today is monday, december 8 th, 2014 pre-class: who’s your daddy, genetics? tell your neighbor...

Today is Monday,December 8th, 2014

Pre-Class:Who’s your daddy, genetics?

Tell your neighbor something about him.

In This Lesson:Mendelian

Genetics and Heredity

(Lesson 3 of 3)

Today’s Agenda

• Mendelian genetics– The Return of the Punnett Square!

• Inheritance and heredity– Complete dominance, incomplete dominance…

• Pedigrees• Chromosomal mutations• A geep, a zorse, a beefalo, and a cama.

• Where is this in my book?– Chapters 14-15.

• I will be skipping around between the two, but it’s all in there.– And by “all” I mean “mostly.”

» You’ll be fine.

By the end of this lesson…

• You should be able to recognize patterns of inheritance.

• You should be able to determine the probability of certain genotypes and phenotypes occurring from a given cross.

• You should be able to read a pedigree.• You should be able to identify several

chromosome-level mutations.

Introduction

• Bill Bryson – Genetic Relations

Warm-Up

• Genetics Practice 1: Basic Mendelian Genetics worksheet– The last one may be a little new…we’ll talk about it.

The Big Disclaimer

• No one in this class will be able to 100% determine their genetic lineage.

• It’s like a putting on a play – the script may be the same each time, but exactly how it looks on stage might be different.

• I’ll explain what I mean by this with a story.

Gregor Mendel

• As you might guess, the story starts with Gregor Mendel, the Austrian monk.– By the way, he had a formal

scientific training and a library. He wasn’t scientifically illiterate like sometimes he’s portrayed.

• That said, modern genetics began in the garden of a monastery sometime in the mid-1800s.

Gregor Mendel’s Pee Pea

• In an excellent example of the scientific method in action, Mendel noticed seven traits that only existed in one of two different possibilities:– Flowers are purple or white, located at the end of the stem

or lower down.– Stems are long or short.– Seeds are green or yellow, round or wrinkled.– Peapods are green or yellow, inflated or condensed.

• Through controlled experiments with large sample size (plus a fair degree of luck and patience), Mendel began to pick up on the notion of dominant/recessive traits.

Pea Plant?

Mendel’s Luck

• Had Mendel attempted to study humans, he wouldn’t have had much success. Unlike us:– Peas can self-fertilize OR cross pollinate.– Their generation time is short.– Easily-observed traits follow simple inheritance.

• Remember “detached/attached earlobes,” “tongue rolling,” and “hitchhiker’s thumb” from previous classes?– Most evidence suggests those are probably not as

simple as “dominant” or “recessive.”

Mendel + Darwin =

• Darwin, working around the same time, set forth the idea of “descent with modification.”– He had the “why” of modification but not the “how.”

• Mendel, whose work was published in 1866 but not actually recognized until 1900, provided the “how.”

• Thus, Darwin and Mendel are the “parents” of biology.– Without their work, nothing makes sense.

About “Heritable” and “Progeny”

• Just for the record, the word “heritable” means “can be passed down.”

• If something is not heritable, it means there likely isn’t a genetic component to it.

• Also, you’ll [uncommonly] see the word “progeny.”– It means the same thing as offspring.

• Okay then, back to our PowerPoint…we have a lot of slides to go.

True Breeding

• Mendel started his experiments with true breeding plants as his parental generation.– True breeding plants are those that lead to offspring of their

own phenotypes.• In this case, Mendel cross-pollinated an all-white population with an

all-purple population.

– This is the P Generation.• The offspring of the P generation was entirely purple.– This is the F1 generation (first filial generation).

• Mendel let the F1 generation self-pollinate, creating the F2 generation.– And thus the drama begins.

Mendel’s Generations

• The P generation is all white and all purple.– They’re cross-pollinated.

• The resulting F1 generation is all purple.– They’re allowed to self-pollinate.

• The resulting F2 generation is purple and white (!?!?) in a 3:1 ratio.– How did white reappear?


• As Mendel (and you) learned, the disappearance of white flowers suggested that purple flowers are somehow dominant to white flowers.

• The reappearance of white flowers suggested that something about the white flowers was carried by those F1 purple flowers.

• Out of further studies and many more years arose Mendel’s laws.– You know these, although perhaps not by name.

Mendel’s Laws

1. Law of Segregation– During meiosis, alleles

segregate into separate gametes.

– Thus, each allele for a trait is passed on separately.

• This process occurs in metaphase I, though Mendel wasn’t aware of that.

GGG

G

ggg

g

GgG

g

Mendel’s Laws

2. Law of Independent Assortment– The segregation process of

metaphase I is random.• Remember that?

– NOTE that there are exceptions to this rule that we will discuss later.

GGG

G

ggg

g

GgG

g

Mendel’s Laws

3. Law of Dominance– Some alleles/traits are

dominant to others.• Remember that?

GG

gg

Gg

What Do Mendel’s Findings Tell Us?

• Traits, coded for by genes, come in different versions.– An allele is thus a version of a

gene.• We all have a gene for hair color,

but we have different alleles.

– Alleles vary in the sequence of nucleotides at the gene’s locus.• A locus is the spot on a

chromosome/DNA molecule where a gene is located.

• Plural = loci.

What Do Mendel’s Findings Tell Us?

• Some traits mask others.– Discrete inheritance, not blended.– The recessive allele may make a

malfunctioning protein or not function at all.

• Out of this arises the concept of a genotype and phenotype:– Genotype = underlying alleles.– Phenotype = outward appearance.

GgG

g

Test Cross

• As we learned way back when we did Hardy-Weinberg, we can’t know the underlying genotype of an individual exhibiting a dominant phenotype.– If B is dominant for “brown hair,” someone with brown

hair can be Bb or BB.• To figure out the genotype, a test cross can be

performed.– Cross the unknown dominant with a [known] recessive.

Test Cross

http://www.mhhe.com/biosci/genbio/enger/student/olc/art_quizzes/genbiomedia/0193.jpg

Monohybrid and Dihybrid Crosses

• The test cross from the previous slide’s example was a monohybrid cross.– Only one trait analyzed.

