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Transcript
Unit 1 Genetics 1.1 Cell Division Unicellular vs. Multicellular o Unicellular organisms: made of only one cell Ex. amoeba, paramecium, bacterium o Multicellular organisms: made of more than one cell Ex. butterfly, starfish, human Why Do Cells Divide? 1. To replace dead or worn out cells. 2. To stay small enough for efficient gas, nutrient and waste diffusion. 3. To enable an organism to grow and become multicellular. A totipotent cell (stem cell) divides and daughter cells specialize to perform one particular role in the body. How Do Cells Divide? Two forms of cell division: 1. Mitosis (Somatic Cell Division) o Most cells reproduce by mitosis. o Creates TWO genetically identical daughter cells from ONE parent cell. o Produces body (somatic) cells. Ex. skin cells, blood cells, root tip cells, etc. 2. Meiosis (Gametic Cell Division) o Creates FOUR genetically unique sex cells (gametes) Ex. sperm and egg o These gametes combine (fertilization) and the offspring are genetically different from the parents. o Gametes only produced in the gonads (sex organs) Ex. testes and ovaries 1.2 Somatic Cell Division o Each human somatic cell has 46 chromosomes. This is called the diploid number (2N) since there are 23 chromosomes from the father and 23 from the mother. o Two main parts of somatic cell division: interphase and mitosis Interphase o 95% of cell’s life during which it undergoes growth, repair, metabolism, and DNA replication. o Chromosomes are in stringy/tangled form known as chromatin o At the end of interphase, chromosomes (DNA) replicate to temporarily become 4N (ie. double the normal chromosome number, thus 92 instead of 46). o When chromosome replicates, the two identical copies remain attached to each other by the centromere, and the replicated chromosomes are now called chromatids. Mitosis 1) Prophase a. Early Prophase o Centrioles divide and move in pairs to opposite sides of nucleus o Microtubules begin to radiate from each centriole to form asters and spindle fibers o Chromosomes condense (thicken) and become visible as joined sister chromatids (genetically identical) b. Late Prophase o Chromosomes continue to condense o Spindle fibers attach to centromeres and begin to move chromatids to equatorial plate of the cell o Nucleolus and nuclear membrane begin to dissolve 2) Metaphase o Pairs of joined chromatids line up at the equator with spindle fivers originating from opposite poles of the cell o Nuclear membrane completely dissolves 3) Anaphase o Centromeres divide and former sister chromatids become daughter chromosomes, which are pulled to opposite poles by spindle fibers o An identical set of daughter chromosomes moves to each pole 4) Telophase o Nucleolus and nuclear membrane re-appear in each new daughter cell o Chromosomes de-condense (unwind) to become chromatin again o Two genetically identical cells have been produced and both are diploid (2N) with respect to chromosome number (thus, 46) Cytokinesis o Immediate after mitosis, cell membrane pinches in at the equator (called furrowing) to divide the cytoplasm so that two separate daughter cells are formed 1.3 Cloning Cloning o Cloning is the process of forming identical offspring (clone) using the genetic material of a single donor cell or tissue. o Biotechnology: the field of biology that involves the use of living things in engineering, industry and medicine. It includes cloning plants for use in agriculture. Plant Cloning o First plant cloning occurred in 1958 with a carrot cell. o The process of remarkable in that the mature, specialized carrot cells were used. These cells were returned to undifferentiated state before cloning. Animal Cloning o In 1996, Dolly, a sheep, was the first mammal to be cloned o An adult body cell was used for the cloning process, and this is significant in that it was challenging to stimulate a body cell to restart the process of growth and differentiation. o In adult cells, the nuclear material has changed so that a nucleus will normally not develop into an entire organism because the cells are too specialized. o When adult cells are starved of nutrients, they begin to act like unspecialized cells of an embryo. This is how the scientists cloned Dolly. Cloning a Frog 1. Remove nucleus from an unfertilized egg cell using a micropipette to form an enucleated egg (recipient). 