BIS101 Lec 1

BIS101-001: Genes and Gene Expression!
Welcome to BIS101-001 Spring 2014 Genes and Gene Expression R.L. Rodriguez Instructor, Mon - Wed 10:00 a.m. - 11:50 a.m. 3 Kleiber Hall Introductory Lecture #1
BIS101-001, Spring 2014Genes and Gene Expression, R.L. Rodriguez 2014 1
BIS101: Genes and Gene Expression: Introduction!
!!BIS101 is a survey of the fundamental concepts of genetics and molecular biology including vocabulary, technology, experiment design, with particular emphasis on gene structure and function. Prokaryotic and eukaryotic molecular models will be used to demonstrate basic principles of gene mapping, chromatin structure, genomics, replication, transcription, translation, mutations, repair, gene regulation and genetic engineering.
BIS101-001, Spring 2014Genes and Gene Expression, R.L. Rodriguez 2014
!!Textbook: Genetic Analysis: An Integrative Approach, Sanders and Bowman, 1st Ed. !!Grade based on 500 points distributed among two midterms, each worth 100 points, 100 points in online assignments and a final exam worth 200 points. !!Final exam is cumulative: approx. 50% (100 points) from the first two midterms and 50% (100 points) based on new material. !!Requests for regrades must be submitted to the Teaching Assistants using a Petition for Regrade Form obtained on SmartSite. No midterms regraded after the final and no regrading of final exams
!!There are no early, late or makeup exams. A valid medical excuse is the only basis for missing an exam or for petitioning for an incomplete (I) grade. In the case of missed midterm exams, the final exam will be weighted an additional 100 points. Sixty (60) minutes are allotted to each midterm exam. !!Past grade distribution is approx. as follows: 18% As, 33% Bs, 29% Cs, 10% Ds and 8% Fs. !!Zero tolerance for cheating
BIS101: MasteringGenetics!
!! MasteringGenetics is an online, interactive, problemsolving program designed expressly for use with the textbook. !! Four MasteringGenetics assignments are required during the quarter. The required assignments you complete will be graded and submitted through Mastering. The program provides feedback and hints for wrong answers and uses automated grading to record your assignment scores. !! You can register for MasteringGenetics by going to: MasterGenetics.com. Using the course code: \MGENRODRIGUEZ78592, you can access class assignments.
Why Genes, Gene Expression and Genomes?!
!!Course objective: To understand the true relationship between genotype and phenotype. !!Definition of Genotype: The actual alleles (alternation forms of a gene, or sequence of DNA) in an individual. !!Definition of Phenotype: An observable characteristic (produced by the genotype). !!Challenge: The path from genotype to phenotype is not linear!
6 BIS101-001, Spring 2014Genes and Gene Expression, R.L. Rodriguez 2014
Filters of Genetic Potential
PHENOTYPE
GENOTYPE
Life span Because of these gene modifiers, we do not have to be slaves to our genes nor do we have to be victims of genetic determinism.
BIS101-01 Spring 2014Genes and Gene Expression, R.L. Rodriguez 2014 7
BIS101-001 Genes and Gene Expression
Mendels Principles: Meiosis, Chromosomes and Probabilities (Review: Chapter 2)
Achieving Integrated Genetic Fluency (IGF)
Mendels Laws Probability & Statistics Chromosome, DNA Behavior Prediction