• As you recall, there are also dihybrid crosses.– Two traits analyzed.

• These can be a time-consuming pain to solve if you don’t know some tricks, so let’s do a little review, starting with the full process.

Solving Dihybrid Crosses

1. Identify the parent genotypes.– DdHh and DdHh, for example.

• Let’s make D = dark flowers and d = light flowers.• H = hard fruit, h = soft fruit.

2. FOIL the genotypes.– First, Outer, Inner, Last– DH, Dh, dH, dh– DH, Dh, dH, dh

3. Place one FOIL result across the top, the other down the side of a 4x4 square.

4. Solve as normal.

FOILing

• How to FOIL:– [First, Outer, Inner, Last]

DdHhDdHh

FirstOuterInnerLast

DH

Possible Allele Combinations

DhdHdh

DH Dh dH dh

DH DDHH DDHh DdHH DdHh

Dh DDHh DDhh DdHh Ddhh

dH DdHH DdHh ddHH ddHh

dh DdHh Ddhh ddHh ddhh

DdHh x DdHh

Which plants will have the dominant phenotype for both traits?Which plants will have the dominant phenotype for flowers but recessive for fruit?Which plants will have the dominant phenotype for fruit but recessive for flowers?Which plants will have the recessive phenotype for both traits?

9:3:3:1

Now for the shortcuts…

• If both parents are completely heterozygous…– (like we just did – DdHh x DdHh)

• …the ending phenotypic ratio is 9:3:3:1.• 9/16 showing both dominant phenotypes.• 3/16 showing a dominant/recessive phenotype.• 3/16 showing a recessive/dominant phenotype.• 1/16 showing both recessive phenotypes.

Shortcut: Rule of Multiplication

• What if it’s not so easy?• Imagine Ddhh x DdHh. You could do that with

a dihybrid cross, but you don’t have to.• Thanks to the laws of probability, we can avoid

the giant Punnett square.– This one’s going to require a little more

explanation.

Shortcut: Rule of Multiplication

• From a [fair] coin flip, what is the chance of getting heads?• 50%, or 0.5.

• From two coin flips, what is the chance of getting two heads?• 25%, or 0.25. (0.5 * 0.5)

• So you can take the probability of the first event and multiply it by the probability of the second event.– Key: Do this when you need the probability of BOTH things

happening together, not happening separately.• If I asked for the probability of getting heads on one of the two

flips, you’d do something different.

Shortcut: Rule of MultiplicationGenetics Example

• In our previous dihybrid cross (DdHh x DdHh), what is the probability of offspring with dark flowers and hard fruit?– We know it’s 9/16, but let’s figure it out another way.

• Cross each trait individually as a monohybrid.

• Multiply 0.75 * 0.75 = 0.5625, or 56.25%.• And what is 9/16? 0.5625!

• Key: Think of this rule like “AND” – what are the chances of “A” AND “B” happening?

D dD DD Ddd Dd dd

H hH HH Hhh Hh hh

75% chance of D75% chance of H

Rule of Multiplication: You Practice• This one’s popular:• In a cross between AaBbCc and AaBBCC, what is the

probability of getting AaBbCC as offspring?– Probability of Aa is 0.5.– Probability of Bb is 0.5.– Probability of CC is 0.5.

– So, 0.5 * 0.5 * 0.5 = 0.125, or 12.5%, or 1 in 8.

A aA AA Aaa Aa aa

B BB BB BBb Bb Bb

C CC CC CCc Cc Cc

Shortcut: Rule of Addition

• Suppose, however, that you just want to know the likelihood of two unrelated things happening.

• Imagine you’re drawing from a deck of playing cards and want to know the likelihood of getting a King or a Queen. There are 52 cards in the deck with 4 Kings and 4 Queens.– Add the probabilities together!– 4/52 + 4/52 = 8/52, or 4/26, or 2/13.

• Key: Think of this rule like “OR” – what are the chances of “A” OR “B” happening?

Shortcut: Rule of AdditionGenetics Example

• In a cross Pp x Pp, what is the likelihood of the offspring being heterozygous?– You know it will be 50% from the usual Punnett Square.

• The first parent would donate a P (0.5 chance) and the second would donate a p (0.5 chance) OR

• The first parent would donate a p (0.5 chance) and the second would donate a P (0.5 chance).

• So the likelihood of the first event happening is 0.5 * 0.5 or 0.25.

• The likelihood of the second event happening is 0.25 also.– Since both ways “work,” add them together: 0.25 + 0.25 = 0.5, or

50%.

Rule of Addition: You Practice

• In a cross between AaBbCc and AaBBCC, what is the probability of getting AABbCc or AABBCC as offspring?– For AABbCc:

• Probability of AA is 0.25.• Probability of Bb is 0.5.• Probability of Cc is 0.5.• TOGETHER: 0.25 * 0.5 * 0.5 = 0.0625.

– For AABBCC:• Probability of AA is 0.25.• Probability of BB is 0.5.• Probability of CC is 0.5.• TOGETHER: 0.25 * 0.5 * 0.5 = 0.0625.

– Combined: 0.0625 + 0.0625 = 0.1250 or 1/8.

Probability Rules:Final Problem

• From parents AaBBCcddEeFF and AAbbCcDdeeFf, what is the likelihood of getting AABbCCddeeFF?• Aa x AA = 50% likelihood of AA (.5).• BB x bb = 100% likelihood of Bb (1).• Cc x Cc = 25% likelihood of CC (0.25).• dd x Dd = 50% likelihood of dd (0.5).• Ee x ee = 50% likelihood of ee (0.5).• FF x Ff = 50% likelihood of FF (0.5).

• 0.5 * 1 * 0.25 * 0.5 * 0.5 * 0.5 = 0.015625 (1.5625%)http://img1.wikia.nocookie.net/__cb20110523221131/villains/images/6/66/Bowser_SMG.jpg

For more on probability…

• Head to the “Fact Sheets” section of my site and view the video:– Fact Sheet – Unit 5 – Genetics Probability

Practice

• Genetics Practice 2: Dihybrid Crosses worksheet• Genetics Practice 4: Probability worksheet

To Mendel…and beyond!

