lecture 1

Life Science 4-1 Introduction to Genetics

Instructor Brent Bill, Ph.D.

Email: [email protected]

• Office Hours

• Monday 3:30-4:30 in Lakretz 101

• Tuesday 9:00-10:00 in Terasaki Life Sciences 1000

• Friday at 11:00-12:00 in Gonda building room 2303

mailto:[email protected]

TA’s• Bella Haruty

• Rekha Singh

• Xiao Song

• Kevin Wang

Life Science Core

Life Science Core Education Of2ice Hershey Hall, Room 222 (310) 825-‐6614 [email protected]

mailto:[email protected]

Materials• Textbook: Genetics: From Genes to

Genomes, Fourth Edition by Hartwell et al. (2011).

• Optional, but highly suggested: Study Guide/Solution Manual and interactive genetics CD-ROM and handbook.

• Optional: Interactive Genetics, Johnson and Merriam, 2004. Problem book, and CD.

This is a fast paced course, and covers a lot of material in a short time. It is your responsibility to keep up with the pace by doing

the readings and solving all assigned problem sets.

Grading• Exam 1 Monday, July 7, 2014 100pts

• Exam 2 Monday, July 21, 2014 100pts

• Final Friday, August 1, 2014 200pts

• Discussion 50pts

• 450 points based on a normal curve.

Exam Review Sessions

• July 2, 3:30-5:00

• July 18, 2:00-3:30

• July 30, 3:30-5:00

• All sessions in Humanities A51 (Lecture Hall)

Genetics

• The Science of Heredity

• It attempts to explain the the similarities and differences that occur among related individuals.

Genetics• Term coined in 1905 to describe a new emerging

field by William Bateson.

• From the Greek genētikos meaning origin, fertile, or productive.

• created to describe the elucidation of the phenomena of heredity and variation, the physiology of descent.

What are we going learn?

• Apply Mendelian Genetics and calculate the probabilities of transmission.

• The exceptions to Mendel’s laws


• What is a gene?

• How do we know where genes are located?

• How do genes break, and what is the consequence?


• How do we read the information that is found inside of a gene?

• How is this information regulated?


• How can a gene move within and individual?

• How can a gene variation move within a population?

Why do we care about Genetics?

Dinosaur Cloning Genetic PredeterminationGenetically-modified Super-humans

Why do we care about Genetics?PharmacogenomicsDiagnosis

Forensic Identification Gene Therapy

Why do we care about Genetics?Artificial Selection Ecological Research

Breeding

Modern GMO’s

Why do we care about Genetics?Public Policy

Lysenkoism

Eugenics Movement and genocide

GMO Labeling and Growth

“An exact determination of the laws of heredity will probably work more change in man’s outlook on the world, and his power over nature, than any other advance in natural knowledge that can be foreseen.” W. Bateson

Take Home Message

• No matter what you plan on doing, you are here because genetics has many practical, scientific, and societal applications.

Setting the Stage• Why do some of the

children look like only one of the parents, while some of the other children look more like the great, great grandparents?

• What causes the similarities and differences of appearance and the skipping of generations?

Figure 2.1

Inheritance Theories 400-350 B.C.

• Aristotle

• The semen was purified form of blood that was transferred to the female. In it was all that was required for the offspring. It mixed with menstrual blood, that nourished the offspring and helped it grow.

• Hippocrates

• Each part of the body created something that represented itself. These “somethings” collected in the male, and were transmitted to the female. This was a continuing process; therefore, it allowed for the transfer of acquired characteristics.

• Plato

• Followed Hippocrates Theory; however, disagreed that acquired characteristics could be inherited.

Inheritance Theories 1860’s

• Galton’s Law of Ancestral Inheritance

• Actually did transfusions to test Aristotle’s idea that the blood was critical for inheritance.

• Offspring received traits from their ancestors; however at a decreasing amount.

1/4

1/81/161/32


• Darwin’s Theory of Pangenesis

• Particles, called gemmules, were collected from all parts of body (exact miniatures), and became concentrated in germ cells

• Very similar to Hippocrates theory.

Hartsoecker in 1695


• Blending Inheritance

• Substances were blended together to yield unique individual with traits from both parents

X

The Hybridizers• Josef Kölreuter

• First Scientist to hybridize a plant (Tobacco) for research.

• Karl Friedrich von Gärtner

• Hybridized 700 species together to create 10,000 Hybrids.

• Knight (1823), Goss (1824), and Seton (1824)

• Worked with Pea Plants, and made many of the same crosses Mendel would do; however, they were not able to make useful predictions.

Gregor Johann Mendel• Came from a farming background

(rural Austria/Currently Czech Republic)

• Joined the Augustitian Monastery in Brno at 21.

• At 28, enrolled in the University of Vienna, after failing his teaching exam.

