Chapter 9: Part 2 E X A M 4

• The next question Mendel asked, was “What happens when I study the inheritance of TWO different traits at the same time?”

• Dihybrid crosses • Human Traits and diseases controlled by a single gene • Pedigrees • “Beyond Mendel” – Incomplete dominance – Multiple alleles – Pleiotropy and Polygenic inheritance – Linked genes – Sex linked genes and sex-linked disorders

Breeding plants identical for 5 traits, but differing in 2 Dominant Flower color

Purple

Flower position Axial

2. Seed color

Yellow

Dominant

Recessive

Round

There are two different hypotheses for gene assortment in a dihybrid cross

Recessive

Pod shape

Inflated

Constricted

Pod Color

Green

Yellow

White

1. Dependent assortment 2. Independent assortment

Terminal

Green

Stem length

1. Seed shape

To answer this question, he used Dihybrid Crosses • Cross two true breeding plants differing in two characters

Tall

2. Seed color

Yellow

Green

1. Seed shape

Round

Wrinkled

Dwarf

Wrinkled

One plant has the genotype RRYY, one plant has the genotype rryy. What is the phenotype of each plant?

Dihybrid Cross • P generation: RRYY x rryy (true breeding) • F1 generation: all offspring are heterozygous for both characters Rr Yy

• Question? Are Y and R sorted into gametes together as a package, or separately?

The question, then, is directed at the gametes of the F1 generation.

• Will Y and R stay together generation after generation (is their assortment dependent) OR are they inherited independently of one another?

What type of gametes will the F1 generation have? Will the gametes have a combination of parental traits, or will the gametes produced look like the gamete it received from parents?

1

What happens in a dihybrid cross -If it is dependent assortment?

If it is dependent assortment?

P generation

F1 generation

First, if it is dependent assortment, what are the possible gametes of the F1 generation?

RY What would the outcome look like if it is dependent assortment?

ry

Gametes are identical to those received.

The genes are passed on as a ‘package’ exactly as they were inherited.

If it is independent assortment?

If it is independent assortment?

• What are the possible gametes that the F1 generation can make? (meiosis)

• What are the possible gametes that the F1 generation can make? (meiosis) R

R

r OR

R

y

y

RY

ry

Ry

Y

y

Ry

rY

r

RY

Y

r

yr

Y

rY

2

Dependent Assortment

RY

Independent Assortment

RY

ry

Ry

RY

yr

ry

RY ry

rY

Which of the two predicted outcomes did Mendel see? Which hypothesis, or prediction did his data resemble?

Mendel’s 2nd Law • The law of independent assortment • States that each PAIR of alleles segregates independently of the other pairs during gamete formation • Supported by the 9:3:3:1 phenotypic ratio he observed during the dihybrid cross His data (the seeds of the pea plants) looked like this.

Mendel’s 2nd Law Different alleles can line up on either side of the metaphse plate, independent of other gene pairs

OR

Need a reminder of Mendel’s first law? • The 2 alleles separate (segregate) during gamete formation • Meaning, egg or sperm get only one of 2 alleles

Baby

****Mendel’s law of segregation****

3

Mendel’s Contributions 1. Segregation (the two alleles of each gene an organism has are separated during gamete formation) 2. Independent Assortment: as far as Mendel found, which gamete (sperm or egg) an allele for one gene ends up distributed to is independent of other genes

• Figuring out the possible gametes for a dihybrid cross, knowing that genes sort independently

Distribute!! FOIL

• YyRr (Yy) (Rr)

=YR, Yr, yR, yr

Easy Practice problem • Calculating probabilities, looking at one gene (R), with two alleles (R or r)

• In pea plants, round seeds R is dominant to wrinkled seeds r. In a genetic cross of two plants that are heterozygous for this trait, what fraction of the offspring should have round seeds? A. none B. 1/4 C. 1/2 D. 3/4 E. All

Easy Practice problem • In pea plants, round seeds R is dominant to wrinkled seeds r. In a genetic cross of two plants that are heterozygous for this trait, what fraction of the offspring should have round seeds?

Practice problem • In a dihybrid cross, BbCc x BbCc, what fraction of the offspring will be homozygous for both recessive traits?

A. 1/16 B. 1/8 C. 3/16 D. 1/4 E. 3/4

A. none B. 1/4 C. 1/2 D. 3/4 E. All

What fraction of offspring are heterozygous?