• As we know, Mendel got lucky with his pea plants since they tend to exhibit only one trait or another among the characteristics he studied.– This is called complete dominance (or sometimes

simple inheritance) – when one allele completely dominates another.

• As we know, there are a few more ways traits can be passed on. Let’s talk about them…

Patterns of Inheritance/Gene ExpressionSummary Slide

• Complete Dominance/Simple Inheritance• Incomplete Dominance• Codominance• Pleiotropy [gene expression]• Polygenic Inheritance• Multiple Alleles• Epistasis [gene expression]• Sex-Linked Inheritance

Inheritance Forms You Should Know

http://learn.genetics.utah.edu/content/begin/traits/

Complete Dominance

Incomplete Dominance

Codominance


• Incomplete dominance occurs when heterozygotes exhibit a blend or intermediate of the two homozygous traits.– Like if a red flower and a white flower make a pink

flower.– Like how a curly hair allele and a straight hair

allele make wavy hair.


• Incomplete dominance occurs when heterozygotes exhibit a blend or intermediate of the two homozygous traits.– Like if a red flower and a white

flower make a pink flower.– However, there is no pink allele.

• The ratios shown at the right are typical.

Incomplete DominancePunnett Squares

• You can still show incomplete dominance with a Punnett Square (two different ways).

• Method 1: (same allele letters, less common)

• Method 2 (different allele letters, more common)

Rr RrRr Rr

RR

r r

RW RWRW RW

RR

W W

Pink

Pink

Pink

Pink

Pink

Pink

Pink

Pink

Codominance

• Codominance occurs when heterozygotes display both phenotypes at the same time, but NOT as a blend.– For example, in the horses at the

right, the heterozygous horses are known as roan.

– Roan animals appear to be somewhere in between red and white because they have BOTH red and white hairs.• NOT pink.

Gratuitous Photo of Roan Cattle

http://www.ck12.org/ck12/images?id=149175

CodominancePunnett Squares

• Method 1: (different allele letters)

• Method 2 (same allele letters and superscripts)

RW RWRW RW

RR

W W

FRFW FRFW

FRFW FRFW

FR

FR

FW FWSp

ot s

Spot s

Spot s

Spot s

Spot s

Spot s

Spot s

Spot s

R = Red Flowers, r = White Flowers

Table of Phenotypes

Complete Dominance

Incomplete Dominance Codominance

RR

Rr

rr

R = Red Flowers, r = White Flowers

Table of Phenotypes

Complete Dominance

Incomplete Dominance Codominance

RR Red Red Red

Rr Red Pink Red/White Spots

rr White White White

Another Example of Codominance• Human blood type is a codominant trait.• The allele used for blood type is I or i.– I is dominant (in my font).– i is recessive (in my font).

• There are four types of human blood but only three alleles each coding for a particular protein on the blood cells:– A (has the IA allele)– B (has the IB allele)– O (has the i allele - no protein)

Blood Type• Each red blood cell has two receptors on it called antigens.• One is called H (the first floor), and the second one is

either A or B. O doesn’t have a second antigen.

http://lomalindahealth.org/health-library/graphics/images/en/19450.jpg

Aside: Bombay Type, et cetera

• Turns out there’s still another blood type.• “Bombay” type individuals have absolutely no

antigens. Not even the base level “H.”• Also, apes mostly have our blood type:– Chimpanzees only have Type A and Type O.– Gorillas only have Type B.

• Other animals don’t have similar blood types.• Cats have 3 different blood types, dogs have 12,

cattle have 11, pigs have 16, and horses have 34.

How is it inherited?

• IA and IB are both dominant. i is recessive.• So, anyone receiving two IA alleles or an IA and i

allele will have Type A blood.• The same goes for IB alleles producing Type B

blood.• Type O blood is produced by the ii genotype.• The last blood type, AB, is produced by one IA

allele and one IB allele, since they’re codominant.

What does it mean?

• Since Type O blood has only H antigens on it, it can be given to anyone.– We call it the Universal Donor (O-, technically).– Type O blood is also the most common, believe it or not.

• Since Type AB blood has both A and B antigens, people with type AB blood can receive any type.– We call it the Universal Acceptor (AB+, technically).– Type AB blood is also the least common.

Blood Compatibility

http://upload.wikimedia.org/wikipedia/commons/thumb/5/51/Blood_Compatibility.svg/230px-Blood_Compatibility.svg.png

There’s also this…

What If We Mix Blood?

• Well, a little mixed blood won’t hurt you, but getting a blood transfusion with the wrong type can be a big problem.

• Basically what happens is your body sees the wrong antigens on the cell and treats it like an invader, a pathogen.

• Your immune system’s antibodies destroy it, and in doing so it gets clumpy, a process called agglutination.– This helps white blood cells destroy the “invader.”

• Clumpy blood = ouch/death.• You can test unknown blood easily this way. How?

Antibodies and Antigens

• To fully understand blood typing, you need to understand antigens and antibodies.

• Antigens are protein identifiers on the outside of cells.

• Antibodies (immunoglobulins) are part of the immune system and neutralize pathogens by binding to specific antigens.– They’re also proteins.

• So antigens are antibody generators.

Antibodies and Antigens

http://www.nobelprize.org/educational/medicine/landsteiner/readmore.html

Blood Type AThese people

have A antigens on their blood cells and will generate B

antibodies to defend against

B invaders.

Blood Type BThese people

have B antigens on their blood cells and will generate A

antibodies to defend against

A invaders.

Blood Type ABThese people have A and B antigens on

their blood cells and will not

generate antibodies.

Blood Type OThese people have type no antigens on

their blood cells and will

generate A and B antibodies to defend against A/B invaders.

A Little More About Blood

• We often say blood is “O negative” or “A positive.”