2. Remove nucleus from a somatic cell of a separate frog (donor) and insert it into the enucleated egg cell. 3. Egg cell with new nucleus divides by mitosis to form a blastula (embryo). 4. The blastula grows into a cloned frog with identical genetic material to the original donor. Cloning a White Mouse 1. Obtain embryonic cell from a WHITE mouse (donor). 2. Extract WHITE mouse nucleus to clone. 3. Obtain unfertilized egg from BROWN mouse (recipient) and remove nucleus (enucleate it). 4. Insert WHITE nucleus into BRWON enucleated unfertilized egg. 5. After cells divide, implant embryo into BROWN mouse’s uterus (surrogate). 6. BRWON surrogate mouse gives birth to a cloned WHITE mouse that is genetically identical to donor. Therapeutic Cloning 1. 2. 3. 4. Extract nucleus of healthy starved adult somatic cell from patient. Insert patient nucleus into enucleated human egg cell. Grow cells to embryo state (stem cells). Separate stem cells and grow complete tissue or organ. (ex. heart, kidney, spinal-cord, etc.) 5. Insert tissue or organ back into patient with no rejection problems, since the somatic cell was from the patient. 1.4 Meiosis (Gametogenesis) Introduction o Meiosis is the process by which sex cells (gametes) are formed in gonads (ex. ovaries and testes). o In meiosis, the chromosome number of gametes is half that of the parent cell, thus 23 in humans. This is called the haploid chromosome number (1N). o Offspring carry genetic information from each of the parents. The paired chromosomes (23 from father and 23 from mother) are called homologous chromosomes. The homologous chromosomes are similar in size, shape, and gene arrangement. The genes in homologous chromosomes deal with the same trait. o Each body cell (not sex cells) contains 23 pairs of homologous chromosomes in total. They interact during meiosis, and your characteristics are determined by the manner in which genes from homologous chromosomes interact. o Alleles: similar forms of a gene. Stages of Meiosis o Meiosis involves 2 nuclear division that produce 4 haploid cells. o Meiosis I is often called reduction division, because the diploid number is reduced to the haploid number of chromosomes. o Meiosis II is marked by separation of two chromatids. o As in mitosis, the DNA replicates before meiosis in interphase. 1) Meiosis I a. Prophase I o Nuclear membrane begins to dissolve o Centriole splits and itsparts move to opposite poles within the cell o Spindle fibers are formed o Chromosomes come together in homologous pairs. Each chromosome of the pair is a homologue and is composed of a pair of sister chromatids. The whole structure (2 homologues) is called a tetrad because there are 4 chromatids in total. o Synapsis: the process of pairing up of homologues. o Crossing over: the intertwined chromatids from different homologues breaking and exchanging segment (ie. genetic material) b. Metaphase I o Homologous chromosomes attach themselves to spindle fibers and line up along the equatorial plate c. Anaphase I o Segregation/Independent assortment: the homologous chromosomes move toward opposite poles. o Reduction division: one member of each homologous pair will be found in each of the new cells. Each chromosome consists of 2 sister chromatids. d. Telophase I o Membrane begins to form around each nucleus. o Unlike in mitosis, the chromosomes in the two nuclei are not identical and do not carry exactly the same information. 2) Meiosis II * No replication of the chromosomes prior to meiosis II a. Prophase II o Beginning of second division. o Nuclear membrane dissolves and spindle fibers begin to form. b. Metaphase II o Chromosomes, each with two chromatids, line up along the equatorial plate. o The chromatids remain pinned together by the centromere. c. Anaphase II o The attachment between the two chromatids break and they move to the opposite poles. o Nuclear membrane begins for form around the chromatids, which are now daughter chromosomes. d. Telophase II o Second nuclear division is completed and the second division of cytoplasm (cytokinesis) occurs. o 4 haploid daughter cells are produced from each meiotic division. o The genetic diversity in the offspring is an advantage of sexual reproduction. This diversity was caused by: Crossing-over: changed chromatids Segregation/Independent assortment of