• Study Mathematics (Combination Theory), Physics (With Doppler), Paleontology, and Biology (Scientific botany).

Mendel’s Experiment• Goal: To deduce the law according

to which traits appear in successive generations.

• Model: Psium sativum - The Garden Pea

• Numerous Varities

• Short Generation time (3 Months)

• Easily identifiable Traits.

• Easy to cross

Mating Psium sativum

Vocabulary

Cross: The deliberate mating of 2 parental strains to obtain a desired offspring

How was Mendel’s Experiment Different?

• Different Philosophy

• Characters of the plant vs. Whole plant

• Application of precise counting, record keeping, and mathematics.

• Made predictive models that he could test.

Mendel’s Visible Traits

Vocabulary

Phenotype: The physical appearance of a trait

Mendel’s First Cross• Round Vs. Wrinkled

X

100% Round

Vocabulary• Round Vs. Wrinkled

X

100% Round

P1

F1

Vocabulary• Round Vs. Wrinkled

X

100% Round

P1

F1

Parental Generation

Filial Generation

Mendel’s First Cross• Round Vs. Wrinkled

X

100% Round

P1

F1

Mendel said that that the round trait is dominating the

wrinkled, or alternatively wrinkled

is recessive.

Mendel’s First Cross• Round Vs. WrinkledP1

F1

X

250 Plants

F2

Mendel’s First Cross• Round Vs. WrinkledP1

F1

X

250 Plants

F2 5474 round 1850 Wrinkled

2.96:1

Mendel’s Second Cross

3.01:1

Mendel’s Second Cross

3.01:1

XA a

Aa

A a

Mendel’s F1 Results

Mendel’s Results

Mendel’s Conclusions• Traits have two forms that can each breed true

• The trait that appears in F1 progeny is the dominant form

• The trait that is hidden in the F1 progeny is the recessive form

• Progeny inherit one (elemente) unit from the maternal parent and the other unit from the paternal parent. These units remain discrete, and can reappear in the second generation.

What happens in the F3?Aa

A aA

A A aa

100% Green100% Yellow 3:1 Yellow:Green

F1

F2

F3

Self

Self Self Self

1/3 2/3

Let’s Revise the modelAa

Aa aA

A A aa

100% Green100% Yellow1:2:1 Yellow:Yellow:Green

F1

F2

F3

Self

Self Self Self

Aa

Mendel Makes a Prediction

Aa X a

Testcross: A cross that mates the F1 to a recessive form.

Aa a1:1

Mendel’s Model Holds Up!

Aa X a

Aa a

2/3XA a

Aa

1/3

100% Yellow 50% Yellow 50% Green

Let’s Revise Mendel’s Model

Aa

aaAa

XAA aa

1:1:1:1

AA

Aa Aa AaX

Aa

Vocabulary

Aa

aaAa

XAA aa

1:1:1:1

AA

Aa Aa AaX

Aa

• Zygote: zugōtos (yolked), The cell created from the fusion of the egg and sperm/pollen.""

• Gametes: The specialized cells (egg and sperm/pollen) that transmit the heritable material from one generation to the next.

Vocabulary• Gene!• Coined by Wilhelm Johannsen in 1909, “Hypothesis

Free” to unify the language although derived from Pangens."

"• “many characteristics of the organism are specified in

the gametes by … determiners which are present in unique, and independent ways.”""

• A locatable region of genomic sequence, corresponding to a unit of inheritance, which is associated with regulatory regions, transcribed regions and/or other functional sequence regions.

Physiological Units Gemmules Pangens

Ideoblasts Plasomes Biophores

} Gene

Vocabulary

Aa

aaAa

XAA aa

1:1:1:1

AA

Aa Aa AaX

Aa

• Allele: Allelomorph - (allēlēn (of one another) and morphē (form), Alternate forms of the same gene.""

• homozygote: homos (same), Individuals with the same allele. ie. the purebreds - AA and aa.""

• heterozygote: hetro (different), Individuals with different alleles. ie. the hybrids - Aa ""

Vocabulary

Aa

aaAa

XAA aa

1:1:1:1

AA

Aa Aa AaX

Aa

""

• Phenotype - The physical appearance of the trait.""

• Genotype - The alleles that are present.""

• Dominant: The phenotype that is observed in the F1 progeny when 2 true breeding strains are crossed.""

• Recessive: The phenotype that is masked in the F1 progeny when 2 true breeding strains are crossed.""

""

Reginald Punnett

Aa

aaAa

XAA aa

1:1:1:1

AA

Aa Aa AaX

Aa

Aa

A

AA aa

a

Aa

Eggs

a A

Aa AA

aa aA

A

a

Pol

len

Gra

ins

×

×

Female Male Hermaphrodite

Mendel’s Dihybrid CrossWhat if we look at two genes at once?