• This (positive) means that their blood also expresses a particular Rh (Rhesus) antigen called D.– Negative means they don’t express it - about 15%

of people.• Here’s why it’s important…

Rh Factor

http://www.nobelprize.org/educational/medicine/landsteiner/readmore.html

Rh+ BloodThese people have Rh antigens (D) on

their blood cells and will not not

generate Rh antibodies.

Rh- BloodThese people have

no antigens on their blood cells

and will generate Rh antibodies to defend against

invaders.

Blood Donation

• So, Rh+ blood will prompt an immune response when inside people that have Rh- blood.– Therefore, you can’t give + to –.– However, – can be given to +.

http://nobelprize.org/educational_games/medicine/landsteiner/readmore.html

Rh Factor

• In pregnancy, blood sometimes “leaks” between the fetus’s circulatory system and the mother’s.

• The baby may have a different blood type from the mother.

• If the baby is Rh+ (means it makes this D antigen) and the mother is Rh- (means she doesn’t), the leakage of blood may cause the mother to make antibodies.– Her body sees this D antigen and treats it like an

invader (pathogen).

Rh Factor

• Normally, this wouldn’t matter; the fetus and mother should have separate blood vessels.

• Sometimes, however, mom’s blood “leaks” back across the placenta into the baby.– Mom’s D antibodies (the “police” of her blood) attack the

baby’s blood.– This is called erythroblastosis fetalis or hemolytic disease in

the newborn.– RhoGAM® is a drug available to treat Rh incompatibility.

http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/B/BloodGroups.html

Back to Blood Tests• Imagine a sample of unknown blood.• You also have known samples of antibodies for

Blood Type A, Blood Type B, and Rh Factor.• Take the unknown blood and mix it with the

antibodies.

A B

If the blood clumps in A, it’s A.

If the blood clumps in B, it’s B.

If the blood clumps in A and B, it’s AB.

If the blood clumps in neither, it’s O.

Rh

If it clumps in here, it’s positive.

?

Antiserum• Actual blood typing kits, like in the game we’re

about to play, use an antiserum (not actual blood).– An antiserum is the stuff that contains antibodies for

different blood types.• For example, B antiserum contains B antibodies and is

designed to clump in the presence of B antigens.• Put B antigens in there (as in, B blood cells) and you’ll get

agglutination, which is a match.

• Confused? Just remember this:– With actual blood, clumping occurs with incompatibility.– With antiserum, clumping occurs when there is a match.

Blood Type Game• Nobel Prize website for blood typing and

transfusions:– http://www.nobelprize.org/educational/

medicine/landsteiner/blood.swf

Drag the syringe to the patient’s arm to

draw blood.

Drag above the test tubes to add the

drawn blood.No match for B

Match for A Match for Rh (+)

Blood Type Game (New Version)

• Beware – lots of blood:– http://www.nobelprize.org/educational/

medicine/bloodtypinggame/game/blood_loader.swf

Match for B

No match for A

No match for Rh

Blood Type Game

• Donor Match Game (Are You My Type?)– http://www.redcrossblood.org/donating-blood/

donor-zone/games/blood-type– See accompanying worksheet.

A Look at Global Blood Types

http://en.wikipedia.org/wiki/Blood_type#ABO_and_Rh_distribution_by_country

Back to Blood Type Genetics

• The i allele is recessive here, and if it is paired with another i it produces blood type O.

• If it is paired with anything other than another i, it is “hidden,” or not expressed. The other allele is expressed.– That person becomes a “carrier” of the recessive (i) allele.

• If you get an i allele from your mom and an i allele from your dad, you wind up with the i i genotype, which we call Type O blood.

• Any other allele (IA or IB) will override the i allele.

Blood Types

• Here’s a table to summarize:

Parent 1 Parent 2 Offspring

Type O (i) Type O (i) Type O (i i)

Type A (IA) Type A (IA) Type A (IA IA)

Type B (IB) Type B (IB) Type B (IB IB)

Type A (IA) Type O (i) Type A (IA i)

Type B (IB) Type O (i) Type B (IB i)

Type A (IA) Type B (IB) Type AB (IA IB)

My Blood Type Punnett Square

• Dad has Type A Blood (IA i).– Heterozygous.

• Mom has Type O Blood (i i)– Set up the Punnett Square.

• What are the chances of a child:– With Type A blood?– With Type B blood?– With Type AB blood?– With Type O blood? (that’s me!)

http://www.thetech.org/genetics/ask.php?id=71

IAi x ii [ignore Rh]

IA i

Type Ai i

Type O

IA iType A

i iType O

i

i

IA iChances of A:50%Chances of B:0%Chances of AB:0%Chances of O:50%

Another Blood Type Punnett Square

• Dad has Type A- Blood (IA i).– Heterozygous.

• Mom has Type AB+ Blood (IA IB)– Set up the Punnett Square (antigens and Rh factor are

inherited independently).• What are the chances of a child:– With Type A blood?– With Type B blood?– With Type AB blood?– With Type O blood?

http://www.thetech.org/genetics/ask.php?id=71

IAi x IAIB [ignore Rh]

IAIA

Type AIAi

Type A

IAIB

Type ABIBi

Type B

IA

IB

IA iChances of A:50%Chances of B:25%Chances of AB:25%Chances of O:0%

Rh Factor in Punnett Squares

• For Rh Factor, positive (+) is dominant, negative (-) is recessive.– Someone with Rh+ blood could be ++ or +-.– If you don’t know what they are, you have to assume

they’re +- (heterozygous):- -

+ +- +-

- -- --

Putting It TogetherCross AB+ and A-

IA- i-

IA+ IAIA+ IAi+

IA- IAIA- IAi-

IB+ IAIB+ IBi+

IB- IAIB- IBi-

Aside: What Makes Red Blood Cells?

• Bone marrow!

http://sicklecellbodypolitics.files.wordpress.com/2011/04/bonemarrow2.jpghttp://www.nlm.nih.gov/medlineplus/magazine/issues/summer11/images/boneAnatomy-lg.png

Pleiotropy and Polygenic InheritanceGene Expression

• Pleiotropy occurs when one gene affects multiple traits.– Usually a result of disease in humans.– Example: Sickle-cell anemia.