chromatids to daughter cells (random assortment) More on Meiosis o A zygote (fertilized egg) forms from the fusion of male and female gametes. In humans, it has the diploid # of 46 chromosomes (23 from sperm cell and 23 from egg cell). o Spermatogensis: type of meiosis that produces sperm cells. Occurs in seminiferous tubules in the testes. Produces 4 haploid sperm cells (each genetically unique) o Oogenesis: type of meiosis that produces egg cells. Produces only 1 haploid egg cell Other egg cells are called polar bodies and they die since most of their cytoplasm was contributed to the one surviving egg cell (ovum; oocytes after first division, ootids after second division, and the surviving one is specifically called an ovum). Sex Chromosomes o Humans have 46 chromosomes, or 23 pairs. 44 of these (ie. 22 pairs) are autosomes. Two (ie. 1 pair) are sex chromosomes. o Females posses 2 X chromosomes, and males posses 1 X and 1 Y chromosomes in their somatic cells. o In gametes, there is only 1 sex chromosome (no other chromosomes). Egg cells have an X, and sperm cells have an X or a Y. o Union of X-bearing egg and X-bearing sperm produce a female. Union of X-bearing egg and Y-bearing sperm produce a male. o Thus, the gender of an offspring depends on the sex chromosome possessed by the sperm. 1.5 Karyotypes Karyotypes o Karyotype: a special chart in which all of the chromosomes are photographed, cut out, and then paired up in homologous pairs. o Homologous chromosomes can be paired this way because they are similar in size, shape, and (gene) banding patterns. o This chart allows some chromosomal genetic disorders to be easily visualized. o Chromosomal disorders occur when chromosomes do not separate properly during meiosis so that a sperm or egg cell has more or less than the normal number of chromosomes. Amniocentesis o A syringe is inserted into the amniotic sac and some amniotic fluid is removed. This fluid contains some cells that have been shed by the baby. Preparing a Karyotype o The baby’s cells are broken apart and spun in a centrifuge which separates the nucleus from other organelles. o The nucleus is then examined and chromosomes are photographed, cut out, and arranged in order of size, shape and banding patterns into 4 rows. The sex chromosomes are last. Gorilla and Rat Karyotype o Karyotypes of other animals can also be prepared. They have different number of chromosomes compared to humans. o Gorillas (apes) have more and rats have less than we do. Abnormal Human Karyotype o Many abnormal karyotypes show more or less than the proper number of chromosomes. o Causes of abnormal karyotypes: 1) Non-Disjunction Disorders Chromosomes don’t properly separate into daughter cells Gametes receive more or less chromosomes than normal 2) Chromosome Breaks A piece of the chromosome is lost (deletion mutation) Piece may attach to another chromosome (addition mutation) Down Syndrome (Trisomy 21) o There is an extra chromosome #21. This is a trisomy since there are 3 chromosomes instead of 2. o The individuals with this syndrome may be male or female, and they have a round, full face; enlarged and creased tongue; short height; large forehead; and usually some degree of mental retardation. o A non-disjunction disorder Edward’s Syndrome (Trisomy 18) o There is an extra chromosome #18 o Life expectancy is about 10 weeks o A non-disjunction disorder Patau’s Syndrome (Trisomy 13) o o o o There is an extra chromosome #13 Individuals with this syndrome have small, non-functioning eyes Survive only a few weeks after birth A non-disjunction disorder Klinefelter’s Syndrome (Trisomy XXY) o There is an extra X chromosome (2 X chromosomes and 1 Y chromosome). o This is a trisomy since there are 3 chromosomes instead of 2. o The individuals with this syndrome appear male at birth, but as they enter sexual maturity, they begin producing high levels of female sex hormones and are sterile. They have small testes, low sperm, and breast development. o A non-disjunction disorder Turner’s Syndrome (Monosomy X0) o There is missing sex chromosome (no sex chromosome on the egg cell; X chromosome on the sperm cell). The resulting zygote is written as X0 (where 0 means lacking a chromosome). o This is a monosomy since there is 1 chromosome instead of 2. o The individuals with this syndrome appear female but do not usually develop