Chromosome Theory of Inheritance Chapter 4 PDF

Chromosome Theory of Inheritance 3& Chapter 4  I. Key Concepts A. Two means of Cell Division: 1. Mitosis – Nuclear division that generates two daughter cells – Chromosome number maintained All somatic cells derived from the same species conta...

Chromosome Theory of Inheritance 3& Chapter 4  I. Key Concepts A. Two means of Cell Division: 1. Mitosis – Nuclear division that generates two daughter cells – Chromosome number maintained All somatic cells derived from the same species contain an identical number of chromosomes – Development, growth, and repair 2. Meiosis- – Nuclear division that generates gametes (egg and sperm) Germ cells are precursors to gametes – Sexual reproduction B. Diploid versus haploid: 2n versus n 1. Most body cells (somatic cells) are diploid (2n) -each chromosome pair has one maternal and one paternal copy 2. Meiosis à haploid (n) gametes – half chromosome number 3. Two gametes fuse during fertilization to form a zygote. (2n) 4. In Drosophila, 2n = 8, n = 4 5. In humans , 2n = 46 and n = 23 II. Chromosome Structure A. Chromosomes can be classified by centromere position Humans contain no telocentric chromosomes B. Terminology 1. Sister chromatids identical copies of a replicated chromosome 2. Homologs( *homologous chromosomes ) contain the same set of genes, but can have different alleles for some genes 3. Nonhomologs carry completely unrelated sets of genes 4. Karyotype: Micrograph of stained chromosomes arranged in homologous pairs Autosomes Sex chromosomes – In humans, presence or absence of Y chromosome determines gender àXY male, XX female SRY gene III. The Cell Cycle of Eukaryotes A. a way of looking at entire lifespan of a cell, continuous alternation division- non- division B. Two basic parts 1. Interphase a. normal state of the cell (growth, metabolism, func) 2. M Phase (Mitosis or Meiosis)  C. Overview of the Cycle 1. G1 Phase* (gap I) – active metabolism; cell usually grows in size - restriction pt- cell commits to cell division 2. S Phase* – cell replicates it DNA 3. G2 Phase* (gap II) – active metabolism cell grows slightly bigger 4. M Phase – nucleus and cell divides Mitosis :(1)karyokinesis nuclear division (1 à 2 nuclei) (2)Cytokinesis – cytoplasmic division (1 à 2 c 5. G0 a. Late in G1, all cells follow one of two paths: 1. they withdraw from cell cycle and become dormant in G0 2. they become committed to DNA synthesis, cell cycle. b. G0- viable and metabolically active, but NO proliferation Time spent in each phase varies between cell types E. Movement of the Chromosomes 1. Structure a. chromatids b. centromere highly constricted region of the DNA, sister chromatids are in close contact c. kinetochore: protein unit that provides the attachment points for spindle fibers  Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Cohesin Chromatid proteins Centromere region of chromosome Kinetochore Kinetochore microtubules Metaphase chromosome 15 2. Mitotic Spindle - Organize & sort chromosomes through mitosis - Formed from microtubule organizing centers (MTOC’s) at centrosomes (2 centrioles lay at right angles to each other) -3 types of microtubles in animal cell mitotic spindle: 1. aster- outward from centriole to membrane 2. polar-between the 2 poles 3. kinetochore microtubules- attach to the kinetochore F. Phase of Mitotic Cell Division Recall, cell first goes through Interphase Prophase (Prometaphase) Metaphase Anaphase Telophase 1. Prophase a. Nuclear envelope breaks down b. Chromosomes become visible. c. Sister chromatids are connected at the centromere 2. Prometaphase a. Chromosomes are clearly double structures b. Centrioles reach opposite poles c. Spindle fibers form** d. Spindle fibers attach to centromeres -kinetochore 3. Metaphase Chromosomes align on metaphase (equatorial) plate  4. Anaphase a. Removal of cohesin proteins causes centromeres to separate b. Kinetochore microtubules shorten and pull separated sister chromatids to opposite poles (characteristic V shape) 5. Telophase a. Spindle fibers disappear b. Centrioles return to normal positioning c. Uncoiling of chromosomes d. Reformation of nuclear env. 6. Cytokinesis a. Division of the cytoplasm b. Two identical daughter cells are produced c. Differs in plant & animal -cell plate vs cleavage furrow (Constriction of actin) d. Does not have to occur in all cells of all organisms - multinucleated tissue Figure 3.9  F. Cell Cycle Regulation A variety of checkpoints ensure that cell is able to move from one phase to another 1. G1 checkpoint * (committed to division after) - cell size, molecular signals such as GF, DNA integrity 2. G2 checkpoint - DNA integrity, checks replication 3. M checkpoint (spindle) - (post metaphase) looks that all the sister chromatids are correctly attached to the spindle microtubules. 