(Pedigree Analysis)
You should be here.
Chapter 1: The Study of Biological Information!
!!The information fundamental of life is encoded in DNA. !!Biological function emerges primarily from the expressed forms of DNA (e.g., RNA and protein). !!All life forms are part of a vast network of related individuals. !!The modular nature of the genome facilitates rapid evolution !!Powerful analytical tools and method of scientific inquiry (p. 27), permit the dissection of the genetic complexity for the good of humankind
10
This Lecture: Mendel and Chromosomes!
!!Mendels 1st and 2nd Laws of Inheritance. !!Definitions !!Using crosses to infer the nature of inheritance. !!Test Crosses and recessive traits !!Mitosis and Meiosis. !!Mendelian inheritance and Chromosome Theory !!Cell cycle and chromosome replication !!Product and Sum Rules !!Application of Product and Sum Rules in genetic crosses.
Chapter 2 Vocabulary
!! !! !! !! !! !! !! !! !! !! !! !! !! !! !! !! !! !! !! !! Allele: An alternate form of the same gene, (e.g., the seed color gene in peas can be yellow or green). Character: Any specific, true-breeding property of an organism. Synonymous with "trait or "phenotype." Dihybrid Cross: A cross between two individuals with different alleles at two gene loci. A dihybrid is a heterozygous individual with different alleles at two gene loci. Diploid: A eukaryote cell or organism having two sets of chromosomes (or a pair of genes at each locus). Dominant: An allele or trait that expresses its phenotype when heterozygous with a recessive allele, (e.g., A is dominant to a because the phenotypes AA and Aa are the same). Eukaryote: An organism or cell containing two sets of genes (diploid) for each character, where the entire genetic complement is contained within a well-defined nucleus. Prokaryotes are 1N and have no defined nucleus (e.g.,bacteria) F1: First filial generation. The progeny of a cross between two parental types that differ in one or more genes. Gene: The basic unit of heredity that occupies a fixed chromosomal location (locus). The gene contains the information for tRNAs, rRNAs and mRNA (i.e., proteins). Genotype: The specific allelic composition of a cell or set of genes. Haploid: A cell or organism having only one set of chromosomes (i.e., one gene at each locus or haploid). Gamete: A haploid reproductive cell such as a sperm (or pollen) and egg (or ova). Heterozygous: A diploid with dissimilar alleles at one or more loci and therefore not true-breeding for the trait(s)at that locus or loci. Homozygous: A diploid having the same allele at a given locus, therefore, true-breeding for the trait at that locus. Locus: The region along the length of a chromosome where the alleles (pair of genes) for a particular trait resides. Monohybrid Cross: A cross between two individuals with different alleles at one gene locus. A monohybrid is a heterozygous individual with different alleles at one gene locus. N: The haploid chromosome number. Prokaryotes are 1N while most eukaryotes are 2N. Phenotype: The detectable outward biochemical or morphological manifestation of a specific genotype. The form a character or trait takes in a specific individual. Punnett Square: A cross-multiplication table used for determining the expected genetic outcomes of a mating. Recessive: An allele or trait that does not express its phenotype in the heterozygous condition (e.g., a is recessive to A when the phenotype of Aa is the same as AA). Testcross: A cross between an F1 individual (unknown genotype) and the homozygous recessive parent of the F1, the "tester." Because the genotype of the tester is known, the test cross reveals the genotype of the F1. BIS101-001, Spring 2014Genes and Gene Expression, R.L. Rodriguez 2014 12
Patterns of Inheritance: Main Concepts

!! The existence of genes can be inferred by observing standard ratios in the progeny of mating between two different phenotypes !! Discrete phenotypic differences in a trait can sometimes be due to differences in a single gene !! Each type of gene is represented twice in each cell, one on each member of a chromosome pair. !! Inheritance patterns are based on chromosome behavior at meiosis !! During gamete formation, each member of a gene pair segregate producing two types of gametes !! In gamete formation, gene pairs on different chromosome pairs behave independently of one another (unless theyre linked).
Inference and Integrated Genetic Fluency (IGF)
Inference: the act or process of reaching a conclusion about something from known facts or evidence.
14
Ancient inferences about genetics
The Talmud made an ahead-of-its-time observation that inferred the existence of X-linked genes. The authors of the Talmud ruled that if a woman bears two sons who die of bleeding after circumcision, any additional sons that she has, should not be circumcised. They further state that the sons of her sister must not be circumcised, whereas her brothers sons should be circumcised, (passed from the mother to her sons). reflecting a clear understanding that this is a disease..
Milestones of Modern Genetics!
!!1853 Mendel begins pea breeding experiments (p. 26-27)

Mendel's First Law (p.30): The Principle of Equal Segregation. During the formation of gametes, the paired characters (alleles) segregate (or separate) equally so that half of the gametes receive one allele and half of the gametes receive the other member of the pair. Mendel's Five Assumptions (p.35): (1) Hereditary determinants (genes) are particulate in nature (therefore there is no blending of characters). (2) Each adult pea plant has a pair of genes (alleles) for each character (as can be seen in the F1, one member can be dominant and one recessive) (3) Members of each gene pair segregate equally into the gametes (pollen/ovule, sperm/egg) (4) Consequently, each gamete carries one member of each gene pair (5) The union of gametes from each parent (to form the zygote) is random.
16
Mendels 1st Law: Segregation of yellow (Y), green (y)!