4

Some human traits (not many) exhibit simple Mendelian Inheritance What does that title mean??

• How did geneticists arrive at this conclusion? • Do you think they used test crosses on humans??

Some human traits exhibit simple Mendelian Inheritance Dominant

Recessive “Simple Mendelian Genetics” refers to ONE TRAIT being controlled by ONE GENE, and that the GENE has only two possible alleles, and that one allele is completely dominant over the other, recessive allele.

Some human disorders are controlled by a single gene

Family Pedigrees

What is a carrier? Who in this pedigree is a carrier for this deafness gene?

Recessively Inherited Disorders that exhibit simple Mendelian Inheritance •Some genetic disorders are known to be inherited as simple recessive traits. (For the recessive phenotype to be seen, the organism needs TWO copies of the recessive allele). •Albinism, Tay-Sachs, cystic fibrosis

• Remember that genes code for proteins! • Carriers = genotype is heterozygous but phenotype is normal

C

C

CC

c

Cc carrier

c

Cc carrier

cc Cystic fibrosis

Recessively Inherited Disorders • Cystic Fibrosis (CFTR) • Sickle cell anemia (hemoglobin) • How do heterozygotes fair? • With some diseases the heterozygotes are perfectly healthy, while with other diseases the heterozygotes have an intermediate phenotype • Why don’t these recessive alleles become ‘weeded out’ of the gene pool? • Is it obvious, or outwardly apparent, if someone is a carrier for a recessively inherited disorder? Why/why not?

5

Dominantly Inherited Disorders that exhibit simple Mendelian Inheritance

Dominantly Inherited Disorders

• These diseases require only ONE copy of allele to produce disease • How do carriers or heterozygotes fair? • (think about the Pp flowers) • Dominant alleles that cause a lethal disease are much less common than recessive alleles that do so • Often arise from spontaneous mutations in sperm or egg

• Achondroplasia (form of dwarfism) – Heterozygotes have dwarf phenotype – Homozygous dominant embryos spontaneously abort

• 99.9% of population are NOT achondroplasic and are homozygous recessive

YEOWCH!

“Beyond Mendel”

Dominantly Inherited Disorders

• Mendel laid down important rules that established the foundations of genetics • But, his two principles do not explain everything • Next, we’ll look at examples of inheritance that do not adhere to Mendel’s rules.

• Huntington’s Disease is a dominantly inherited disorder • Why don’t these dominant alleles become ‘weeded out’ of the gene pool? • What is the average age of onset of Huntington’s disease?

Glitch #1 (Mendel was lucky)

Glitch #1 (Mendel was lucky)

P Generation

•Incomplete dominance

Red RR

White rr

Gametes

• Heterozygotes have a unique appearance between the phenotypes of the homozygous recessive or dominant parents

F1 Generation

Pink Rr

Gametes

1/ 2

Why is this not blended inheritance? How do we know?

1/ 2

1/ 2

Eggs

F2 Generation

• Incomplete dominance (another example)

r

R

R

1/ 2

R

r

Red RR

r

1/ 2

Sperm

R 1/ 2

r

Pink rR

Pink Rr White rr

6

LDL Receptor

Glitch #2 (Mendel was lucky) • Another exception: Multiple Alleles • ABO blood groups • Blood groups are determined by the type of glycoproteins that are attached to the surface of red blood cells • An enzyme (protein) is responsible for ‘attaching’ these glycoproteins to the surface…this is the protein in question ‘A’ glycoprotein RBC

Mulitple Alleles ABO Blood Groups Three alleles:

IA:

Enzyme that attaches A to RBC surface

IB

Enzyme that attaches B to RBC surface

i Enzyme that attaches neither A or B to RBC surface IA and IB are dominant over i. A and B are co-dominant

ABO Blood Groups

Antibodies that would be in the blood, FOLLOWING, exposure to blood from a donor of a different blood type or, put another way, the antibodies a person with that blood type is capable of making upon ‘seeing’ foreign blood

4 phenotypes, 6 genotypes

Thus, O is the “universal donor” and AB is the “universal acceptor”

7

Another blood type question

Practice Question: Who’s your daddy? • Suppose mother is Type A, baby is Type B. • Consider these three putative fathers; can any be the actual father? #1 (Type A): Yes or no? #2 (Type B): Yes or no? #3 (Type O): Yes or no? What does the PHENOTYPE of DAD have to be? What are the possible genotypes of DAD?

