Notes
The Genetics Method of Reasoning (Logic) of Genetics
**8 elements of genetic reasoning --Purpose: to figure out how genetics operates through systematic observation and experimentation --Questions: What can be figured out? --Information: Facts that can be systematically gathered about genetics --Interpretation & Inference: Judgments based on observations and experimentation that lead to systematic knowledge --Concepts: Working of genetics as predictable and understandable --Assumptions: There are laws at work in genetics that can be figured out through systematic observations and experimentations --Implications & consequences: Study=knowledge --Point of View: Genetics can be understood **Basic or Applied Research --Basic: Experiments done to gain understanding of phenomenon. May not lead to applications. Fuels more basic research. --Applied: Experiments done to overcome problems. Knowledge gained from basic research used. **Agri--Plant/Animal improvement **Medicine--Genetic disease, diagnostic tests, pharmaceuticals --Not always a sharp dividing line between the two.
Chapter One: Introduction to Genetics
I. Genetics? --Heredity--cause of similarities between individuals **storage of genetic info **transfer of genetic info **expression of genetic info --Variation--cause/occurrence of differences between individuals
--Genetics attempts to explain mechanism/basis for similarities/differences between related individuals II. Divisions of Genetics --Transmission **parentsoffspring --Population **Genetic composition of populations and how collective genes change through time. --Molecular **Study of chemical nature of genetic info and how it is encoded, replicated, and expressed at molecular level. III. Albinism in the Hopis --autosomal recessive trait --reduced pigment --visual impairment --increased rate of skin cancer Incidence of Albinism Population Hopi Indians N.A. Caucasians --Why so common in Hopis? **Place of Albinism in Culture **Albinism=Special Status **Positions of Leadership --Men with Albinism **Normally farm--increased sun **Albino men exempt **mate and spread genes more IV. Importance of Genetics Incidence 1 in 200 1 in 40,000
--Appearance, health, intelligence, personality --Agriculture --Pharmaceutical industry --Medicine --Biotechnology V. Importance of Genetics to Biology --Foundation of many fields --Techniques used in biological research
History of Genetics
VI. Genetics is both old and new --Wilhelm Johannsen [1857-1927] **Suggested Mendel's "factors" be called "genes" --William Bateson [1861-1926] **study of mechanism be called "genetics" **First to hold office in area of genetics in 1908 VII. Mechanisms of Heredity --Development of ideas replete with misconceptions, many nave --Historically theories (ideas) may be roughly divided into three categories **vapors and fluids **preformation **particulate VIII. Developments in Genetics --Plant/Animal Domestication **First plants/animals domesticated 10-12,000 years ago **Early domestication in Middle East --sheep, goats, dogs --wheat, barley, peas, lentils **In China--rice and millet by 7000 ybp
**In Central America--corn by 4000 ybp **Initial stages--artificial selection **Speed of domestication indicates early humans understood heredity --Greeks **Pangenesis --heredity information located in different body parts --particles (gemmules) carry info to reproduction organs **Germplasm theory [today] --each cell contains a complete set of genetic info **Inheritance of Acquired Characteristics --traits acquired during lifetime are passed to children --Romans **Techniques of plant and animal breeding --Origins of Modern Genetics **Microscopy--Hooke and van Leeuwenhoek **Preformationism --All life exists preformed in egg or sperm called the homunculus **ovists--said homunculus in egg **spermists--homunculus in sperm --Traits inherited from one parent --Rejected through study of development **Blending Inheritance --Offspring inherit a blend of parental traits **Early Plant Hybridizers --Grew [1641-1712]--identified plant reproductive structures --Kolreuter [1733-1806]--studied heredity --Mendel--discovered basics of heredity **Cell