Parents Gametes YY Y only Yy zygote x yy y only Points 1&2 Points 4
1st Filial Generation (F1)
Ovule produced 1/2Y 1/2Y Pollen produced 1/2y 1/4YY 1/4Yy 1/2y 1/4Yy 1/4yy
Points 3
Points 5
Overall F2 Genotypic Ratio 1YY : 2Yy : 1yy, or 3:1 Phenotypic ratio

Mendels Experimental System (Fig. 2.1)
!!Mendels Seven True Breeding Characters
18
Pea Hybridization Techniques: Monohybrid Cross

pollen placed on stigma
!!Monohybrid Cross of peas with purple and white flowers (p.28)
anthers removed
purple
white
F1 All purple
19
Dominance and Recessive Traits (p.33)
!! The dominance or recessive nature of a character, trait or gene can be revealed by a test cross involving the F1 and the homozygous recessive parent. !! Test crosses typically give 1:1 ratios for a monohybrid cross involving a recessive trait.
20
Mendels strong inference based on large numbers

!! Counting traits from his monohybrid crosses, Mendel inferred his 3:1 ratio, predicted by his Law of Equal Segregation.
During the formation of gametes, the paired characters (alleles) segregate (or separate) equally so that half of the gametes receive one allele and half of the gametes receive the other member of the pair (p.32).
Mendels Second Law (p.35)

!! Independent Assortment: Gene pairs on separate chromosomes pairs, assort themselves independently at meiosis. !! This can be seen from a dihybrid cross between two different characters (seed shape and seed color) on different chromosomes. !! 9:3:3:1 ratios are always characteristic of a dihybrid cross.
22
Mendels Law of Independent Assortment (p.80)
!!In the case of the 9:3:3:1 ratio produced from a dihybrid cross, Mendel discovered that what looked like an exception to the 3:1 ratio was in fact, a mixture of two 3:1 ratios. !!In the case of two characters, the members of both pairs of alleles assort themselves independently into gametes. The 16 genotypes shown on the next slide can be broken down into 12:4 round to wrinkled phenotypes and 12:4 yellow to green phenotypes. In both instance we can see a 3:1 ratio.
23
Dihybrid Cross (2 monohybrid crosses) (Fig. 2.11)
!!The result of a dihybrid cross are simply the combination of two, monohybrid crosses !!In this example, the ratio of round to wrinkled seeds is 12:4 or 3:1.
24
Dihybrid Cross (2 monohybrid crosses) (Fig. 2.11)
!!The result of a dihybrid cross are simply the combination of two, monohybrid crosses !!In this example, the ratio of yellow to green seeds is 12:4 or 3:1.
25
Law of Independent Assortment: Summary
!!Although undiscovered for nearly 40 years, Mendel's experiments laid the foundation for all future genetic analysis, molecular biology and the revolutions in gene cloning and genomics. His work made it possible to infer the existence and nature of hereditary material without ever seeing it; and predict how they will appear in the offspring. !!M endels Laws of Equal Segregation and Independent Assortment anticipated what would later be found by microscopic observation in the nuclei of cells and summarized in the Chromosome Theory of Inheritance.
Mendels Second Law

!! Mendels Law of Independent Assortment is also known as interchromosomal recombination and is observed when dominant and recessive gene pairs are located on separate chromosomes pairs or unlinked. !! As with the monohybrid cross, a test cross can be use to demonstrate the presence of recessive alleles in the F1 progeny
Dihybrid Test Cross (p. 38-40)

!! Mendels crosses always produced an F1 that looked like only one of the two parents. For example, in the monohybrid cross RR x rr, the F1 progeny Rr looks like the round parent. The test cross can be used to reveal the presence of the recessive allele in the F1. The test cross always involves crossing the F1 progeny with the homozygous recessive parent. For a monohybrid cross, the test cross progeny exhibit a 1:1 ratio of Rr and rr. In the dihybrid cross shown above, a 1:1:1:1 ratio of RrYy; Rryy; rrYy; rryy
RY ry
Ry
rY
ry
RrYy Rryy rrYy rryy 1 : 1 : 1 : 1
(these ratios occur only with unlinked genes)

