How To Sequence The Human Genome-Mark Kiel

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HOW TO SEQUENCE THE HUMAN GENOME-MARK KIEL

 Human genome - huge collection of genes in each cell; sequence to human genome
 Genome - is all the genes plus extra that make up an organism; Code of cells to know how
to behave
 Genes - made up of DNA
 DNA- made up of long pairs of strands ATCG
 First human genome – Year 2003
 Knowing the sequence - goal of genome sequencing
 to get that information, one must break chain of DNA and each break is sequenced
individually
 signal to detect the letters - use enzymes to make thousands of copies of each genome piece
 colorful spots are stitched together through computer programs to create a complete
sequence of an entire genome; most common way
 interpreting genes of genome is worked on to identify differences in traits

CRISPR

 Clustered Regularly-Interspaced Short Palindromic Repeats


 Repeats short segments of DNA (20-40 letters in length); they are in palindromes or
sequence of letters that read the same from left to right
 spacer DNA are not identical and unique; important DNA; matches perfectly with viral
DNA
 CAS genes (CRISPR associated genes)
 CAS genes will make CAS proteins
 CAS proteins are going to be helicases that unwind DNA and nucleases, cutting the DNA
 CRISPR is spacer repeat pattern where spacers are history of old infections, so infection
won't happen again; how immune system works in a larger level
 activate and embed new genes
 CRISPR CAS 9 system - Jennifer Doudna and Emmanuelle Charpentier
 streptococcus pyogene and Cas-CRISPR system; Has only one system – CAS 9
 making new RNA - CRISPR CAS 9 system; 1 CAS 9 protein and chimera or gRNA
 engineer a new embryo
 CRISPR system is an immune system that was identified in bacteria and modified in
humans

GENOMICS

 Genomes - set of instructions to create an organism and stored in cells as DNA


 DNA (deoxyribonucleic acid) - molecule that stores information by using a special code
 Genome is like a coded cookbook
 Human genome - 23000 recipes that code for different proteins
 Gene - functional unit of DNA; 2% codes for protein and rest is non-coding DNA
 Genetics - study of DNA
 Genomics - study of genome and environment
 Power of genomics - Human Genome Project: goal is to read the entire human genome
 How genomics is improving lives: two made-in-Canada examples:

Example 1: Copy Number Variation (CNV)

- human genome contains 2 copies of any segment of DNA


- large segments of DNA can be duplicated or deleted in the genome
- Copy Number Variations (CNV) contribute to uniqueness and susceptibility to disorders

Example 2: Combating the Mountain Pine Beetle

- Western Canada: mountain pine beetles destroy trees through a fungus


- genome level: forestry management strategies

 Speed of genomics: human genome project is done in 13 years and is worth 3B dollars
 Expanding knowledge on genomes: compare genomes, alikeness, evolutionary history
 Open access: positive applications in life, agriculture, environment, medicine
 Genomics is
1) Holistic in scope - studies all genetic information in an organism and how it interacts
with its environment
2) High throughput - reads and analyzes large amounts of DNA info quickly and
efficiently
3) Resource generating - enables research and discovery

GENETIC ENGINEERING

 genetic engineering--genetic code of an organism is altered to produce a desired trait; done


by taking a gene of one and inserting it into the DNA of another to get a wanted result
 DNA - acts as the instruction manual for the body
 certain genes code for certain proteins: color, shape, etc. (traits)
 all living things use the same genetic code, DNA, and scientists use special enzymes to
cut parts from one living thing and sew to another
 result is a living thing with new gene and new feature
 examples where genetic engineering is used-- food, research, medicine
 Medicine-Humulin - medication used for diabetics; created with genetically modified
bacteria and given to diabetics who lack insulin; section of DNA that codes for insulin -
enzymes that can cut the DNA and isolate gene and insert it in DNA of bacteria
 End result is a bacteria that produces human insulin in a short amount of time

SYNTHETIC BIOLOGY

 Genetic manipulation by selective breeding


 Engineers treating DNA more like a programming language
 use DNA to write simple Lego-like functional components inspired by but not found in
nature and run them in a cell instead of a computer
 re-engineered genetic engineering is known as synthetic biology
 instead of copy pasting a sequence, just type the DNA sequence or copy or select from a
catalog and database and just order it on the internet
 DNA is copied from nature but DNA itself is made by machine
 Biobricks is open source catalog of over 5000 standardized components
 Biobricks - projects that are inserted in a studied intestinal bacteria- E.coli (gut bacteria)
 E. chromi - E. coli with sensitivity tuner and color generator is programmed to turn one of
5 colors when it detects a certain concentration of an environmental toxin
 E. Coliroid - bacterial system which switches on and off in response to red light and acts
like a bacterial polaroid camera
 Jay Keisling - built a new metabolic pathway in yeast by assembling 10 genes from 3
organisms
 Artemisinin-treat malaria
 Craig Venter - replaced entire DNA of bacterium with a synthetic copy of DNA from
another naturally occurring species and added a few extras
 reprogram ability of bacteria cell
 Biological factories to make many things such as medicine vaccine, food and fuel
 engineering algae - eat carbon dioxide and produce less polluting biofuels
 liver and kidney transplants - use a vat grown, all-purpose and biological sieve organ
called “kliver”
 change nature of construction, architecture, urban planning, forestry, gardening