4. Cyclin- dependent kinases a. act as master control molecules b. advance the cell from one stage of the cell cycle to next c. CDKs only function when associated with proteins called Cyclins d. form CDK-cyclin complexes >phosphorylate other proteins that perform functions at certain times in cell cycle Phosphorylation can activate or inactive a protein e. different ones appear at specific times in cycle  G. Meiotic Cell Division *more complicated than mitosis 1. Basic cell cycle is the same (interphase) but m phase is now meiosis 2. Key points: Two divisions 1:4 cell division Produces haploid gametes from germ cells Meiosis I is a reductional division, Meiosis II is an equational division DNA synthesis occurs before the beginning of meiosis I but does not occur again before meiosis II.  Overview of meiosis Two rounds of cell division Chromosomes duplicate once; nuclei divide twice Meiosis I reduces the chromosomes from 2n to n. Meiosis I 1. Prophase I Substages (Fig 4.15) i. Leptotene (Leptonema)-Chromatin condenses into very thin chromosomes ii. Zygotene (Zygonema) - Homolog search and recognition. Synapsis begins (synaptonemal complex) iii. Pachytene(Pachynema)-Tetrad, crossing over >recombination nodules appear Homolog pairing during meiosis I forms a tetrad Crossing Over  Prophase I substages continued.. iv. Diplotene (Diplonema) - Chiasma (chiasmata pl) remains >Section that results from crossing over - Tetrad begins to pull apart slightly v. Diakinesis - Nuclear env. fragmentation & Synaptonemal complex disappears 2. Metaphase I - Independent assortment of nonhomologs 3. Anaphase I -homologs move to opposite sides (One half of each tetrad ) >disjunction (note the centromeres holding sister chromatids do not divide) 4. Telophase I and cytokinesis >2 haploid cells at end of MI Interkinesis  Overview of important concepts in meiosis I Homologs pair, cross over, and then segregate Sister chromatids remain intact throughout meiosis I Maternal and paternal homologs recombine and create new combinations of alleles After recombination, homologs segregate to different daughter cells Meiosis II 1. Prophase II- each dyad composed of sister chromatids 2. Metaphase II- metaphase plate 3. Anaphase II- the sister chromatids in each dyad are separated to opposite poles. 4. Telophase II- one member of each pair of homologous chromosomes at each pole. (monad) 5. Cytokinesis, ends with 4 non- identical *** haploid cells Meiosis contributes to genetic diversity in two ways Independent assortment of nonhomologs creates different combinations of alleles Crossing-over between homologs creates different combinations of alleles within each chromosome Chromosome number abnormalities occurs due to non-disjunction in Meiosis G. Meiosis vs Mitosis H. Gametogenesis *The development of the gametes varies amongst males and females (other animals have variations of this process) 1. Male gametes are produced by spermatogenesis in the testes 2. Female gametes are produced by oogenesis in the ovary.  1. Spermatogenesis Diploid Spermatogonium (germ cells in the testes) –> divide by mitosis to form Primary spermatocyteà After puberty: Undergoes Meiosis Ià 2 Secondary spermatocyteà Undergoes Meiosis II à Spermatids à Developmental changes occur àmature into Spermatozoa (mobile sperm) >Equal numbers of X and Y sperm are produced 2. Oogenesis Oogonium (germ cells in the ovaries) –> divide by mitosis to form à primary oocyte begin Meiosis I à (arrested at prophase I (diplotene) until puberty) àSecondary oocyte (and 1st polar body*) Ovulation occurs, one egg released each month in cases of fertilization: sperm fuses with egg, as sperm nucleus is traveling to egg nucleus now Meiosis IIà develops into 1 ovum * (and 2nd polar body*) >Cytoplasm is not divided equally. -Cell that receives the most cytoplasm undergoes both meiosis I and II and develops into the ovum. - polar bodies do not undergo further division. IV. Variation in Chromosome