Mendels Laws and Chromosome Behavior

(Pedigree Analysis)
29
Chromosome Behavior (mitosis-meiosis) (Ch. 3)

Cytokinesis
!!The dihybrid cross reflects the behavior of chromosomes during meiosis. Chromosome mechanics during mitosis and meiosis was unknown to Mendel.
Interphase Prophase Prometaphase Metaphase
Telophase
Anaphase
30
Summary of Chromosome Behavior (p. 74)
Mitosis
Meiosis
31
Chromosomes Duplication
Chromosome duplication and S-phase = DNA replication

Review of Chromosomes During Mitosis (p.70)
33
Review of Chromosomes During Meiosis (p.74)
34
Comparison of Mitosis and Meiosis:10 Points (p.73-79)

1.! The products of mitosis are two daughter cells, each 2N. The products of meiosis are four ga metes, each 1N. 2.! During mitosis N goes from 2N to 4N to 2N as a result of 1 replication or S phase and 1 cell division. In meiosis, N goes from 2N to 4N to 2N to 1N as a result of 1 replication or S phase but 2 cell division cycles. 3.! Unlike mitotic prophase, the separate chromosomes of meiosis zygotene prophase I are not distributed throughout the nucleus but paired into bivalents (paired homologs). The number of bivalents seen in this stage equal the haploid number of the organism. 4.! There is no pairing of homologous chromosomes in mitosis. In meiosis pairing of homologous chromosomes starts in zygotene and becomes visible in pachytene. 5.! In meiosis, the homologous chromosome pairs align themselves at the metaphase plate of metaphase I while in mitosis, chromosomes align at the metaphase plate separately, not in pairs.
Comparison of Mitosis and Meiosis (p.73-79)

6.! In mitosis, centromeres divide at anaphase, In meiosis, centromeres divide during anaphase II, not anaphase I. 7.! S phase in cells about to undergo meiosis is longer than for mitosis. In the newt, Triturus, it takes 12 hours to go through S prior to mitosis while it takes 10 days in pre-meiotic cells. 8.! In meiosis, the fibers coming from the centrosomes attach to the two sister chromatids of each chromosome are pulled toward the same pole in meiosis. In mitosis, fibers attached to each centromere for each chromatid are oriented to opposite poles. 9.! Prophase I of meiosis is much longer than prophase of mitosis. Depending on the organism, the pachytene and diplotene stages of prophase I may last weeks or years depending on the organism. 10.! Crossing over during the pachytene stage of prophase I of meiosis can result in some exchanges of genetic material between homologs.
Chromosome Theory of Inheritance (p.81)

!!Chromosome continuity. The chromosomes one observes during one metaphase are exactly the same as those observed in the next metaphase (in the nucleus of the daughter cell). !!During mitosis and meiosis, chromosomes divide along the length of the chromosomes. !!The pairing between chromosomes during prophase of meiosis is specific, not random. !!Chromosome individuality. Different chromosome pairs are qualitatively different (i.e., carry different genes). !!During meiosis, different chromosome pairs assort themselves independently (Mendel's dihybrid cross).
!!A pair of characters (like those described in Mendels dihybrid cross) can assort themselves independently during anaphase I of meiosis.
!!1902: Sutton and Boveri propose the chromosome theory of inheritance.

37
Independent Assortment and Meiosis

R r R
R Y
r Y
Independent Assortment (Interchromosomal Recombination)
(p.80; Fig. 3.14)

Mendels Laws and Probabilities/Statistics (p.35-38)