biology
--discovery of cell nucleus [1831] --cell theory [1840] --mitosis [1879] --recognition that nucleus was site of heredity [1884-85] IX. Birth of Modern Genetics --Discovery of Mendel's work [1900] --Applications of Mendel's principles --First human genetics [Garrod, 1910] --Drosophila genetics **Morgan and students **Golden Age of Genetics [1920s-1940s] --Population genetics [1930s] **Sewall Wright, Fisher, Haldane --Biochemical genetics [30s-40s] **Beadle and Tatum --Bacterial and Viral genetics --Watson and Crick **discovered structure of DNA [1953] --Rise of molecular genetics --Recombinant DNA [1973] --Human gene therapy [1990] --Rough draft of human genome [2000] --Analysis of Human Genome [2001] X. Qualities of Useful Organisms for Genetic Research --The genetic history of the organism is well known --Short life cycle --Large number of offspring --Easy to handle
--Variation must exist between individuals in population --Controlled matings --Ease of biochemical analysis XI. Basic Concepts in Genetics --Cells are either prokaryotes or eukaryotes --The gene is the fundamental unit of heredity --Multiple forms called alleles --Genes encode phenotypes **G+E+T=P *G=genotype *E=environment --micro --mega *T=time *P=phenotype **"GET phenotype" --Genetic information is carried in DNA & RNA --Genes are located on chromosomes **Separate in mitosis and meiosis --Genetic information is transferred from DNARNAprotein **Central dogma --Mutations are permanent, heritable changes in genetic info. **gene mutations **chromosome mutations --Some traits are affected by multiple factors **multiple genes [polygenic] **environment **multifactoral
--genes [intrinsic factors+environment] --Evolution is genetic change **genetic variation **selection + or -
Chapter Two: Chromosomes & Cellular Reproduction
I. Two Different Kinds of Cells [See table 2.1] --Prokaryotic **unicellular **no nucleus or organelles --Eukaryotic **Uni or multicellular **membrane-bound organelles **compartmentalized --Archaea have some genetic features in common with eukaryotes. II. Cell Reproduction --Cell division in bacteria [fig. 2.5] **single circular chromosome **nucleoid region --Cell cycle in eukaryotes **mitosis=nuclear division=karyokinesis **cytokinesis=division of cytoplasm III. Why Chromosomes? --Terminology **Univalent=unpaired chromosome **Bivalent=paired chromosome **Dyad=2 chromatids of one chromosome **Tetrad=4 chromatids of any bivalent --Chromosomes
A) Functional pairs of a eukaryotic chromosome --centromere **kinetochore --telomeres --origin of replication B) Duplication of Chromosomes --sister chromatids C) Homologous Chromosomes --in diploid [2n] individuals --contain info for same traits D) Counting Chromosomes & DNA molecules --Number of chromosomes=number of functional centromeres --Number of DNA molecules=Number of chromatids --Stages of Cell Cycle [fig. 2.9] A) Interphase --G1 (gap 1)=cell growth --G0=nondividing stage (ex. Neurons) --S (synthesis)=DNA synthesis --G2 (gap 2)=cell prepares for division B) M-phase (Mitosis) --Prophase **chromosomes condense **spindle forms outside of nucleus --Prometaphase **Nuclear membrane breaks down **Spindle fibers attach to chromosomes **Chromosomes move --congression
--Metaphase **Chromsomes line up on metaphase plate --Anaphase **Sister chromatids separate --each becomes a chromosome **Chromosomes move toward poles [fig 2.11] --Telophase **Chromosomes arrive at spindle poles **chromosomes relax **Nuclear membrane reforms --Cytokinesis --Results of Mitosis and Cell Cycle **1 cell divides into 2 cells (usually) **no reduction of chromosome number **daughter cells genetically identical --Cell cycle control **checkpoints [fig. 2.13] --G1/S --G2/M --Spindle-assembly **Cyclins & CDKs **See animation of cell cycle http://www.whfreeman.com/pierce **A --Practice cell has 8 chromosomes in G1. How many chromosomes and DNA molecules per cell at each stage? a) Metaphase b) Anaphase c) After cytokinesis IV. Meiosis 8 16 8 16 16 8