• Single gene mutation leads to heart failure, spleen/brain damage, et cetera.

• Polygenic inheritence occurs when multiple genes affect one trait.– Usually shows phenotypes on a continuum (not “either-or”)

with the most common phenotype in the middle.– Example: Skin color, height, weight, high blood pressure.

• Risk factors from different genes (weight, blood vessel rigidity, etc).

For more on skin color…

• TED: Nina Jablonski – Skin Color is an Illusion

Pleoitropy

Polygenic Inheritance

Multiple Alleles

• Multiple allele inheritance occurs when there are more than two alleles possible for a given trait.

EpistasisGene Expression

• Epistasis occurs when one GENE completely hides another GENE.– We’re not talking about alleles

here.• For example, in mice, one gene

controls pigment color…– Brown or black.

• …while another gene controls albinism.– If you’re albino, it doesn’t matter

whether you get the brown or black allele. You’re white.

Other? (Nature versus Nurture)

• Keep in mind, genetics are not the only thing influencing phenotypes.

• If you don’t have a genetic family history of high blood pressure, for example, you can still get it if you eat only Reese’s Spreads for a lifetime.

• Other examples?– Skin tone (influenced by UV radiation).– Arctic fox coat color (influenced by heat-

sensitive genes).– Plants that develop different flower color

due to soil conditions.

Case in Point: Tan Mom

• Patricia “Tan Mom” Krentcil’s genes don’t produce her skin tone phenotype. It’s entirely “environmental.”

• Consequently, her child won’t be “reanimated corpsish” despite being her offspring.

http://media.nj.com/ledgerupdates_impact/photo/2012/05/10933313-large.jpghttp://1.bp.blogspot.com/-HnKpQcqEk_g/T7XAtYqOD5I/AAAAAAAAAkc/bJjMb008ObI/s400/tan+mom.jpghttp://itsybitsysteps.com/wp-content/uploads/2013/04/tan-mom-patricia-krentcil-daughter.jpg

Other? (Nature versus Nurture)

• Since these traits are both inherited and acquired…– …that’s a little Lamarckian, huh?

• …we call them multifactorial.• There’s also the [separate] concept of penetrance.– Penetrance is a way to see exactly how “strong” a gene

is.– 100% penetrance of a disease allele, let’s say, means that

everyone with that allele has the disease.– 50% penetrance of a disease allele means that only half

of all individuals with the allele show clinical signs.• It’s usually used for dominant alleles.

Other?

• Yet another pseudo-inheritance pattern:• Genomic imprinting occurs when one of the two

alleles for each gene inherited from our parents is “epigenetically silenced.”– In other words, only one allele is working properly.

• This is done through methylation – we’ll talk about it another day.

Practice

• Genetics Practice 3: Advanced Mendelian Genetics worksheet

Sex-Linked Genes

• Sex-linked genes are genes found on the sex chromosomes (you know, X and X/Y).

• They are not necessarily related to gender.• Most appear only on the X chromosome.– As a result, sometimes these traits/genes are called X-linked.– The X chromosome has about 800-900 genes, but only a few

are related to sex-characteristics.– The Y chromosome has nearly only male sex-related genes

(and about 40 genes).• Examples:– Colorblindness– Hemophilia (disorder where blood doesn’t clot easily)

Male Sex-Linked Alleles

• X and Y are not equal chromosomes.

• Most genes on the X chromosome are not duplicated on the Y chromosome.– Therefore only one allele is

present in males.– Only one allele necessary for a

dominant or recessive phenotype.

http://www.chessieinfo.net/user/cimage/XY.jpg

Sex-Linked Genes

• To put it another way, suppose I had you playing a game.

• The goal of the game is to flip a coin and get heads.

• Males get to flip once; females twice.• Who’s more likely to lose?– The same goes for sex-linked traits.– Males, with only one X chromosome, get only one

shot at dodging sex-linked disorders. Females get two.

Sex-Linked Genes and Punnett Squares

• To do a Punnett Square with a sex-linked gene, pick an allele letter just like normal, but put it on the appropriate sex chromosome.

• Example next slide…


• Having normal vision (N) is dominant to having colorblind vision (n).– A woman homozygous dominant for normal vision

would be XN XN.– A woman heterozygous (carrier for colorblindness)

for normal vision would be XN Xn.– A woman homozygous recessive (colorblind)

would be Xn Xn.


• Having normal vision (N) is dominant to having colorblind vision (n).– A man that is normal would be XNY; colorblind would be XnY.

• Fun fact: Because men don’t have two alleles, they’re called hemizygous (either affected or not).

• Genes found on the Y chromosome are holandric (or Y-linked).– They’re passed from father to son.

• One important Y-linked gene is SRY.– Sex-determining region of the Y chromosome.– SRY’s activation in development prevents the development of

ovaries and leads to the activation of other male-making genes.


Colorblind Male →

Xn YNormal (Heterozygous) Female ↓

XN XNXnNormal (heterozygous) female

XNYNormal male

Xn XnXnColorblind female (RARE!)

XnYColorblind male


• If this couple had a child, it would have a:– 25% chance (1/4) of being a normal female.• But a carrier of the colorblindness allele.

– 25% chance (1/4) of being a colorblind female.• Rare because it takes two recessive alleles as a female.

– 25% chance (1/4) of being a normal male.– 25% chance (1/4) of being a colorblind male.• More common than colorblind females because even

just one recessive allele leads to colorblindness.

Let’s try another…

• Try crossing a normal vision female (heterozygous) with a normal vision male (hemizygous unaffected).


Normal Male →

XN YNormal (Heterozygous) Female ↓

XN XNXNNormal (homozygous) female

XNYNormal male

Xn XNXnNormal female (carrier)

XnYColorblind male

Notice: Neither parent is colorblind, but one in four children (one in two males) from this couple will be colorblind, and it is an allele passed from Mom.