sexually (sterile) and tend to be short and have thick, wide necks. o A non-disjunction disorder 1.6 Chromosomes, Genes and DNA o A chromosome is essentially a single DNA molecule. Thus, human somatic cells have 46 DNA molecules. o DNA stands for “deoxyribonucleic acid”, which describes the type of sugar (deoxyribose) and the location in the cell (nucleus). o The building blocks of DNA are nucleotides which are attached together like a twisted ladder to form a double helix. o Each nucleotide has three parts: Phosphate group Deoxyribose sugar Nitrogenous base o There are four kinds of nitrogenous bases, so there are four different kinds of nucleotides: A = Adenine G = Guanine C = Cytosine T = Thymine o A and G are purines, meaning their bases have two rings, and C and T are pyrimidines, meaning their bases have one ring. o The sugars and phosphate groups are on the outside of the molecule, forming the sugarphosphate backbone. Each sugar is attached to the phosphate below it by a covalent bond. o The bases project into the middle and the base on one strand attaches to the base on the other strand by 2 or 3 hydrogen bonds. o The nitrogenous bases do not bond randomly. o A bonds with T, and C bonds with G (written as A-T and C-G). o This is called complementary base pairing since the bases must fit properly together in order to bond. o The order of these bases along the DNA is what makes up the genetic code. o Any change in the order of these bases causes a genetic mutation. o Gene: a stretch of DNA with enough bases to code for one trait (ex. eye colour). o You have two copies of each gene, one on each homologous chromosome. o Alleles: alternate forms of a gene (ex. curly hair vs. straight hair genes). o Chromosome mapping: scientists know the location and function of many genes on the chromosomes o Gene therapy: it will eventually be possible to remove dysfunctional genes and insert healthy ones. This could lead to designer babies, which is choosing the genes for your baby. DNA Replication (Semi-conservative replication) o DNA replication occurs in interphase, in the nucleus. Step 1: o Helicase enzyme breaks the hydrogen bonds between the bases on opposite strands and separates the DNA molecule into two halves. o Both halves now have unpaired nucleotides, which sets the stage for construction of two identical DNA molecules. Step 2: o DNA Polymerase enzyme (“polymer” means a long strand of something) attaches new complementary nucleotides (which come from what you eat and which stay in the nucleus) to the unpaired bases on each separated strand, following the rule of complementary base pairing. o For every A (Adenine) that the enzyme encounters, it attaches a T (Thymine) and for every G (Guanine), it attaches a C (Cytosine). Step 3: o Ligase enzyme creates a bond between the sugar of a newly added nucleotide and the phosphate of another nucleotide (ie. re-joins the sugar-phosphate backbone). o Now two identical DNA molecules (or chromosomes) remain. 1.7 Mendelian Genetics Gregor Mendel o An Austrian monk known as the father of genetics. o He experimented with pea plants, which is a very simple organism. He looked at traits such as: Round vs. wrinkled seeds Tall vs. short plants Green vs. yellow seeds o He did not know about cells, chromosomes or genes. But, he believed there were “factors” (now known as genes/alleles) that caused inheritance but didn’t know what exactly. Mendel’s Experiments o He “crossed” pure breeding tall pea plants with pure breeding short (dwarf) pea plants. He expected intermediate in height of the offspring, but all the offspring were tall. o He the crossed pure breeding round seeded plants with pure breeding wrinkled seeded plants. All offspring were round, with no intermediate. o Mendel believed that some heritable traits were “dominant” and some were “recessive”. Punnett Square o The way to represent the inheritance of dominant and recessive traits: CAPITAL LETTER = dominant (ex. T = tall) lowercase letter = recessive (ex. t = short) o Mendel also believed, through experiments, that factors were inherited in pairs, ie. 2 or each. (Now, we know there are homologous chromosomes with each carrying an allele.): Homozygous = two of the same factor (ex. TT) Heterozygous = two different factors (ex. Tt) o Punnett, Mendel’s friend, came up with a mathematical way to represent the