Cell – the basic structural and functional unit of all living th ings. Genome – the set of hereditary information encoded in the DNA of an organism, including both protein-coding & non-protein coding sequences. Gene – A DNA sequence coding for a single polypeptide. The fundamental physical unit of heredity w/c occupies a specific chromosomal locus.

3 primary branches of the tree of life Prokaryotes- e coli Eukaryotes- Archaebacteria- extremely high conditions

Mus musculus= mice

Human and mice have similar genes and development Kit gene- same mutation with mice, pigment cells

Arabidopsis thaliana- grown indoors, large numbers Drosophila melanogaster- proof of existence of gene Polytene chromosome- giant chromosome, due to many rounds of replication w/o cell division Caenorhabditis elegans- hermaphroditic, short life span Saccharomyyces cerivisiae- fungi, reproduce vegetatively or sexually, small genome Danio rerio- transparent for first 2 weeks of its life Xenpus laevisn- frog, vertebrate development

Mutations Intragenic mutation- gene is modified because of error during replication Gene duplication- give rise to families of related genes Once a gene has been duplicated, one of the 2 gene copies is free to mutate & become specialized to perform a different function w/in the same cell. DNA segment shuffling- 2 existing genes rejoin to become hybrid Horizontal transfer- DNA is transferred to genome of another cell, sometimes species

Orthologs- 2 separate species from same ancestral gene Paralogs- related genes result of gene duplication, diff functions

Viruses- bacteriophages Vectors for gene transfer Horizontal gene transfer- responsible for penicillin-resistant gonorrhea Sexual reproduction is example of horizontal gene transfer

Classification of functions Information processing Cellular processes and signaling Metabolism Poorly characterized

Mutation- alteration in DNA, source of new alleles

Conserved regions- unchanged subregions within the gene, most important

Human Genome Project- international scientific research project, goal is to determine sequence of human dna, mapping all genes of human genome

Translational medicine- a process in genetic findings are directly translated into new methods Statin drugs- lowering LDL cholesterol (PCSK9 gene- controls LDL levels) Familial hypercholesterolemia- high LDL cholesterol levels PCSK9 protein binds to LDL receptors on liver cells, receptors return to cell surface and remove LDL

Cultivation of plants- 5000 bc Animals were domesticated and selective breeding

Humors- body part that served as bearers of hereditary traits Aristotle- vital heat from semen provided capacity to produce offspring Vital heat cooked menstrual blood produced by females

THEORIES Theory of epigenesis (William Harvey)- organism develops from fertilized embryo to adult by developmental events Preformation theory- complete miniature adult, a homunculus Theory of Natural Selection (Charles Darwin)- populations more offspring than environment= struggle for survival= heritable traits to adapt The Chrosome Theory of Inheritance (Walter sutton and Theodore Boveri)- inherited traits are controlled by genes that reside in the chromosome transmitted through gametes for genetic continuity

Matthias Schleiden and Theodor Schwann- cell theory, all organisms are composed of cell from pre-existing cells Louis Pasteur- disproved spontaneous generation Charles Darwin- “origin of species”. Existing species arose by descent w/ modification from ancestral species

How a new species form- population is isolated, variations of inherited traits accumulate

Gregor Johann Mendel- general model of how traits are inherited Carl Correns, Hugo de Vries, and Erich Tschermak- enlightened mendel’s work

Alleles- alternative forms of a gene Mutant genes- used as markers, location of genes on chromosome

Why proteins as carriers of genetic information- proteins’ universal distribution Avery, Macleod, and McCarty- DNA is carrier of genetic information James Watsona nd Francis Crick- structure of DNA

Difference of DNA and RNA- contains different sugar in its nucleotides and uracil instead of thymine for nitrogenous base. RNA is single-stranded.