(Pedigree Analysis)
40
Mendels Cross Reveals a Probabilistic Reality
!!The Punnett square at the left is just a graphical representation of probabilistic outcomes for different genotypes and phenotypes. !! The utility of Punnett squares breaks down, however, with the addition of each new trait to the cross (e.g., monhydrid = 4 squares, dihybrids = 16 squares, trihybrids = 64 squares or (2n)2 where n = the number of traits in the cross).
Mendels Cross Reveals a Statistical Reality (p. 44-45)
!!According to Mendels Laws, the segregation of alleles into gametes are independent events. !!Therefore, since the union of gametes is random, predicting the outcome for progeny can be determined using the product rule and the sum rule.
Product and Sum Rule (p.44-45)
!! The product rule states that the probability of independent events occurring together is the product of the probabilities of the individual events themselves (also called the and rule). !! The sum rule states that the probability of either of two mutually exclusive events occurring is the sum of their individual probabilities (also called the or rule). !! The product rule is useful for calculating the expected frequency of a particular genotype while the sum rule is useful in calculating the expected frequency of a phenotype.
43
Product Rule (p.44)
!! The possible outcomes of rolling dice follow the product rule because the outcome on each separate die is independent of the others. For example, the probability of rolling a pair of 4s is calculate based on the probability of rolling one 4 on one die, which is 1/6 (because the die has six sides and only one side carries the 4). This probability is written as follows:
p (of a 4) = 1/6
!! Therefore the probability of rolling a pair of 4s can be written:

p (of two 4s) = 1/6 x 1/6 = 1/36
The product rule deals with one independent event and another independent event occurring together (4 and 4).
Sum Rule
!! The sum rule deals with the probability of one mutually exclusive event or another occurring (A or B). In other words, either of the two outcomes satisfies the condition of the probability question. We have already determined that the probability of two 4s is 1/36. By the same way we can use the product rule to calculate that the probability of two 5s is also 1/36 (1/6 x 1/6). !! Now we can calculate the probability of either two 4s or two 5s occurring. Because these outcomes are mutually exclusive, the sum rule tell us that the probability of two 4s or two 5s is 1/18 (1/36 + 1/36). This probability can be written as:
p (of two 4s or two 5s) = 1/36 + 1/36 = 1/18
!! As you can see, the sum rule states that the probability of either of two mutually exclusive events occuring is the sum of their individual probabilities.
Mendels Cross Reveals a Statistical Reality

!! F1 RrYy (round, yellow) !! Gametes: RY; Ry; rY; ry
p of R = 1/2 p of r = 1/2 p of Y = 1/2 p of y = 1/2 p of RY = 1/2 x 1/2 = 1/4 p of Ry = 1/2 x 1/2 = 1/4 p of ry = 1/2 x 1/2 = 1/4 p of rY = 1/2 x 1/2 = 1/4 Predicting frequency if RYRY genotype in F2: RYRY = 1/4 x 1/4 = 1/16 (1/2 x 1/2 x 1/2 x 1/2 = 1/16)
Mendels Cross Reveals a Statistical Reality

!! F1 RrYy (round, yellow) !! Gametes: RY; Ry; rY; ry
p of R = 1/2 p of r = 1/2 p of Y = 1/2 p of y = 1/2 p of RY = 1/2 x 1/2 = 1/4 p of Ry = 1/2 x 1/2 = 1/4 p of ry = 1/2 x 1/2 = 1/4 p of rY = 1/2 x 1/2 = 1/4 Predicting frequency wrinkled phenotype (rr--) in F2: 1/16 + 1/16 + 1/16 + 1/16 = 1/4
Product Rule Example

!! To create at homozygous tester plant line for five traits, a researcher had to make the following cross:
A /a ; b /b ; C /c ; D /d ; E /e X
A /a ; B /b ; C /c ; d /d ; E /e
What is the probability of finding a plant with the following genotype:
a /a ; b /b ; c /c ; d /d ; e /e A/a x A/a ! a/a = 1/4 b/b x B/b ! b/b = 1/2 C/c x C/c ! c/c = 1/4 D/d x d/d ! d/d = 1/2 E/e x E/e ! e/e = 1/4
Product/Sum Rules
Product Rule = 1/256

The researcher will need a minimum of 256 progeny to get 1 homozygous plant at all 5 loci.
This Lecture: Mendel and Chromosomes!
!! Mendels 1st and 2nd Laws of Inheritance. !! Definitions !! Using crosses to infer the nature of inheritance. !! Test Crosses and recessive traits !! Mitosis and Meiosis. !! Mendelian inheritance and Chromosome Theory !! Cell cycle and chromosome replication !! Product and Sum Rules !! Application of Product and Sum Rules in genetic crosses.
49
Achieving Integrated Genetic Fluency (IGF)

(Pedigree Analysis)
You should be here.
50

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BIS101-001: Genes and Gene Expression!

