double helix : video Rosalind Franklin Source: Differences between RNA and DNA Source: Structure of Nucleic Acids Source: Griffiths, A., Wessler, S., Carroll, S., & Doebley, J. (2015). Introduction to genetic analysis (Eleventh edition.). New York, NY: W.H. Freeman & Company. 10  DNA characteristics § Inheritable: complementary base pairing structure is accurately replicable, stable, DNA and inheritable to next generation. : inheritable § Informative: four types of genetic nucleotides can save/code genetic information. materials § Variable: the changes in DNA sequence can result in difference between individuals and drive for evolution. Source: Griffiths, A., Wessler, S., Carroll, S., & Doebley, J. (2015). Introduction to genetic analysis (Eleventh 11 edition.). New York, NY: W.H. Freeman & Company.  RNA vs DNA Ribose sugar Deoxyribose sugar Single-stranded Double-stranded Unstable molecule Stable molecule Codes Amino Acid Storing and and play several roles transferring Uracil instead genetic Thymine information 12 Source: The Structure of DNA Source: Differences between RNA and DNA  Human chromosomes Chromosomes Thread-like structures made of proteins and a single molecule of DNA Source: http://www.nicerweb.com/bio3400/Locked/media/ch01/ 01_03-human_karyotype.jpg § Each cell contains a fixed number of chromosomes. § The chromosomes in the cells are present in pairs, one from mother and one from farther. Source: Griffiths, A., Wessler, S., Carroll, S., & Doebley, J. (2015). Introduction to genetic analysis (Eleventh edition.). § Human genome have two sets, diploid, of New York, NY: W.H. Freeman & Company. chromosomes, 2n=46. 13  Central dogma Chr 10 Gene The physical unit of nucleotide sequences that encode a single Source: https://www.cancer.gov/about-nci/organization/ccg/blog/2020/intro- molecule (ex. Protein, RNA). proteogenomics-central-dogma § Gene produce proteins : Proteins function in cells : Maintain life of living organisms. § Gene is a basic unit of inheritance : Gene sequence is conserved across different species. Source: Merlin G. Butler, Syed K. Rafi and Ann M. Manzardo. "High-Resolution Chromosome Ideogram Representation of Currently Recognized Genes for Source: https://www.genome.gov/genetics-glossary/Gene Autism Spectrum Disorders." Int. J. Mol. Sci. 2015, 16(3), 6464-6495; doi:10.3390/ijms16036464 14  *base pair (bp): unit of Genome nucleotide acids, A, G, C, T 1 Kb = 103 bp The complete set of genetic 1Mb = 106 bp information 1Gb = 109 bp § Genome provides all the information which the organism requires to function. § Genome size are various by organisms. Human genome size is ( ) Gb, including ~20,000 protein coding genes Source: https://cs.stanford.edu/people/eroberts/cs201/projects/2010- SARS-CoV-2 genome size is ( ) Kb, including 11 genes 11/Genomics/accuracy.html 15 Q. Genetic difference between human and chimpanzee? 16 The First Sanger sequencing (Frederick Sanger, 1977) Sequencing technology Source: https://frameworker.wordpress.com/2008/08/01/gel-tracker/ Source: https://www.flickr.com/photos/jurvetson/57080968/ 17 The First Human Genome The goal of the project is building the human reference genome. The project cost $3.8 billion USD over 13 years (1990-2003), coordinated by the US Department of Energy and the National Institutes of Health. The economic impacts generated by the project was $965 billion ($293 personal income and 4.3 million job-years of employment ). The Human Genome Project 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 Source: The draft human genome. Nature 489, 54 (2012). https://doi.org/10.1038/489054a 18  Individual Genome Ø The first complete personal genome (single individual) Ø Sequenced by next-generation sequencing technologies (1M USD for 2 months) James Watson Genome Craig Venter Genome 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 Source 1: https://commons.wikimedia.org/wiki/File:James_D_Watson.jpg#/media/File:James_D_Watson.jpg Source 2: J. Craig Venter, PhD | The MedTech Conference. Retrieved 19 February 2020, from https://themedtechconference.com/craig-venter-2/ 19 Genome Next Generation sequencing (since 2005) sequencing Commonly used high throughput methods Illumina Pacific Oxford Biosciences Nanopore Source: https://www.labiotech.eu/in-depth/portable-sequencing- Source: https://www.youtube.com/watch?v=NHCJ8PtYCFc genetics-research/ Source: https://www.youtube.com/watch?v=fCd6B5HRaZ8 Space station 