cross – the Punnett Square. o Example of a cross: Pure breeding (homozygous) tall plant = TT t t Pure breeding (homozygous) short plant = tt The cross is written as: TT x tt (x means “crossed with”) T Tt Tt T Tt Tt o o o o o The dominant T masks the recessive t, and thus, all the offspring would show the dominant trait of tall. All the offspring are heterozygous. Offspring are called the F1 generation (1st generation) compared to the parents. Crossing two F1 generation seeds produce F2 generation offspring. Phenotype: the outward appearance of expression of a trait (ex. round, tall) Genotype: the actual genes (factors) causing the phenotype (ex. RR, Tt) Example: T t t t Tt tt Tt tt - Phenotype ratio of offspring = 1 tall : 1 short - Genotype ratio of offspring = 1 Tt : 1 tt (*always reduce ratios to lowest) Test Cross o o o o To determine an unknown genotype, you cross it with a known genotype. The only way to know for sure is crossing with homozygous recessive. Then, find the possible offspring by test crossand work backwards. Example: A farmer wants to know if his prize cow is homozygous for black spots or heterozygous. Black spots is dominant. He has both spotted and non-spotted cattle but this one is special. How can he figure this out? B = spots B – x bb b = no spots Phenotype of Test Cross: b b B Bb Bb – b– b– If – = B: All offspring cattle will have spots The prize cow is BB (homozygous) If – = b: 50% of offspring cattle will have spots The prize cow is Bb (heterozygous) Dihybrid Cross o Dihybrid cross: a genetic cross between individuals with different alleles for two genes T = tall, t = short, R = round, r =wrinkled TtRr x ttRr tR tr tR tr TR TtRR TtRr TtRR TtRr Tr TtRr Ttrr TtRr Ttrr tR ttRR ttRr ttRR ttRr tr ttRr Ttrr ttRr ttrr Phenotype ratio: 6 tall-round: 2 tall-wrinkled: 6 short-round: 2 short-wrinkled *reduce: 3 tall-round: 1 tall-wrinkled: 3 short-round: 1 short-wrinkled Types of Dominance 1) Complete Dominance o Only one allele is expressed and the other is completely recessive (ex. Tt = tall plant) 2) Incomplete Dominance a) Co-dominance o Both alleles are expressed at the same time in the offspring (ex. roan hair colour in bull, the blood type) o Ex. H – hair HrHr x HwHw HrHw red hair white hair red & white hairs (roan – not a blend) b) Intermediate Inheritance o Both alleles are expressed, but at different times in the offspring, leading to a blending effect (ex. snapdragon flower colour) o Ex. C – colour CRCR x CwCw CRCW red white pink (blend) o When you cross 2 of CRCW, you get 3 different phenotypes 1.8 Blood Type Genetics Theory o Human blood type is caused by the presence of glycoproteins (sugar proteins) which are embedded in the cell membrane of red blood cells (RBC’s). o Two genes on homologous chromosomes determine the blood type. o Blood type is inherited as simple dominant or recessive genes. The gene that causes type A blood is dominant over that causing type O blood. But, gene that causes type B blood is equally dominant to that causing type A blood. Thus, genes for A and B are called codominant. Blood Types o For blood transfusions, knowing the blood type of a patient is critical, as the blood received can be rejected and attacked by the patient’s immune system. o The glycoproteins on RBC’s act as antigens which stimulate an immune response that leads to destruction of the RBC’s, which can block blood vessels (agglutination/clumping). Antibodies attack the glycoproteins. Anti-A (antibody A) attacks glycoproteins on type A blood, anti-B attacks glycoproteins on type B blood, both the anti-A and anti-B attack glycoproteins on type AB blood, and no antibodies attack type O blood since there is no glycoproteins to attack. o Four major blood types: A, B, AB and O. Phenotype Genotype Antibodies Made Type A (dominant) IA– (IAIA or IAi) Anti-B ---< Diagram (Red Blood Cell) A Anti-A ---< A A A B Type B (dominant) IB– (I I or IBi) B B Anti-A ---< Anti-B ---< B B B AB Type AB (codominant) A B I I Neither Anti-A or Anti-B >--- Anti-B Anti-A ---< AB AB AB *No glycoproteins to be attacked Type O (recessive) ii Anti-A ---< Anti-B ---< *Normally, you do not make antibodies against your own glycoproteins, because then the antibodies with attack your glycoproteins. Blood Transfusions o When RBC’s from a donor are not the same type as those of the recipient (receiver), the