--Sexual Reproduction **Gametogenesis--meiosis--reduction in chromosome number --spermatogenesis--production of male gamete **oogenesis--production of oocytes **Fertilization--fusion of gametes --Two Divisions [fig 2.15] **Reduction division--chromosome number reduced by half 2nn **Equational division--similar to mitosis --Stages of Meiosis A) Interphase --cell growth and development --G1, S, G2 substages --DNA synthesis B) Prophase I 1) Leptotene: chromosomes condense throughout Prophase I Chromosomes become invisible 2) Zygotene: homologous chromosomes pair 3) Pachytene: synapsis occurs Synaptonemal complex occurs Completion of crossing over and exchange of genetic info between nonsister chromatids 4) Diplotene: homologs separate; remain connected at chiasmata [points of crossing-over] 5) Diakinesis: chiasmata to ends of chromosomes [terminalization] Nuclear membrane breaks down Spindle forms Summary: chromosomes contract, homologs pair, crossing-over, spindle forms C) Metaphase I
--Homologous pairs line up on metaphase plate D) Anaphase I --Homologous chromosomes separate, move toward poles. E) Telophase I --chromosomes arrive at poles --cytokinesis F) Interkinesis (Interphase) --Does not occur in all organisms --No DNA replication --Spindle breaks down --Chromosomes relax --Nuclear membrane reforms G) Prophase II (only if interkinesis) --Chromosomes condense --Nuclear membrane breaks down --Spindle reforms H) Metaphase II --chromosomes line up I) Anaphase II --chromatids separate --chromosomes move toward poles J) Telophase II --chromosomes arrive at poles --cytokinesis
Chapter 4 Notes
"Sex Determination and Sex-Linked Characteristics"
I.
Sex Determination What are the fundamental differences between males and females? Size of gametes a. Sex Differences i. Monoecious--"one house"--both male and female ex. Flower ii. Dioecious--"two houses"--separate sexes ex. Humans b. Sex-Determining Systems i. Chromosomes 1. XX, XY system a. Female XX homogametic sex b. Male XY heterogametic sex 2. XX, X0 system a. Female XX homogametic b. Male X0 heterogametic 3. ZZ, ZW system a. Male ZZ [XX] homogametic b. Female ZW [XY] heterogametic 4. Haplodiploidy a. Female diploid [2n]--develops from fertilized egg b. Male haploid [n]--develops from unfertilized egg ex. Bees [fig. 4.6] ii. Genetic Sex Determination--sex determined by genes on undifferentiated chromosomes. Ex. Some plants. iii. Environmental Sex Determination [see 4.7 and above paragraph] c. Sex Determination in Drosophila and Humans i. Both have XX, XY ii. Sex of Drosophila determined by sex ratio 1. X--autosome ratio 2. See table 4.1 iii. Sex Determination in Humans 1. SRY gene [sex-determining region of Y] a. Stimulates gonadstestes b. Testes secrete testosterone which stimulates Mulerianinhibiting substance c. Induce male structures, inhibit female structures 2. Anomalies of Sexual Development a. Klinefelter Syndrome i. XXY, XXYY, XXXY ii. 1 in 1000 male births 1. Normal male genitals 2. Small testes
3. Slight breast development 4. Some mental impairment b. Turner Syndrome i. X0 ii. 1 in 3000 female births 1. Short stature 2. Broad chest 3. Webbing of neck 4. Underdevelopment of secondary female characteristics 5. Usually sterile c. Poly-X Female i. XXX, XXXX, XXXXX ii. 1 in 1000 female births 1. Normal female characteristics 2. Many sterile 3. Some mental impairment with increasing X's d. Androgen Insensitivity Syndrome i. XY 1. External female characteristics 2. No ovaries or uterus 3. Testes present in abdominal cavity 4. Elevated levels of testosterone 5. Defect in androgen receptor 6. X-linked recessive trait e. XYY syndrome i. XYY--male ii. Usually tall [over 6' in height] iii. Used to be linked with criminality, but has been disproven. f. True Hermaphroditism i. Some XX, Some XY ii. Most probably XX-XY mosaics iii. External phenotype variable, often genitals ambiguous iv. Both male and female gonads 3. Conclusion a. At least one X required for development b. One Y sufficient to produce male phenotype c. Absence of Y results in female phenotype d. Fertility genes located on X and Y e. Extra Xs upset normal development in both males and females f. The more Xs, the more severe developmental and mental problems g. See Table 4.1--will be on test or quiz
Chapter 4,5,6ish Notes
I. Human Genetics
II.