PROTEOMICS: PROTEINS AT WORK

 Michael Snyder - Professor and Chair of Genetics in Stanford University, Director for
Center for Genomics and Personal Medicine, NASA Twins Study Investigator
 targets of drugs are proteins that do work in the body
 proteins come from DNA but not directly made from DNA
 proteins are made through RNA and instructs yourself to make proteins
 collection of proteins is called proteome
 mass spectrometry- tool for seeing thousands of proteins at once in blood
 blood is garbage can of body; when cells die, it will wind up shedding diagnostic proteins
into blood
 study blood to see unusual proteins
 discover new proteins that are made into biomarkers
 Biomarkers reflect diseases or indicate that something’s wrong
 Prostrate cancer - Protein PSA
 analyzing proteins can help in: therapies, DNA information, drug response based on DNA
sequence

CENTRAL DOGMA: DNA TO PROTEINS

 DNA - all living organisms share a genetic code


 Francis Crick (1956) - DNA is an informational storage molecule capable of replicating
itself
 Central dogma of molecular biology - information is read by a manufacturing body
within the cell which puts amino acids in a specific sequence in synthesizing a protein
 DNA serves as template for synthesis of a messenger RNA molecule is Transcription
 Translation - MRNA is read at a ribosome by transfer rna which assemble the amino acids
to create a protein
 Protein - cell's internal machinery
 specific 3D shape that determines function
 DNA - genetic storage; stored file in hard drive; mRNA - message sent to the printer;
ribosome - printer; protein - essay; letters - amino acids
 DNA indirectly codes for proteins; production of RNA molecules
 DNA and RNA are biological molecules known as nucleic acids
 nucleic acids- made of polymers that are made of repeating molecules which are
monomers (nucleotides)
 nucleotides - composed of three components: sugar, phosphate group, and nitrogenous
base
 DNA - double stranded nucleic acid composed of monomers known as
deoxyribonucleotides; made up of 3 components: phosphate group, sugar deoxyribose, and
1/4 nitrogenous bases
 Nitrogenous bases: Adenine, Guanine, Thymine, Cytosine
 based on shape- thymine and cytosine are pyrimidines; purines are adenine and guanine
 ribonucleotides are identical to deoxyribonucleotides
 phosphodiester bond - bonds made by nucleotides
 phosphodiester linkage- phosphates and sugar
 phosphate is the 5' end. The sugar is the 3' end. primary structure is 5' to 3'
 RNA molecules are responsible for actively synthesizing proteins

STEM CELLS

 Stem cell - Basic cell that give rise to all the different cells in different organs
 One type of stem cell is the egg cell of a woman that is fertilized by sperm from a man
 Zygote -first cell in the developing human being; also called totipotent stem cell; it can
form any type of cell in the body as well as placenta and umbilical cord
 Blastocyst - early stage embryo
 embryonic stem cells come from the cells inside blastocyst
 Embryonic stem cell - pluripotent cell; can form any cell in the body but not in umbilical
cord and placenta
 embryonic stem cells in labs are donated from leftover embryos created in "In vitro
fertilization"
 In vitro fertilization - procedure to help a woman become pregnant
 Adult stem cell - other type of stem cell; found in organs such as skin; multipotent cell;
only become a few cell types related to organs where they are found
 Regular body cell - cause it to change into induced pluripotent stem cell in the lab
 embryonic stem cells become induced pluripotent stem cell and can become any type of
cell in the body
 stem cells will be used regrow tissues and organs that have been damaged by injury or
disease
 stem cell therapy - procedure that uses stem cells to treat a disease/condition; cancers of
the blood;
 Leukemia - bone marrow makes abnormal white blood cells that can't do their job of
fighting infection
 hematopoietic stem cell transplantation - sample of blood or bone marrow is taken and
donor blood may come from umbilical cord of newborn; hematopoietic (blood-forming)
stem cells
 chemotherapy drugs - radiation to kill abnormal WBC and stem cells
 transplant hematopoietic stem cells to form new blood cells and fight off infection

BREAKING DOWN THE LAUDATO SI

 Laudato Si- encyclical that is dramatic and joyful; means "Praise be to you"; calls on
Christians to care for creation
 Problems faced: pollution, global warming, drinkable water, disappearance of animals
 Problems are caused by mankind
 problem is not environmental but an ethical issue
 lack of interest - denial of problem to indifference
 called to ecological conversion; we are protectors of God's handiwork
 saving the earth not an option or secondary
 What must be done:
 consistency on environmental activists’ part
 admire nature - inner reflection
 responsible with the mission God entrusted to mankind with Creation--cultivate and
care for the garden He has placed us
 effect of imbalance can be reduced by decisive action here and now
 we are part of the solution
 recycle, separate garbage, put a sweater instead of turning on heater

LAUDATO SI PLEDGE

 live it  join the advocacy of protecting our


 pray for and live creation common home
 live more simply  for the next generation

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