Which of the following matings cannot produce a child with blood type O? The letters refer to blood types (phenotypes). a) b) c) d) e)

AxA AxB O x AB OxO none of the above

Hint: for each possible multiple choice answer, write out what the GENOTYPES of the two parents COULD be!! For instance, a phenotype of A could have a genotype of:

IAIA or IAi

Glitch #3: Pleiotropy • Most genes have multiple phenotypic effects (not only one).

Pleiotropy One gene

multiple effects One gene

multiple effects

Glitch #4: Polygenic Inheritance • Mendel studied traits that were ‘either or’ • Many characters vary in a population along a continuum • Polygenic inheritance = 2 or more genes affect a single phenotypic character Consequence of

• Skin color/ Height

One trait

• Polygenic Inheritance of a trait results in a broad range of phenotypes

multiple genes

8

Even further departure from Mendel: Effect of the Environment on Phenotype

Chromosomal Basis of Inheritance In 1902 the Chromosome Theory of Inheritance was proposed. In states that Mendelian genes have specific loci on chromosomes, and these chromosomes undergo segregation and independent assortment.

• Many factors, including genetics and environment determine the phenotype

• Effects of Nutrition on height • Effects of Exercise on build • Effects of elevation on RBC count (but not blood type, right?)

Oh! They finally realized that those gene-things were ON the chromosomes! A gene resides on a chromosome…TA-DA!!!!!

Mendel got lucky here, again, why? • In Mendel’s experiments, he found that the inheritance of two different characters was independent.

Correlating the results of Mendel’s dihybrid crosses with the behavior of chromosomes during meiosis

Mendel got lucky here, again, why? • In Mendel’s experiment, although he didn’t know it at the time, the genes he studied during the dihybrid cross were on DIFFERENT chromosomes!

R

Linked Genes • The number of genes in a cell is much, much greater than the number of chromosomes.

r

Human chromosome number 1 contains ~2400 genes!!

Y

y

Hmm, in the microscope I see that the nuclei of pea plants have 14 chromosomes, and there are two of each size. There have to be more than 14 genes in a pea plant, right?

9

Lets look at a different dihybrid cross

Linked Genes • Genes located on the same chromosome that tend to be inherited together

In this cross (for some reason) Purple is still dominant, but to red. Long pollen is dominant to round pollen. P generation (grandparents) are PPLL and ppll. What is the genotype and phenotype of all of the offspring?

a

A B

b

P generation

Short pollen

e

E

When the F1 plants self fertilize, notice the predicted and observed phenotypic ratios

F1 generation

Beyond Mendel

What Mendel had been observing…

A

P

a

p

We might expect to see the classic 9:3:3:1 ratio, as this is a diyhybrid cross!

Linked Genes

Linked Genes

• Genes located on the same chromosome that tend to be inherited together A

A P

a

a p

• Genes located on the same chromosome that tend to be inherited together • What does this mean, tend? Imply?

Vs.

A P P

a p

p

10

Linked Genes

Crossing Over

• Genes located on the same chromosome that tend to be inherited together • What does this mean, tend? Imply? CROSSING OVER

Get a room!!

How does linkage affect inheritance of two different characters? • If 2 genes are physically close together, on a chromosome arm, do you think they will be more or less likely to be separated during crossing over?

• Remember that in crossing over, homologous regions of chromosome ‘arms’ can swap information. • The point at which the arms cross is called the chiasma. • Everything beyond the crossing over spot, will be swaped

A

A

C

C

B

B

Recombination Frequency • Crossing over is random • Thus the more places/points for crossing over to physically occur, the greater the likelihood that two genes (A and B) will be separated or recombined, thus, the higher the recombination frequency.

A C B

What about B and C??

Constructing a genetic map Recombination frequencies reflect the distances between genes on chromosomes.

Thomas Morgan Hunt Utilized Drosophila melanogaster (fruit flies) to study genetics.

One map unit (or centrimorgan) = 1 % recombination frequency

11

Drosophila melanogaster as a model system • Single mating produces 100+ offspring • A new generation can be bred every two weeks • Only four pairs of chromosomes- 3 pairs of autosomes, 1 pair sex chromosomes (XX and XY)

•Unlike Mendel, Morgan does not have access to truebreeding strains. •He breeds flies for a year, looking for distinct varieties. •He discovers a male fly with white eyes, instead of red.