BIS101: Genes and Gene Expression: Introduction!

BIS101-001, Spring 2014Genes and Gene Expression, R.L. Rodriguez 2014

BIS101: Genes and Gene Expression: Introduction!

BIS101: Genes and Gene Expression: Introduction!

BIS101-001, Spring 2014Genes and Gene Expression, R.L. Rodriguez 2014

Why Genes, Gene Expression and Genomes?!

Filters of Genetic Potential

BIS101-001 Genes and Gene Expression

Mendels Principles: Meiosis, Chromosomes and Probabilities (Review: Chapter 2)

BIS101-001, Spring 2014Genes and Gene Expression, R.L. Rodriguez 2014

Achieving Integrated Genetic Fluency (IGF)

Mendels Laws Probability & Statistics Chromosome, DNA Behavior Prediction

You should be here.

BIS101-001, Spring 2014Genes and Gene Expression, R.L. Rodriguez 2014

Chapter 1: The Study of Biological Information!

BIS101-001, Spring 2014Genes and Gene Expression, R.L. Rodriguez 2014

This Lecture: Mendel and Chromosomes!

Patterns of Inheritance: Main Concepts

Inference and Integrated Genetic Fluency (IGF)

BIS101-001, Spring 2014Genes and Gene Expression, R.L. Rodriguez 2014

Ancient inferences about genetics

Milestones of Modern Genetics!

!!1853 Mendel begins pea breeding experiments (p. 26-27)

BIS101-001, Spring 2014Genes and Gene Expression, R.L. Rodriguez 2014

Mendels 1st Law: Segregation of yellow (Y), green (y)!

1st Filial Generation (F1)

Overall F2 Genotypic Ratio 1YY : 2Yy : 1yy, or 3:1 Phenotypic ratio

Mendels Experimental System (Fig. 2.1)

!!Mendels Seven True Breeding Characters

BIS101-001, Spring 2014Genes and Gene Expression, R.L. Rodriguez 2014

Pea Hybridization Techniques: Monohybrid Cross

!!Monohybrid Cross of peas with purple and white flowers (p.28)

BIS101-001, Spring 2014Genes and Gene Expression, R.L. Rodriguez 2014

Dominance and Recessive Traits (p.33)

BIS101-001, Spring 2014Genes and Gene Expression, R.L. Rodriguez 2014

Mendels strong inference based on large numbers

Mendels Second Law (p.35)

BIS101-001, Spring 2014Genes and Gene Expression, R.L. Rodriguez 2014

Mendels Law of Independent Assortment (p.80)

BIS101-001, Spring 2014Genes and Gene Expression, R.L. Rodriguez 2014

Dihybrid Cross (2 monohybrid crosses) (Fig. 2.11)

BIS101-001, Spring 2014Genes and Gene Expression, R.L. Rodriguez 2014

Dihybrid Cross (2 monohybrid crosses) (Fig. 2.11)

BIS101-001, Spring 2014Genes and Gene Expression, R.L. Rodriguez 2014

Law of Independent Assortment: Summary

Mendels Second Law

Dihybrid Test Cross (p. 38-40)

RrYy Rryy rrYy rryy 1 : 1 : 1 : 1

(these ratios occur only with unlinked genes)

Mendels Laws and Chromosome Behavior

Mendels Laws Probability & Statistics Chromosome, DNA Behavior Prediction

BIS101-001, Spring 2014Genes and Gene Expression, R.L. Rodriguez 2014

Chromosome Behavior (mitosis-meiosis) (Ch. 3)

BIS101-001, Spring 2014Genes and Gene Expression, R.L. Rodriguez 2014

Summary of Chromosome Behavior (p. 74)

BIS101-001, Spring 2014Genes and Gene Expression, R.L. Rodriguez 2014

Chromosome duplication and S-phase = DNA replication

Review of Chromosomes During Mitosis (p.70)

BIS101-001, Spring 2014Genes and Gene Expression, R.L. Rodriguez 2014

Review of Chromosomes During Meiosis (p.74)

BIS101-001, Spring 2014Genes and Gene Expression, R.L. Rodriguez 2014

Comparison of Mitosis and Meiosis:10 Points (p.73-79)