Enzymes- largest category of proteins, biological catalysts, lowering energy of activation Proteins Hemoglobin- oxugen in RBCs Insulin- pancreatic hormone Collagen- connective tissue Actin and yosin- contractile muscle proteins

SICKLE CELL ANEMIA Mutation in gene encoding B-globin causes amine acid substitution in 1 of 146 amino acids in the protein Diagnosed patients have 2 mutant cells of beta-globin gene= sickle cell anemia Mutant b-globin causes hemoglobin molecules to polymerize when oxygen is low Easily break, block blood flow, pain and damage

Chapter 1 Intro to Genetics (book) CRISPR-Cas Ability to rewrite DNA sequence Why? More efficient More accurate More versatile Easier to use “Seek and destroy” bacteria CRISPR (clustered regularly interspersed short palindromic repeats) refers to the part of the bacterial genome that produces RNA molecules. CRISPR RNA binds to a matching sequence in the viral DNA Cas nuclease- scissors and cuts DNA Epigenesis Preformationism- fertilized egg contains a complete miniature adult (homunculus) Matthias Schleiden and Theodor Schwann- proposed the Cell Theory Louis Pasteur- disproved spontaneous generation

The Cell Theory- all organisms are composed of basic structural cells which are derived from preexisting cells

Charles Darwin 1859- “On the Origin” of Species published by Charles Darwin Natural selection- Alfred Russel Wallace evolutionary change Population growth is aided by environment adaptation of heritable traits for survival If reproductively isolated, they become a new species

• The gap in Darwin Theory- lack of understanding of genetic basis of variation and inheritance

• Chromosome Theory of Inheritance- heredity and development were dependent on genetic information in genes contained in chromosomes which were then contributed to each individual by gametes

Gregor Mendel An augustinian monk Genes- “a pair of factors” Members of a gene separate from each other during gamete formation for genetics

The Chromosomal Theory of Inheritance Diploid number (2n) Humans: 46 diploid number Mitosis Chromosomes are copied and distributed so each daughter cell receives a diploid set of chromosomes identical to those in the parent cell Meiosis Gamete formation Cells produced receive only one chromosome from each chromosome pair haploid Sutton and Boveri- formulated the theory The Chromosomal Theory of Inheritance- inherited traits are controlled by genes residing on chromosomes transmitted through gametes, maintaining genetic continuity from generation to generation.

Genetic Variation Mutation- heritable changes in the DNA sequence Allele- alternative forms of a gene Phenotype- observable features Genotype- set of alleles for a given traits

DNA is the carrier of genetic information- Oswald Avery, Colin Macleod, and Maclyn McCarty (discovered through white-eyed Drosophila)

The Structure of DNA and RNA James Watson and Francis Crick- structure of DNA is a double helix Nucleotides- subunits (Adenine, Guanine, Thymine, Cytosine) RNA- single stranded (ribose than deoxyribose)

Gene Expression Transcription the nucleotide sequence in one strand of DNA is used to construct a complementary RNA sequence mRNA- binds to a ribosome Translation Synthesis of proteins Codon- triplet of proteins, complementary to DNA Proteins- polymers made up of amino acids (20 kinds) rTNA- recognize the information encoded in the mRNA codons and carry the proper amino acids for construction of the protein during translation.

Enzymes- form the largest category of proteins. The central dogma of molecular biology -- that DNA is a template for making RNA, which in turn directs the synthesis of proteins -- explains how genes control phenotype.

Sickle Cell Anemia caused by a mutant form of hemoglobin 2 mutant copies of the b-globin gene Deformed cells are fragile and break easily (lesser red blood cells) Sickles-shaped cells block blood flow in capillaries and small blood vessels Hemoglobin- protein that transports oxygen

DNA Cloning- Dolly Restriction enzymes- used to by bacteria to cut and inactivate DNA Vectors- DNA fragments Genome- complete haploid DNA content of a specific organism Dolly- a finn dorset sheep from the genetic material of an adult mammary cell

Transgenic Organisms- transfer of heritable traits across species

Genomic, Proteomics, and Bioinformatics Genomics- study of genomes Proteomics- identifies set of protein present in a cell under conditions Bioinformatics- created to develop hardware and software for processing nucleotide and protein data