Look, important vocab over here!

Look at Me, I’m WILD!

In Drosophila, red eyes = Wild type (the most common phenotype in a natural population) white eyes = a mutant Phenotype (the less common version).

Those white eyes are so unusual

Morgan’s First Experiment: Morgan crosses a red-eyed female with a white-eyed male. ALL the offspring have red eyes. How would Mendel explain these results?? What would Mendel do next??

I like my mates WILDTYPE!

Mendel might say that Red eyes are DOMINANT to WHITE eyes, and the genotype of the mom in P generation was probably (homozygous dominant or heterozygous)????

Morgan’s Next Experiment: Morgan crosses two of the red-eyed F1 flies with each other. If all of F1 are heterozygous for eye color……..

What should he see if Mendel is correct??

Results: He DOES find a 3:1 ratio, but ALL of the white-eyed flies are male!! How ODD!

12

Morgan Discovers Sex-Linked Genes! (and wins Nobel Prize, 1933) He DOES find a 3:1 ratio, but ALL the white-eyed flies are male!! Was Mendel wrong?? What happened?!? This is weird.

Inheritance of a Sex-linked trait

Sex Chromosomes and Sex determination • In humans, and many other organisms, sex is determined by the presence of X and Y chromosomes.

X and Y chromosomes • Because the X chromosome is so much larger than the Y (carries more genes), the majority of sex-linked genes, not related to sex determination, are found on the X chromosome • If a gene resides on Chromosome X, how many copies does a female get? A male?

Human Sex-linked Disorders • Red-Green color blindness (enzymes that make pigments that absorb red or green wavelengths of light) • Duchenne muscular dystrophy (dystrophin) • Hemophilia (clotting factor) These are recessive traits!! It takes two copies of the recessive allele to present with the disorder (if you are female). HOW many copies does a male get?

13

Human Sex-linked Disorders If a male hemophiliac mates with a ‘normal’ woman, who happens to be a carrier for the mutated gene…

Xh

The Transmission of SEX-LINKED RECESSIVE Traits

Y

XH

Xh

What percent of their offspring are hemophiliacs? What percent are carriers?

Practice Question: Sex-Linked Chromosomal Inheritance If you see the number 7, then you do not have red-green color blindness. A totally color-blind person will not be able to see the number 7.

In this diagram “A” represents a dominant allele carried on the X chromosome; “a” represents the recessive allele. White boxes indicate unaffected individuals, light-colored boxes are carriers, and dark-colored boxes are affected individuals. Note that both males and females are affected by sex-linked disorders!

Practice Question If a color blind man has children with a heterozygous, “wildtype” woman, what are the chances that a daughter of theirs will be colorblind? What are the chances that their son will be colorblind? Can females be colorblind? What would the genotype of the parents have to be?

• How can the Y chromosome measure time? • How can mitochondrial DNA measure time?

• The Y chromosome is passed from father to son, more or less unchanged – There is very little space on the Y chromosome that isn’t critical to male development, mutations are rare – What about crossing over? – Is Y highly homologous to the X chromosome?

14

Y-chromosome Loci Analyzed by Family Tree DNA

• When rare mutations in the Y chromosome occur, they can be traced.

• Let’s say that the Y chromosome gets 1 new mutation/generation (much higher than the actual rate). If this is the case, then if two people have 10 differences between them, then they are 10 generations apart.

INDIVIDUALS

• Scientists use DNA, and changes in DNA sequence to estimate when things have happened in the past by assuming a certain rate of mutations over time.

Different Loci on the Y chromosome

Locus Sample

393

390

19

385a

385b

426

388

388

Mutations Relative to #2

#1

13

25

15

11

11

11

12

30

1

#2

13

24

15

11

11

11

12

30

0

#3

14

24

15

11

11

11

12

30

1

#4

13

24

14

11

11

14

12

28

4 or 5

How might you ‘plot’ this data on a tree? Where are the branches, or branch points? What do these points mean?

• Mitochondrial DNA is passed from mother to all offspring, essentially unchanged • Female offspring will then pass this DNA to their offspring……

Egg Mutations in mitochondrial DNA can be studied and traced back through time

Evolutionary Relationships Based on Amino Acid Sequences of a Protein

15