20 NovaSeq X plus ~64 human genomes/run Instrument Cost: 1.25M USD $200/genome $7000/genome Ultima Genomics (~33 human genomes/run) Instrument Cost: 1.5M USD $100/genome Sequencing cost  Government projects § To develop precision § UK: Genome England Personal medicine § USA: All of Us Research program Genomics § Diagnosis of disease for § China: China Kadoorie Biobank patients § Iceland: DeCode Genetics § Japan: Tohoku Medical MegaBank § Genetic testing for § Qatar: Qatar Genome preventing § Singapore: PRECISE § Saudi Arabia: Saudi Human Genome Program Industry-driven project § Human longevity Inc. § Verily Life Sciences § Regeneron Genetics Center § GenomeAsia 100K Source: Wiley Analytical Science. (2020). Retrieved 19 February 2020, from https://genomeasia100k.org/ Genomics extend science fields Genomics as driving force to improve: § Data science (Bioinformatics) § Evolutionary genetics § Development biology The decrease in sequencing cost extend the field. § Medicine/public health § Phenomics § Microbiology (Metagenomics) § Environmental science § Forensics § Agriculture/food 23 Topics: Define: – Who are you (researcher, What government, NGO, industry, …) – Aim genome data – Samples would you – Number of the samples generate? – Benefits of the data generation 26  Genome sequencing projects Eukaryotes: Biodiversity Projects Source: https://gold.jgi.doe.gov/statistics  Government projects § UK: Genome England § USA: All of Us Research program Personal § China: China Kadoorie Biobank § Iceland: DeCode Genetics Genomics § Japan: Tohoku Medical MegaBank § Qatar: Qatar Genome § Singapore: PRECISE § To develop precision § Saudi Arabia: Saudi Human Genome Program medicine § Diagnosis of disease for Industry-driven project patients § Human longevity Inc. § Genetic testing for § Verily Life Sciences preventing § Regeneron Genetics Center § GenomeAsia 100K 4 Genetic difference between individuals §Genetic variants generate genetic difference between individuals. §3~4 Million SNPs between a pair of individual in average. No. of Total no of §Growing population Babies de novo Mutations generates more variants born in 2020 mutations per birth per year in the population. (Kong et al. 2012) Source:www.obitsushop.com 6  Genetic difference between populations § Non-random mating results in difference between populations. § Non-random mating by isolation (geographically, religion, endogamy), migration (geographic distance), preference (morphology, culture, Population language) > Population split split (structure) > ethnicity § Genetic differences are in allele frequencies of variants between populations (common variants), and population-specific variants Alleles (rare variants)  Human migration history : human populations are structured. *The map is based on mitochondrial DNA. 8 Source:www.mitomap.org  Human population structure Estimated ancestries using genome data § Each bar indicates an individual. § The Y axis is the proportion of each ancestry in each individual genome. 9  Population Admixture Estimated ancestries using genome data African American § Each bar indicates an individual. § The Y axis is the proportion of each ancestry in each individual genome. § Admixture (gene exchange between distinct populations) generates mosaic ancestry structure. 10 Ancestries in an individual genome Desmond Tutu Recombination Analysis from Kim et al, 2014 11  Large genetic diversity in Asians Gujjar Paniya Birhor Jarwa Kensiu Aeta Baining Indo-European Southern Indian Austroasiatic Andaman Orang Asli Philippine Negrito Papuans Mentawai Flores Dai Buryat Quechua Nature 576, 106-111 (2019) pdf Austronesian Eastern Indonesian Thailand/China Mongols South American 12  Lack of the Asian ancestries in public data GenomeAsia 100K (~1700) 1000From 1000 genome genome (~2500) projectproject (2015) 13 African European South Asian East Asian American Missing diversity in Human genetic studies Ancestry Proportion Ancestry Proportion in in Genome database GWAS(Genome wide association study) Sirugo et al, 2019 All of Us project in the US TOPMED 14 Ancestry matters on the function of variants Risk of Primary open angle Genetic studies (Liu et al, 2013) glaucoma CDKN2B-AS1 gene (>40 years old) African SNPs Caucasian African 6 American rs4977756 strong significant no strong no no Risk (%) rs10116277 4 rs4977574 strong no no 2 rs10120688 no strong no rs16905597 no significant no 0 rs10965245 no significant no Caucasian