Reverse genetics- sequence is known but function not so Gene Knockout- render targeted genes nonfunctional

Model Organisms organisms used for study of basic biological processes Caenorhabditis elegans- few hundred cells Arabidopsis thaliana- short life cycle Danio rerio- study vertebrate development, produces rapidly and transparent

Chapter 2.1 Mitosis (ppt) Chromosomes- vehicles for transmitting genetic information

Mitosis- somatic cells Meiosis- production of sex cells (gametes)

1940- year when transmission electron microscope was developed Electron microscope- allowed cells to be seen in highly organized structures (form and function) Mitochondria and chloroplasts- contain their own unique genetic information

Plasma membrane- outer covering that defines cell boundaries and delimits cell from external environment Cellulose- polysaccharide, what the cell wall is made of Glycocalyx- cell coat, provides biochemical identity, cell-identity markers Receptor molecules- recognition sites, transfer chemical signals across the cell membrane into the cell

Animal Cells- plasma membrane, glycocalyx Plants cells- cell wall

Chromosomes- what chromatin fibers condense into rRNA- ribosomal assembly NOR (nucleolus organizer region)- portions of DNA that encode rRNA ER (endoplasmic reticulum)- compartmentalizes the cytoplasm, increasing the surface area for biochemical synthesis Ribosome- serve as site where genetic information contained in mRNA is translated into proteins Mitochondria- oxidative phases of cell respiration, generate ATP Chloroplasts- photosynthesis Centrioles- located in centrosome, organizes spindle fibers Tubulin- protein polymers, what microtubules are made of Centrosomes- responsible for organizing microtubules into the spindle fibers Cohesin- multi-subunit protein complex holding sister chromatids together, formed during s phase Metaphase plate/ equatorial plane- midline region of the cell Kinetochore- plates of proteins where spindle fibers bind Shugoshin- protein family “guardian spirit” protects cohesin from being degraded Separase- enzymes that degrades cohesin Middle Lamella- cell plate laid down during telophase

Why “p” arm and “q” arm? P for petite and Q because it is the next letter

Karyotyping- chromosomes are photographed, cut out, printed, and matched up Locus/Loci- identical gene sites

Zygotes- single-celled fertilized egg Mitotic activity- basis for wound healing and cell replacement Reticulocytes- shed their nuclei and replenish the supply of red blood cells in vertebrates

Karyokinesis- nuclear division Cytokinesis- cytoplasmic division

Interphase- the initial stage of the cell cycle, replication of DNA

Cell Cycle Sequence= G1, S, G2, M G1, G2, S phase= intensive metabolic activity, cell growth, and cell differentiation By the end of G2, the volume of the cell has doubled

Vitro- “in glass”

Time Interval of Cell Cycle G1- 5 hrs S- 7 hrs G2- 3 hrs M- 1 hr Prophase- 36 mins Metaphase- 3 mins Anaphase- 3 mins Tel- 18 minutes

Prophase- cell phase migrating 2 pairs of centrioles Prometaphase & Metaphase- migration of every chromosome Prometaphase- chromosome movement Metaphase- chromosome configuration Anaphase- chromosome distribution, shortest stage of mitosis Telophase- 2 complete sets of chromosomes are present, one set at each pole

For complete disjunction to occur: Shugoshin must be degraded The cohesin is cleaved by separase Sister chromatids are pulled towards opposite poles

Difference between plant and animal cell cytokinesis? Plants just have a metaphase plate down the middle, animal cells undergoes constriction

CDC mutations- mutation that exert an effect at one or another stage of the cell cycle Kinases- enzyme products of many of the mutated genes, can add phosphates to other proteins Cyclins- molecules that control conjunction with proteins, bind to kinases Cyclin-dependent kinases- phosphorylate target proteins that regulate the progress of the cycle

Chapter 2.1 Meiosis (ppt)

Why must meiosis be very specific? Haploid gametes must contain precisely one member of each homologous pair of chromosome for genetic continuity