III.
a. Pedigree--see Table 6.1 and 6.2 "need to learn" b. Be sure to know about: i. Twin studies ii. Adoption studies iii. Genetic counseling iv. Genetic testing Linked Genes and Recombination a. Linked genes do not assort independently b. Occur in same linkage group or chromosome i. Human females--23 linkage groups ii. Human males--24 linkage groups c. Inheritance of Two-Linked Genes in Tomatoes i. Linkage with no crossing-over ii. Independent assortment iii. Linkage with crossing-over See examples for each d. Recombination Frequency--Number of Recom/total number X 100 i. Each time crossing-over occurs half of gametes will be recombinants ii. Recombination frequency= crossing-over frequency iii. Generally, RF may be less b/c some recombinants may go undetected iv. Maximum recombination frequency= 50% e. Coupling & Repulsion i. Genes in coupling are called cis A B/a b ii. Genes in repulsion are called trans A b/a B f. Determining Progeny Number With Linked Genes i. See Example g. Crossing-Over and Genetic Maps i. Distance between genes is proportional to RF ii. 1% recombination=1 map unit iii. 1 map unit=1 centimorgan h. Creating Genetic Maps i. Three Point Cross i. Testcross involving 3 linked genes ii. Gene mapping iii. Distances between gens proportional to RF See Example iv. Coefficient of coincidence=observed double crossovers/expected double crossovers v. Interference=1-CC vi. Mapping With Three-Point Crosses 1. Determine order of genes 2. Determine map distances between genes 3. Calculate CC & interference vii. See example Problems Sex-Linked Traits Extensions of Mendelian Genetics a. Sex-Linked Traits i. Located on sex chromosomes
1. Y-linked traits and X-linked traits 2. Incomplete Sex Linkage ii. Y-linked Traits [holandric traits] 1. Few traits 2. Only occur in males 3. Fatherall sons iii. X-linked Traits 1. Males and females 2. Many traits 3. Males--hemizgous 4. Males receive X from mother, females from mother and father 5. Criss-Cross pattern of inheritance a. Fatherdaughtergrandson iv. Incomplete [Partial] Sex-Linkage 1. Rare phenomenon of gene having loci on homologous segments of both X & Y chromosomes 2. Recombination v. Pseudoautosomal Regions 1. Pair during synapsis vi. Example of X-linked recessive trait-red/green colorblindness in humans 1. Females a. XcXc--colorblind b. XcX+--normal [See Fig. 4.5] 2. Males a. XcY--colorblind b. X+Y--normal vii. Reciprocal crosses allow you to determine whether a trait is sex-linked. b. Dosage Compensation i. Only one X chromosome expressed in each cell of female mammals ii. Random; set early in development iii. Mosaic XAXa--some cells express A, others express a iv. Tortoiseshell cat See Fig 4.17 and 1. X+ black 2. Xo orange Table 4.2 3. X+Xo tortoiseshell barr body--inactivated X chromosomes One less barr body than X c. What is the difference between incomplete and codominance? i. Incomplete=intermediate of two traits ii. Codominant=both traits expressed d. Multiple Alleles i. Allelic Series 1. Observed in populations 2. Only 2 alleles in 2n individuals 3. Number of possible genotypes a. n=number of possible alleles b. [n(n+1)]/2 ii. ABO blood Group
1. Ia, Ib, i a. Ia>i b. Ib>i c. Ia=Ib>i iii. Practice 1. Sally has blood type A. She has a child with blood type A. What are the possible blood types of the father? a. A, B, AB, O b. Sally: Ia_ c. Child could be IaIa, Iai d. Father must contribute Ia or I allele, so he could be IaIa, Iai, IaIb, Ibi, ii