Structure and Number A. Aneuploidy in Humans Variations in chromosome number, an organism gains or loses one or more chromosomes (other than an exact multiple of the haploid set) 1. Monosomy – loss of a single chromosome 2n-1 Ex. Turner Syndrome 2. Trisomy- gain of a single chromosome 2n + 1 a. 3 copies of one chromosome are present, so pairing configurations are usually irregular. only 2 of 3 homologs may synapse b. sex chromosomes have less dramatic phenotype than autosomes, which are often lethal. (1) XXX, (2) Klinefelters XXY, (3) Jacobs XYY, c. Ex. Trisomy 21 Down syndrome d. Only two other trisomy syndromes have been observed -Patau (13) & Edwards syndrome (18) -only a 5% chance of surviving > 1 yr. e. Trisomies are often found in spontaneously aborted fetuses  Trisomy Down syndrome – 90% of cases, the additional chromosome comes from the mother's egg. – most common genetic disorder caused by a chromosomal abnormality. – occasionally runs in familiesà familial Down syndrome (different) B. These abnormalities occurs due to non-disjunction in Meiosis V. Influence of Sex on Mendelian Inheritance Patterns A. Sex-linked genes -those found on one of the two types of sex chromosomes, but not both 1. X-linked (recessive or dominant) – Many human disorders including hemophilia and colorblindness Males are more likely to be affected.. Why? Hemizygous 2. Y-linked (holandric) Rare, relatively few genes in humans – Transmitted from father to son Example(1) The Drosophila white gene Example: Hemophilia in humans 1. X-linked recessive trait that causes the blood to clot improperly 2. H = normal allele and h = hemophilia allele 3. the following genotypes/phenotypes are possible: XH XH normal female, XH Xh- normal female, Xh Xh hemophilic woman, XH Y normal male, and Xh Y hemophilic male *notice only one copy of the allele is needed to cause the disorder in males 4. Example: A hemophiliac man has a daughter with the normal phenotype. She marries a man who is also normal for the trait. What are the genotypes of everyone involved? What is the probability that the couple will have a hemophiliac child? Hemolphilic man: Xh Y (only possibility) Daughter: could be XH XH or XH Xh- but since her father can only pass her the Xh allele she must be XH Xh daughters husband: XH Y Probability is 25% (hemophilic son is only possiblity) Example of an X-linked trait in humans (Top) View of the world to a person with normal color vision (Bottom) View of the world to a person with red-green colorblindness Color deficit simulation courtesy of Vischeck (www.vischeck.com). Source image courtesy of NASA B. Mammalian cells count their X chromosomes and allow only one of them to remain active >Dosage Compensation 1. In normal human females, one X is inactivated. > During inactivation, the DNA becomes highly compacted Most genes on the inactivated X cannot be expressed 2. This highly condensed X can be seen in the interphase nuclei of somatic cells = Barr body a. When this inactivated X is replicated during cell division- Both copies remain highly compacted and inactive and X inactivation is passed along to all future somatic cells b. results in genetic mosaics Ex. Calico cat Ex. In humans: Red green color blindness Only one X chr. remains active in Mammalian cells n Additional X chromosomes are converted to Barr bodies Sex Chromosome Number of Phenotype Composition Barr bodies Normal female XX 1 Normal male XY 0 Turner syndrome (female) X0 0 Triple X syndrome (female) XXX 2 Klinefelter syndrome (male) XXY 1 Dosage compensation in mammals Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Barr body © Courtesy of I. Solovei, University of Munich (LMU). © Tim Davis / Photo Researchers (a) Nucleus with a Barr body (b) A calico cat The black and orange mosaic pattern is due to The Barr body in a human nucleus an X-linked gene that can occur as an orange or black allele Figure 5.3  C.Sex-limited inheritance occurs in cases where the expression of a specific phenotype is absolutely limited to one sex. Genotype Female Male Phenotype Phenotype HH Hen-feathered Hen-feathered Hh Hen-feathered Hen-feathered hh Hen-feathered Cock- feathered D. sex-influenced inheritance the sex of an individual influences the expression of a phenotype that is not limited to one sex or the other. Genotype Female Male Phenotype Phenotype BB Bald Bald Bb Not bald Bald bb Not bald Not bald