Crossing over- meiotic event resulting in genetic exchange between members of each homologous pair thus genetic variation

Prophase 1 Synapsis- pairing up of homologous chromosomes Bivalent- synapsed pair of homologs Tetrad- 2 pairs of sister chromatids Dyad- half of a tetrad Chiasma- chromatids are intertwined, crossing over Terminalization- chiasmata shift towards the chromosome ends

Leptotene- homology search Zygotene- synapsis, pairing up Pachytene- recombination Diplotene- chiasmata formation Diakinesis- separation

Metaphase 1- chromosomes are shortened and thickened

Spermatogenesis- productions of male gamete, Oogenesis- production of a female gamete Spermatogonium- diploid germ cell Spermatocyte- male gametocyte, sperm Ova- female gametocyte, egg cell

Equal amount of genetic material but unequal amount of cytoplasm because it is needed to nourish the developing embryo

Diploid sporo[hyte stage and haploid gametophyte stage- life cycle of multicellular plants

Why is Meiosis important? Serves as a bridge between the sporophyte stage (mitosis) and gametophyte stage (reproduction) of the life cycle Mechanism that reduces diploid amount of genetic information into haploid which is needed for the sexual reproduction of all diploid organisms

Ernest DuPraw- folded-fiber model

Chapter 3 Mendelian Genetics (book and ppt)

Transmission genetics- how genes are transmitted from parent to offspring 25% exhibited the contrasting trait

Mendel’s traits: Seed shape Seed colors Pod Shape Pod Color Flower Colors Flower position Stem height

Mendel’s Postulates: Unit Factors in Pairs- genetic characters are controlled by unit factors existing in pairs in individual organisms Dominance/Recessiveness- when two unlike unit factors responsible for a single character are present in a single individual, one unit factor is dominant to the other, which is said to be recessive Segregation- during the formation of gametes, the paired unit factors separate, or segregate, randomly so that each gamete receives one of the other with equal likelihood Independent Assortment- during gamete formation, segregating pairs of unit factors assort independently of each other

Reginald C. Punnett- devised the Punnett square The product law- the probability of two or more independent event occurring simultaneously is equal to the product of their individual probabilities

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Dr. Michael Rosbash, Dr Michael Young, and Dr. Jeffrey Hall - they discovered the period gene (PE) affecting circadian rhythm Period gene- biological clocks, responsible for secretion of melatonin

Autosomal Recessive Traits Albinism- synthesis of melanin pigment obstructed Sickle Cell Anemia- sickle shape red blood cells due to a mutation in the globin gene that encodes for the globin protein, block blood vessels, and cause early death Phenylketonuria- excess accumulation of phenylalanine in blood, mental retardation

Autosomal Dominant Achondroplasia- Brachydactyly- malformed hands with shortened fingers Nail Patella syndrome- causes change in the nails, elbows, kneecaps, and hip bone, missing or underdeveloped fingernails and toenails Huntington’s disease- progressive degeneration of a person’s physical and mental abilities, delayed into adulthood Marfan syndrome- affects skeletal system, the eyes, and cardiovascular system; tall and thin Familial Hypercholesterolemia- Heterozygotes have a defect in their receptors for low density lipoproteins (LDLs) – “bad cholesterol”

25% of affected individuals appear in families with no previous history of marfan syndrome; gene has a high mutation rate

FBN1- gene responsible for marfan syndrome Chromosome 15- where FBN1 is located Fibrillin- protein regulates growth, removes TGF beta TGF beta- protein that stimulates growth

In Marfan syndrome, mutant fibrillin produces defective connective tissue & excess TGF-beta accumulates, further weakening connective tissue.