Y (yellow) dominant to

y (green)

R (round) dominant to r (wrinkled)

Pea color Pea texture

Mendel’s Dihybrid CrossFirst, cross a purebred plant that produces round, yellow peas to a purebred plant that produces wrinkled, green peas.

RRYY x rryyP

RrYyF1

Mendel’s Dihybrid CrossThe F1 plants produce 4 different combinations of alleles, one allele for each gene.

"

"

"

"

What do you expect in the F2 generation?

RrYy

RY Ry rY ry

Mendel’s Dihybrid Cross

RY Ry rY ry

RY RRYY RRYy RrYY RrYy

Ry RRYy RRyy RrYy Rryy

rY RrYY RrYy rrYY rrYy

ry RrYy Rryy rrYy rryy

RrYy

RrYy

Mendel’s Dihybrid CrossRY Ry rY ry






R–Y– 9/16

R–yy 3/16

rrY– 3/16

rryy 1/16

There we predict that Mendel found:


R–Y– 9/16

R–yy 3/16

rrY– 3/16

rryy 1/16

There we predict that Mendel found:

315

108

101

32

9.8

3.5

3.2

1

What Mendel Found.

Take Home Message

• There are multiple forms of a gene, known as alleles.

• Alleles segregate between the gametes so that each offspring received one from each parent.

• The relationships of these traits can be assessed by crosses (monohybrid, dihybrid, and test cross).

Mendel Publishes!• Presented to the local scientific society on his

results, and published it in their journal (1865).

• Ordered 40 reprints, and sent them to some of the top scientist that he knew, and only heard back from one, Nageli.

• Nageli was really only interested in Hawkseed, so Mendel volunteered to work with Nageli to determine if the ratios were relevant to other organisms.

Mendel• Hawkseed is has really small flowers that required

Mendel to work under the microscope, and due to poor optics, he almost lost his sight.

• Unfortunately, Hawkseed reproduces via apomixis (the cloning of the mother cell). This meant that Mendel could not replicate his ratios.

• He was also elected head abbot of the monastery, and as such had a larger administrative role. Specifically, he spent most of his time finding taxes that were being levied against the monastery.

The soap opera of rediscovery.

• 1899 DeVries

• Looks a Lychinis leaves, Finds 99 hairy:54 Smooth. Stated that this approached a 3:1 ratio; however no mention of Mendel until the German translation comes out several months later.

• 1900 Correns

• DeVries arch rival wrote a letter to the editor pointing out that DeVries’ number don’t really add up, and that he changed his language to match Mendel’s even though he barely cited his work.

• Defines Mendel’s laws, and identified several exceptions.

• 1900 Von Tschermak

• Cited Mendel in his graduate thesis. Fought to be called a rediscover as he looked at this as his big break.

Mendel’s Law of Segregation

• “In the formation of these cells, all elements participate in an entirely free and equal arrangement, by which it is only the differentiating ones which mutually separate themselves.”

• There are 2 alleles per parent, and each offspring gets one allele from each parent.

Mendel’s Law of Independent Assortment

• “...It is demonstrated at the same time that the relation of each pair of different characters in hybrid union is independent of the other differences in the two original parental stocks.”

• The segregation of one pair of alleles is not effected by the segregation of a second pair of alleles.

We need a better way.What about trihybrid crosses? Tetrahybrid?

Simple Statistics for Genetics

Probability = # times event is expected to happen # opportunities (trials)


• The Product Rule

• If events A and B are independent, the probability that they occur together, P(A and B), is P(A) X P(B)


• The Sum Rule

• Used when two outcomes are mutually exclusive - ie. if one outcome prevents the other.

• To calculate the chance of two mutually exclusive outcomes that both satisfy the desired conditions, add their respective probabilities together.

• P(A OR B) = P(A) + P(B)

Monohybrid Cross Example

• What is the probability that the offspring will be Heterozygous (Yy)?

• Remember that are 2 ways to be heterozygous Yy or yY.

YY Yy

Yy yy

Y y

Y

y

Monohybrid Cross Example"

• P(Yy)= the probability of getting the Y from the female, and y from the male.

• P(yY)= the probability of getting the y from the female and Y from the male.

YY Yy

Yy yy

Y y

Y

y

These are independent, so we use the product rule.

• P(Yy)= P Y(1/2) X P y(1/2)


YY Yy

Yy yy

Y y

Y

y

• P(Yy)= P Y(1/2) X P y(1/2)

• P(Yy)= P Y(1/2) X P y(1/2)


YY yY

Yy yy

Y y

Y

y

• P(Yy)= P Y(1/2) X P y(1/2)

P(Yy)=1/4

P(yY)=1/4

• P(Yy)= P Y(1/2) X P y(1/2)


YY yY

Yy yy

Y y

Y

y

• P(Yy)= P Y(1/2) X P y(1/2)

P(Yy)=1/4

P(yY)=1/4

• What is the Chance that the offspring will be Heterozygous (Yy)?