Colorblindness in America

• By the way, in this country, estimates show that 7% of males are colorblind in the most common way (red/green colorblind).

• On the other hand, only 0.4% of females are red/green colorblind.– Why? Because it’s a sex-linked (X-linked) gene!

Colorblindness

• To have a female that is colorblind, her mother must have been at least a carrier, and her father had to have been colorblind too.

• To have a male that is colorblind, all that’s needed is a mother that’s at least a carrier.– If you are a colorblind male, it was an allele passed

from your Mom. Dad gave you the Y chromosome, remember?

One last thing on sex-linked genes…

• Remember how one X chromosome gets inactivated in females’ somatic cells?– It’s called a Barr body?

• Well, it’s not the same X chromosome in every cell. The chromosomes are inactivated randomly.

• That means that females express different genes in different cells.– Thus, a female that is a carrier for colorblindness (but

doesn’t “show” it), actually MAY BE colorblind in some of her cells.

X Chromosome Inactivation


https://upload.wikimedia.org/wikipedia/commons/0/03/Heterochromia_iridum_and_iridus_2013-09-30_14-15.jpg


• We call this concept of having regions of effectively different cells mosaicism.

• For more:– Veritasium – Why Women are Stripey

Practice

• Genetics Practice 5: Sex-Linked Traits worksheet

Brain Break

• Conan O’Brien – If They Mated

“Skipping a Generation”

• Some traits appear to “skip a generation.” In other words, they’ll appear in a child and his grandparents, but not his parents.

• This is usually a result of sex-linked genes, and frequently can be traced via the maternal (mother) side of the family.– It’s also usually from a recessive allele.


• Imagine colorblindness (again).• A colorblind male (we’ll call

him Grandpa) has children with an unaffected female.– 50% Chance of Carrier Daughter– 50% Chance of Unaffected Son• Let’s watch one of the carrier

daughters.

http://ghr.nlm.nih.gov/handbook/illustrations/xlinkrecessivefather.jpg


• She grows up.• She then has children

with an unaffected male.– 25% chance of unaffected

son.– 25% chance of unaffected

daughter.– 25% chance of carrier

daughter.– 25% chance of affected

son.

http://www.discern-genetics.org/images/6.5.gif

Phew.

• Wow. That’s a lot.• Have you any questions?• None? Really?– Not even a nice, “How’s your day goin’, Mr. G?”• We’re talking about genetics. Of course it’s goin’ well.

• Okay then, let’s do a little whiteboard activity.• I’ll show you an image, you tell me what kind

of inheritance it is.

Which type of inheritance?

Codominance


Complete Dominance(or possibly polygenic)


Complete Dominance(with epistasis if the one

on the right is albino)


Sex-Linked


Complete Dominance(or possibly polygenic)


Incomplete Dominance(with epistasis)


Codominance


Complete Dominance


Codominance


Codominance and Multiple Alleles


Codominance andSex-Linked

Calico Cats

• “Calico” is just a name for a color pattern involving orange, black, and white on cats.

• Cats with these colors are nearly always female because the gene for orange or black fur is X-linked.– Thus, males can have either the allele for orange

OR black, but not both. Females can have both.• The gene for the white fur is not X-linked.


Multiple Alleles and [maybe] Incomplete Dominance


Multiple Alleles and Codominance


Polygenic

Just for fun…

• Because I couldn’t resist:

Studying Inheritance

• Remember when I mentioned “genetic family history” earlier in this PowerPoint?– No? Well I did. Pfft.

• A “genetic family history,” once formally drawn out, is known as a pedigree.– Pedigrees make it easy to look at the way genes are

passed through large families.• Vertical lines represent offspring and new

generations.• Horizontal lines show marriage/crosses and

related siblings.

Sample Pedigree

• In this, and most examples, males are squares and females are circles. – Probably easy to

remember.• First generation at the

top, newer below.

Sample Pedigree

• “Affected” individuals have filled-in shapes.– In other words,

pedigrees only look at one particular phenotype, not multiple traits or genotypes.

• Carriers tend to be half-shaded (but not always).

Pedigree Practice Problems

In this pedigree, sickle cell anemia (a) is recessive to wild type blood (A). Give the genotypes for each of

the individuals shown.(blue is “affected”)

1 2

43

Aa aa

Aaaa


Does this pedigree illustrate a dominant or recessive trait? (blue is shaded)

Think carefully!Use Punnett Squares!

Italics!

1 2

4 53


• This trait could be dominant or recessive.

Rr rr

Rr RrRr

Dominant Recessive

rr Rr

rr rrrr

Using a Pedigree

• Look at this portion of a full pedigree:

• Could this pedigree possibly illustrate a dominant trait?– Why or why not?

This pedigree could not

illustrate a dominant trait

because neither parent has a

dominant allele.

1 2

43

bb bb

bbB?

Using a Pedigree• Look at this portion of a full pedigree:

• Could this pedigree possibly illustrate a dominant or recessive trait?– Why or why not?

This pedigree could illustrate a

dominant or recessive trait

because one of the parents and offspring express

the trait.

1 2

43

Bb bb

Bbbb

Recessive

bb Bb

bbBb

Dominant

Other Pedigree Examples

Sex-Linked Traits and Pedigrees

• This is a big pedigree. Where do we start?– First, some highlights:– See “JC” over on the right side? That’s the current king

of Spain, Juan Carlos.– Locate Olga, Tatiana, Marie, Anastasia, and Alexei near

the middle of the pedigree. Then look at their parents. Recognize them?• P.S. The whole Romanov family was executed in 1918 – the kids

were between 13 and 22 years of age at the time.

– Find Prince Charles in the lower left. His wife was Princess Diana. Their son is Prince William (of Royal Wedding fame).

Royal Family Pedigree

• One more weird relationship in this pedigree:• Anastasia Romanov, daughter of Czar Nicholas II and

his wife Alix, was long thought to have escaped execution along with her brother Alexei (the hemophiliac).– Indeed, though the other skeletons were found long

after the execution, theirs originally were not.• To add to the confusion, years later a woman

named Anna Anderson claimed to be Anastasia, but was cremated.