recipient’s immune system attacks them. o The white blood cells (WBC’s), specifically called lymphocytes, produce Y-shaped proteins called antibodies which are like tiny missiles that attack the glycoproteins (antigens) on RBC cell membrane. B WBC Lymphocyte B antigen RBC B Antibody B B o Only certain blood types can be donated to certain recipients. Donor Recipient A B AB A – + + B + – + AB – – – O + + + * Type O is the “universal donor” (can be given to any blood type). * Type AB is the “universal recipient” (can receive from any blood type). O – – – – 1.9 Sex-Linked Genes and Disorders Introduction o Human females (symbol = ) are written as XX. o Human males (symbol = ♂ ) are written as XY. Sex-Linked Disorders Sex Chromosomes XX XY XXX X0 Phenotype Normal female Normal male Triple X, female, decreased IQ, tall Turner’s, male, short height, thick wide neck Klinefelter’s, male, female sex hormones, small XXY testes, low sperm, breast development XYY “Super male” syndrome, more aggression Y0 dies o Sex chromosomes contain genes that code for traits such as production of female sex hormones (estrogen) and male sex hormones (testosterone). They also carry genetic disorders such as hemophilia (blood fails to clot properly), colour blindness, high blood pressure (hyper tension) and muscular dystrophy. Hemophilia (recessive sex-linked disorder) Normal female: XHXH Normal male: XHY Carrier female: XHXh No carrier male Hemophilic female: XhXh Hemophilic male: XhY o The sex-linked genes are carried by the X chromosome and not by the Y chromosome. o Since male only has one X chromosome, if there is a disorder on that X chromosome, Y chromosome has nothing to mask it. o Female can carry a disordered gene on one X chromosome but still have a normal gene on the other X chromosome to mask it. o A “carrier female” usually doesn’t suffer from the disorder, but she carries it and may pass it on to her children, usually to her sons. A carrier female will suffer from a disorder if that disorder is dominant. For hemophilia, which is a recessive disorder, carriers will not suffer. 1.10 Pedigrees – Tracking Inheritance o For determining the patterns of inheritance of genes that are beneficial or detrimental to human health. It helps in predicting how a certain gene will be passed on to future generations. Pedigree Charts o Pedigree: a diagram of an individual’s ancestors used in human genetics to analyze the Mendelian inheritance of a certain trait; also used for selective breeding of plants and animals. It’s a chart that traces the inheritance of a certain trait among members of a family. Shows the connections between parents and offspring, the sex of individuals, and the presence of absence of a trait. o Symbols: Normal male Affected male Mating Normal female Siblings Identical twins Affected female Carrier female Fraternal twins o Each generation is identified by Roman numerals and Arabic numerals (what we use) symbolize individuals within a given generation. o Birth order of offspring drawn from left to right (oldest to youngest) I 1 2 II 1 2 3 4 5 III 1 2 3 Sex Linkage – Following the X and Y Chromosomes o Autosomal inheritance: inheritance of alleles located on autosomal (non-sex) chromosomes Both males and females are affected equally, since there is no difference between the autosomes of males and that of females. o Sex-linked: describes an allele that is found on one of the sex chromosomes, X or Y, and is expressed when passed on to offspring o X-linked: phenotypic expression of an allele that is found on the X chromosome. If a male inherits X chromosome from a recessive allele carrier mother, he will express the disorder because Y chromosome cannot mask it. The male cannot inherit X-linked disorder from father, since a father passes on a Y chromosome to a son. A female must inherit 2 copies of recessive gene – one on each X chromosome – in order to express the disorder (If she inherited only one recessive allele, the other X can mask it.) Examples of X-linked inheritance: hemophilia A, red-green colour blindness, male-pattern baldness, etc. o Y-linked: phenotypic expression of an allele that is found on the Y chromosome Passed on from father to son There are fewer Y-linked disorders than X-linked ones because the Y chromosome is small and doesn’t carry as much genetic information. Ex. reduced fertility in males