• Since we want to know if it is Yy or yY we want to use the Sum Rule


YY yY

Yy yy

Y y

Y

y

P(Yy)=1/4P(yY)=1/4

P(Yy or yY)= P(Yy)+P(yY)P(Yy or yY)=(1/4)+(1/4)

P(Yy or yY)= 1/2

A Little Harder

• In a dihybrid cross, between Round and Yellow F1 peas (RrYy), what proportion of the F2 would be Round and Green?

A Little Harder• In a dihybrid cross, between Round and Yellow F1

peas (RrYy), what proportion of the F2 would be Round and Green?

Two possible genotypes: RRyy or Rryy




• P(yy)= P y(1/2) X P y(1/2)

P(yy)=1/4

• P(RR)= P R(1/2) X P R(1/2)

P(RR)=1/4 P(RRyy)=P(RR) X P(yy)P(RRyy)=1/4 X 1/4

P(RRyy)=1/16


peas (RrYy), what proportion of the F2 would be Round and Green?Two possible genotypes: RRyy or Rryy (or rRyy)


peas (RrYy), what proportion of the F2 would be Round and Green?Two possible genotypes: RRyy or Rryy (or rRyy)

• P(yy)= P y(1/2) X P y(1/2)P(yy)=1/4

• P(Rr)= P R(1/2) X P r(1/2)P(Rr)=1/4

P(Rryy)=P(Rr) X P(yy)P(Rryy)=1/2 X 1/4

P(Rryy)=1/8

• P(rR)= P r(1/2) X P R(1/2)P(rR)=1/4

P(Rr or rR)=p(Rr) + p(rR) P(Rr or rR) = 1/2




P(RRyy)=1/16 P(Rryy)=1/8=2/16

P(RRyy or Rryy)= P(RRyy)+P(RrYy)

P(RRyy or Rryy)= 1/16 + 2/16

P(RRyy or Rryy)= 3/16

Mendel’s Dihybrid CrossRY Ry rY ry





P(RRyy or Rryy)= 3/16

• What is the probability of not being Yellow and Round?

• What is the probability of not being Yellow and Round?

P(Green,Round; Yellow, Wrinkled; or Green, Wrinkled)

Or

P(1-Yellow,Round)

• What is the probability of not being Yellow and Round?P(1-Yellow,Round)

What Genotypes are the genotypes that produce Yellow Round Phenotypes?


What Genotypes are the genotypes that produce Yellow Round Phenotypes?

YYRR YyRR YYRr YyRr


P(Rr or rR)=p(Rr) + p(rR)

P(1-[YYRR or YyRR or YYRr or YyRr])



P(Yy or yY)=p(Yy) + p(yY)




P(Yy or yY)=p(Yy) + p(yY) P(Yy or yY) = 1/2


P(RR)= P R(1/2) X P R(1/2)





P(RR)= P R(1/2) X P R(1/2)P(RR)=1/4

P(YY)= P Y(1/2) X P Y(1/2)





P(RR)= P R(1/2) X P R(1/2)P(RR)=1/4

P(YY)= P Y(1/2) X P Y(1/2)P(YY)=1/4

P(YYRR)= 1/4 X 1/4 = 1/16

P(YyRR)= 1/2 X 1/4 = 1/8

P(YYRr)= 1/4 X 1/2 = 1/8

P(YyRr)= 1/2 X 1/2 = 1/4

• What is the probability of not being Yellow and Round?P(1-Yellow,Round)P(1-[YYRR or YyRR or YYRr or YyRr])P(YYRR)= 1/4 X 1/4 = 1/16

P(YyRR)= 1/2 X 1/4 = 1/8

P(YYRr)= 1/4 X 1/2 = 1/8

P(YyRr)= 1/2 X 1/2 = 1/4

P(1-[1/16 + 1/8 + 1/8 + 1/4])

P(1-[9/16])

• What is the probability of not being Yellow and Round?P(1-Yellow,Round)P(1-[YYRR or YyRR or YYRr or YyRr])P(YYRR)= 1/4 X 1/4 = 1/16

P(YyRR)= 1/2 X 1/4 = 1/8

P(YYRr)= 1/4 X 1/2 = 1/8

P(YyRr)= 1/2 X 1/2 = 1/4

P(1-[1/16 + 1/8 + 1/8 + 1/4])

P(1-[9/16])The probability of not being Yellow and Round is: 7/16

The Probability of NOT.

The probability of not being Yellow and

Round is: 7/16

RY Ry rY ry





A tetrahybrid crossYou allow an F1 plant heterozygous for 4 traits self cross. What proportion of the peas will be AAbbCcDd?

lecture 1

Documents

genetics term

mendelian genetics

interactive genetics

science of heredity

genetics instructor

pts exam

gene variation

pts discussion