As it leaves the heart, the aorta arches back & downward, feeding blood to all the major organ systems. Marfan syndrome weaken connective tissue around the base of the aorta causing it to enlarge and split open

Chapter 4 Non-Mendelian Genetics (ppt) Codominance- the joint coexpression of both allele in a heterozygote is called codominance

Tay-sachs rare inherited disorder that progressively destroys neurons in the brain and spinal cord, loss of motor skills Infants with Tay-sachs disease appear normal until the age of 3-6 Cherry red spot- characteristic Homozygous recessive are severely affect with lipid storage disorder (hoxosaminidase)

MN blood groups- characterized by an antigen called glycoproteins in the surface of RBCs Karl Kandsteiner- discovered ABO Blood groups Chromosome 9- where ABO is encoded Isoagglutinogen- another term for antigen

The Bombay Phenotype ( Blood type O) The A and B antigens are carbohydrate groups that are bound to lipid molecules on the surface of the RBCs H substance- precursor molecule where A and B antigens are derived from When the H substance is considered to be lacking or incompletely formed, blood type O is formed

Epistasis - Where the expression of one gene or gene pair masks or modifies the expression of another gene or gene pair

Thomas Hunt Morgan- recorded first case of X-linkage

Lesch-Nyhan Syndrome X-linked recessive disease Abnormal nucleic acid metabolism Accumulation of uric acid in blood and tissues, mental retardation

Penetrance- percentage of individuals who show at least some degree of expression of the mutant genotype Expressivity- reflect the range of expression of the mutant phenotype

Position Effect- the physical location of a gene in relation to other genetic material may influence its expression

** Organism’s phenotype is affected by expression of genes contained in DNA of mitochondria or chloroplasts rather than nucleus.**\

Why has analysis of inheritance patterns in chloroplasts and mitochondria been difficult? Function of organelles is dependent on gene products from both nuclear and organelle DNA, making discovery of genetic origin of mutation affecting organelles are difficult Many mitochondria & chloroplasts are contributed to each progeny.

Heteroplasmy – lead to normal cells since organelles lacking mutation provide the basis of wild-type function.

Karl Correns- provided earliest example of inheritance linked to chloroplast transmission

Poky- slowly growing mutant strain

2 reasons why mtDNA is vulnerable to mutations Ability to repair mtDNA damage does not appear to be equivalent to that of nuclear DNA Concentration of mutagenic free radicals generated by cell respiration that accumulate in mitochondria raises mutation rate in mtDNA

Myoclonic epilepsy & ragged-red fiber disease (MERRF) Maternally inherited Deafness, dementia, epilepsy, ataxia mutation in mitochondrial gene w/ mutant gene product w/c interfere w/ protein synthesis in mitochondria.

Many disorders in humans are due to mtDNA gene mutations. Mutagenic free radicals (carcinogens) generated by cell respiration accumulate in the mitochondria raising mutation rates of mtDNA.

Free radicals are unstable atoms that can damage cells, causing illness and aging.

A Genetics Perspective (ppt)

deCODE- biotech company to establish Health Sector Database (HSD) HSD- contains all medical records and genealogies of all residents in Iceland

Why establish a database in Iceland? Until 59 yrs ago, it has been almost completely isolated from outside immigration Plagues and volcanic eruptions also reduced genetic variation Small population

UK Biobank- Great Britain medical records database to search for disease-causing gene such as hypertension and heart disease

Genes- DNA sequences that encode for a functional protein or enzyme, also encodes for RNAs

Branches of Genetics Transmission genetics- experimental organisms and mating experiment to study transmission of traits Pedigree analysis- detailed family history to reconstruct the pattern followed by a traits as passes through generations Cytogenetics- studies chromosome number and structure Molecular genetics- uses recombinant DNA technology to identify, isolate, clone, and analyze genes Population genetics- how much genetic variation exists in populations (migration, population size, and natural selection)

Karyotypes- standardized arrangements of chromosome used to diagnose or to rule out genetic disorders

Francis Galton- proposed that natural selection should be used to improve the human species Hereditarianism- all human traits are determined only by genes Eugenics- selective breeding Emmanual Celler- changed faulty eugenics and immigration laws

Genetic testing - a type of medical test that identifies changes in chromosomes, genes, or proteins