Royal Family Pedigree

• Thanks to mitochondrial DNA, however, not only was Anna Anderson not Anastasia (she was a Polish woman named Franzisca Schanzkowska), but two partially burned skeletons in 2007 were Alexei and Anastasia.

• How did they confirm this?• With mitochondria DNA (mtDNA), compared to a

sample submitted by Prince Philip – Queen Elizabeth II’s husband – who shares the same maternal mitochondrial DNA as the Romanovs.

• Key: mtDNA and other genes found outside the nucleus are known as “extranuclear genes.”

Extranuclear Diseases?

• The following is a brief list of mtDNA-related diseases:– Leber hereditary optic neuropathy (LHON)– Pearson syndrome– Leigh syndrome– Pyruvate dehydrogenase complex deficiency

(PDCD/PDH)– Progressive external opthalmoplegia

But then there’s Queen Victoria

• She’s the second “Victoria” from the top.

• Reigned from 1837 to 1901.– That’s 63 years!

• 9 children, 42 grandchildren.

• Carrier of hemophilia.

http://en.wikipedia.org/wiki/Victoria_of_the_United_Kingdom

Hemophilia

• Queen Victoria was a carrier (through mutation) of the gene for hemophilia.

• Hemophilia is a blood disorder in which clotting is slow to occur and “bleeding out” is likely. Larger wounds can be fatal.

• The gene is recessive, and is on the X-chromosome.– Thus, sex-linked (or X-linked).

Aside: X-Inactivation (Lyon Law)• Females inactivate one of their X chromosomes (making it a Barr body).• This happens in the embryo stage on a cell-by-cell basis – it’s not the

same one for each cell.– Also interesting – early in post-zygotic development, only the paternal X

chromosome is inactivated. Then it’s reactivated, only to be [possibly] randomly deactivated again.

– This is not the case for marsupials – they always inactivate Dad’s X.• Most, but not all, of the X chromosome’s genes are dormant, and the

ones that are working are generally the same as those on the Y chromosome that don’t have to do with gender.

• In this way, carrier females may still be actively using the hemophilia (or whichever) gene, meaning that some of their cells actually are hemophiliac, but that they have a minimum number of working cells to keep them seeming apparently normal.– Victoria may have inherited the disease this way. Hard to say…

Other Pedigrees

Answers to the Previous Slide

• Q6– 5 are heterozygous.• All shaded/affected individuals (tasters).

– 11 are homozygous (all homozygous recessive).• All unaffected individuals (non-tasters).

• Q7– 50% (cross is Tt x tt).

Pedigrees: Take-Away Points

• The big thing to note about pedigrees is that you can analyze the nature of a gene/allele without actually running complicated genetics tests.

• While the difference between dominant and recessive autosomal traits varies by pedigree, sex-linked traits can be identified if mainly only males are getting them.– Remember, males have only one X chromosome, so

they only have “one shot” at getting an allele that overrides the condition.

Practice

• Genetics Practice 6: Pedigrees worksheet

Why go to all the trouble?

• Like you might (ever so existentially) ask about regular family trees, why do we even bother with pedigrees?

• It’s because it provides us a history, and history always provides us one thing:– A lesson.

• Pedigrees in the modern era allow us to begin opening the field of genetic counseling.

Genetic Counseling

• Many diseases are able to be identified from a karyotype:– Tay-Sachs– Sickle-cell anemia– PKU– Albinism– Cystic Fibrosis

• By doing two common tests…– Amniocentesis (amnio)– Chorionic villus sampling (CVS)

• …we can inform parents-to-be about their child’s traits.

Amnio/CVS

Cystic Fibrosis

• In normal cells, chloride ion channels move Cl- ions to the extracellular matrix, causing water to move by osmosis.

• In cystic fibrosis, those Cl- channels stop working and mucus begins to build up.

• That mucus can then block air sacs in the lungs and ducts throughout the body.– The channels are called CFTR

channels – cystic fibrosis transmembrane conductance regulator.

Cystic Fibrosis

• How is it inherited? A three-nucleotide sequence is deleted from a gene (CFTR) on Chromosome 7.

• 1 in 25 Caucasians is a carrier (1 in 2500 births = CF).• Life span is ~25 years with treatment (<5 without).

Tay-Sachs

• 1 in 3600 births, but the odds are 100x greater in Ashkenazic Jews and Cajuns.– Founder effect, perhaps?

• A broken enzyme fails to break down lipids in brain cells.

• Seizures, blindness, degeneration of motor skills, and finally death occur usually before age 5.

Sickle-Cell Anemia

• Mostly present in people of African descent:– 1 in 400 individuals.

• A single nucleotide causes valine to be substituted for glutamate.

• Sickle-cell also provides a way to introduce and review a few topics.

Sickle-Cell New and Review

• Cell sickling leads to pleiotropic effects.

• Being homozygous dominant is lethal dominant, where individuals die of the disease.

• Being homozygous recessive is normal but leaves you susceptible to malaria (see photo).

• Being heterozygous is therefore sometimes best (heterozygote advantage).

What about dominant diseases?

• It’s important to know that dominant alleles are NOT necessarily more common than recessive alleles.

• Take, for example, Huntington’s disease.– It’s a degenerative neurological disease caused by a

dominant allele.– The allele is near the end of chromosome 4 and in affected

individuals features a long repeating section of “CAG” nucleotides.

• Those with the disease suffer a buildup of a mal-formed protein called Huntingtin in the brain, which ultimately leads to muscle tremors and death.

Dominant Diseases

• Achondroplasia (“without cartilage formation”) is a form of dwarfism caused by a dominant allele.– The FGFR3 gene.

• No [dominant] achondroplasia alleles and you’ll be of normal stature.

• One [dominant] achondroplasia allele causes dwarfism.• Two [dominant] achondroplasia alleles?– You’re dead. Bones don’t lengthen properly and stillbirth is

common.– This is a “lethal dominant” inheritance pattern.

http://ghr.nlm.nih.gov/condition/achondroplasia

The dark side?