African African American 15 https://www.biorxiv.org/content/10.1101/2024.05.20.594987v2.full  Genetic differences impact on your life Predicted Adverse Drug Responses Risk Ø Demographic history differentiated genetic background between populations. Ø The genetic difference results in different level of risks. Nature 576, 106-111 (2019) pdf 16  Microbes are everywhere もやしもん Metagenomics unravel Microbiomes. Terrestrial Aquatic Air Total Number of 2.6 × 1029 cells 1.2 × 1029 cells 5 × 1019 cfu (?) cells Luhung, I., Uchida, A., Lim, S.B.Y. et al. npj Biofilms Microbiomes 7, 37 (2021). https://doi.org/10.1038/s41522-021-00209-4 Microbiome COMPOSITION OF A MICROBIAL COMMUNITY  20 Metagenomics Metagenome video Zhang et al, 2017 20 Environmental DNA Species Identification (community composition) Environment surveillance (drinking water, food) Biodiversity monitoring and assessment Construct ecosystem (food chain) Conservation (illegal trading) Forensic Thomsen and Willerslev, 2015 21 Human Microbiome Hou et al, 2022 Nurkolis et al, 2022 Topics: § What is the concept of One Health? One Health § What would be a role of One Health to improve the public health care? § What could be a role of Genomics in One Health? Reading material: One health report 25 Genetic variations § DNA replication error causes a Mutation mutation and changes a DNA sequence. Parent AAGCTGCTGGCT Child1 ATGCTGCTGGCT § Point mutation results in Single Child2 AAGCTGCTGG-T Nucleotide Polymorphism (SNP) or Insertion/Deletion (Indel). SNP Indel A>T C>- 5  Genetic codon § Codon is a group of 3 nucleotide sequences that code a specific amino acid. § Amino acid is a unit of proteins. § Genetic variants can change amino acids. * ‘T’ of DNA transcripts to ‘U’ of RNA. Source: https://upload.wikimedia.org/wikipedia/commons/f/f2/0324_DNA_Translation_and_Codons.jpg 6  Consequences of SNPs Codon table TAC Synonymous (Tyr) TAT CAT Nonsynonymous (Tyr) (His) TAA Nonsense mutation (Stop) Variants do not always affect on functions of proteins. Source:Griffiths, A., Wessler, S., Carroll, S., & Doebley, J. (2015). Introduction to genetic analysis (Eleventh edition.). New York, NY: W.H. Freeman & Company. 7  Genotypes and Phenotypes Allele B (A) b (G) Genotype § Genotype is the individual genetic information. § Phenotype is the expressed trait of the BB (AA) Bb (AG) bB (GA) bb (GG) genotype. Homozygote Heterozygote Heterozygote Homozygote § Traits can be Phenotype Dominant expressed in various types. Recessive Incomplete dominant Genetic Dominance Source: https://en.wikipedia.org/wiki/Zygosity#/media/File:Heterozygous.jpg 8 SNPs and traits of humans NCBI: rs4680 SNPedia: rs4680 Examples: rs713598 rs1426654 rs17822931 rs12913832 9  Mendelian Inheritance Symbols in pedigree Inheritance of Recessive disorder § The disease related gene is located on the X chromosome. § Female Heterozygote(XAXa) is not affected but can carry the disease allele(Xa). § Female homozygote(XaXa) or Source: Symbols used in human pedigree analysis.(After W. F. Bodmer and L. L. Cavalli- male heterozygote(XaY) are Sforza,Genetics, Evolution, and Man. Copyright © 1976 by W. H. Freeman and Company.) affected. Source:Griffiths, A., Wessler, S., Carroll, S., & Doebley, J. (2015). Introduction to genetic analysis (Eleventh edition.). New York, NY: W.H. Freeman & Company. 10  u A trisomy has three copies of one of chromosomes (2n+1). u The egg or sperm may have an extra chromosome due to fail of Chromosome chromosome separation (non-disjunction) in the process of egg or sperm cell generation. abnormalities § Highly related to age u A trisomy often results in miscarriage, but sometimes survive to birth. § Trisomy 21 (Down syndrome) § Trisomy 13 (Edwards syndrome) XXX (Triple X syndrome) 1 § § XXY (Klinefelter syndrome) § XO (Turner syndrome) 11 1 Topics: Genome information will impact on your marriage? u Will you ask the genetic test results from your partner? Assuming you plan to have a child, you can think about: What are important factors you consider for selecting your partners? What information you can/want to obtain from genetic test? What information you want to have if you don’t ask genetic test? What will be the risk you can estimate based on the test results? What is your recommendation for the couple who are planning a marriage? How this technology impact on human marriage? Case Study examples: Genetic compatibility test Dor Yeshorim Genetic matchmaking 15