• There’s a scarier side to this genetic testing.• Like all powerful things, it can (and should) be used

for good.• It can also make life significantly more complicated.• For example, would you want insurance companies to

base their premiums (rates) on your genetic “predispositions?”

• Do we need to label food that is genetically modified?• For more:– TED: Paul Wolpe – Questioning Bioengineering

Final [Normal] Inheritance Topic

• The last thing we need to talk about in the course of normal inheritance patterns is the idea of linked genes.– Linked genes are those that are found near one

another on the chromosomes.– Because they’re close to one another, they tend to

get passed on together, even through events like crossing over (synapsis).

Linked Genes

• The topic of linked genes was discovered by William Bateson and Reginald Punnett.– Yes, that Punnett. Dude was awesome.

• The idea is this:– Crossing over randomly mixes-and-matches alleles.– If, however, two alleles are located near one another on a

chromosome, the likelihood that they will be separated during crossing over is low.

http://dnaftb.org

Reginald Punnett

William Bateson

Linked Genes

• In other words…

Linked Genes

• Thus, the offspring of any cross may be:– Parental types, in that they inherit one of the two

parents’ phenotypes.– Recombinant types, in that they do not resemble

either parent’s phenotypes.• Key: When genes are linked, parental types are

more likely.• Key: Crossing over creates recombinant

chromosomes/gametes.– Remember?

Linked Genes

Linked Genes: Gene Mapping

• So how do we know how close genes are to one another?

• We can use test crosses to gather recombination frequencies.– The higher the frequency, the further the genes are.

• By doing enough testing, we can create a genetic map showing all genes’ loci.– Such genetic maps (linkage maps) use a 1% recombination

frequency as 1 map unit.• This is best understood with images.– Key: Recombination increases with increasing distance.

Linked Genes: Gene Mapping

Linked Genes Practice Problems

• Suppose test cross data indicates that Gene A and Gene B have a recombination frequency of 15%, Gene B and Gene C have a recombination frequency of 9%, and Gene A and Gene C have a recombination frequency of 24%.

• What is the order of genes on the chromosome?

A B C15% 9%

24%

Linked Genes Practice Problems

• What if the recombination frequency between A and C is 6% (not 24%)?

• What is the order of genes on the chromosome?

A C B6% 9%

15%

For more on linked genes…

• Head to the “Fact Sheets” section of my site and view the video:– Fact Sheet – Unit 5 – Linked Genes

There’s something missing…

• Well over 180 slides and we still haven’t yet discussed something essential to evolution.

• It’s also not analyzed with any Punnett square.• About what am I talking?– Mutations.

• Note: We’ll talk about chromosome-level mutations now but you will learn about a bunch more next unit on the DNA/nucleotide level.

Chromosome-Level MutationsSummary Slide

• Nondisjunction• Deletion– Part of the chromosome is removed.

• Duplication– Part of the chromosome is copied.

• Inversion– Part of the chromosome is flipped.

• Translocation– Part of the chromosome is moved.

Nondisjunction

• Nondisjunction basically means the chromosomes didn’t come apart properly in meiosis.– Nondisjunction is the cause of Down Syndrome and related

aneuploid defects.

• It occurs when, during metaphase and anaphase:– The spindles attach to the wrong set of chromosomes, so they’re not

split evenly OR

– The centromeres do not divide properly, sending too much DNA one way and too little the other way.

• Animation:– http://www.biostudio.com/d_%20Meiotic%20Nondisjunction%20Me

iosis%20I.htm

http://www.biostudio.com/d_%20Meiotic%20Nondisjunction%20Meiosis%20I.htm

http://www.biostudio.com/d_%20Meiotic%20Nondisjunction%20Meiosis%20I.htm

Nondisjunction (Meiosis I)

46

24 22

Start meiosis with one diploid cell that has 46

chromosomes.

24 24 22 22

End with sperm or egg cells that have the wrong

number of chromosomes.

NONDISJUNCTION

Nondisjunction (Meiosis II)

46

23 23

Start meiosis with one diploid cell that has 46

chromosomes.

23 23 24 22

End with sperm or egg cells that have the wrong

number of chromosomes.

NONDISJUNCTION

Nondisjunction: Down Syndrome

Nondisjunction: Klinefelter Syndrome

Deletion: Cri-du-chat Syndrome

• Cri-du-chat (“Cat’s Cry”) – a deletion of part of chromosome 5.• Among delayed development, disfigurement, and possible

heart defects, cri-du-chat syndrome leads to poor larynx development and a high-pitched “cat’s cry.”

Duplication: Fragile X Syndrome

• A nucleotide sequence of CGG repeats so much that it inhibits neighboring genes, leading to mental disabilities.

http://24.media.tumblr.com/tumblr_m4ibogtnqU1rq3lp6o1_500.gif

Deletion/DuplicationInversion/Translocation

Translocation• During crossing over, a part of a chromosome winds up on

another, non-homologous chromosome.• Occurs in, among other things, CML (chronic mylogenous

leukemia).– In CML, Chromosome 22 is almost wholly removed, leaving something

called the “Philadelphia chromosome.”

http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/M/Mutations.html

Translocation Analogy

• Imagine you’ve got two copies of the same book (let’s say, the dictionary).

• If you tore out the last 50 pages of each and put them in the other book, you’d still have a complete dictionary.– That’s normal crossing-over.

• However, if you took the dictionary and the autobiography of Mickey Mouse, you’d end up with two very jumbled endings.– That’s translocation.

The Last Word

• Keep in mind, none of those mutations really have any impact on an offspring unless they happen in a gamete.

• Somatic cell mutations are not heritable.

Last Practice

• Genetics Practice 7: Patterns of Inheritance

Closure

• Genetics WhipAround – this should be a good one…

• Write down 4 things (and explanations) from this lesson and stand up when you’re done.

today is monday, december 8 th, 2014 pre-class: who’s your daddy, genetics? tell your neighbor...

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