Transcript AND “B”

In This Lesson:
Mendelian
Genetics and
Heredity
(Lesson 3 of 3)
Today is Tuesday,
th
December 6 , 2016
Pre-Class:
Who’s your daddy, genetics?
Tell your neighbor something
about him.
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 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?
Mendel’s Generations
• 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
G
GG
G
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.
g
gg
g
G
Gg
g
Mendel’s Laws
G
GG
G
2. Law of Independent
Assortment
– The segregation process of
metaphase I is random.
• Remember that?
g
gg
g
– NOTE that there are exceptions
to this rule that we will discuss
later.
G
Gg
g
Mendel’s Laws
GG
3. Law of Dominance
– Some alleles/traits are
dominant to others.
• Remember that?
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.
G
Gg
g
Test Cross
• As we learned way back when we did HardyWeinberg, 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]
DdHh
Outer
First
Last
Inner
Possible Allele
Combinations
DH
Dh
dH
dh
DdHh x DdHh
9:3:3:1
DH
Dh
dH
dh
DH
DDHH
DDHh
DdHH
DdHh
Dh
DDHh
DDhh
DdHh
Ddhh
dH
DdHH
DdHh
ddHH
ddHh
dh
DdHh
Ddhh
ddHh
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?
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 Multiplication
Genetics 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.
D
d
D
DD
Dd
d
Dd
dd
 75% chance of D
H
75% chance of H  h
H
HH
Hh
• 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?
h
Hh
hh
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.
C
c
C
CC
Cc
C
CC
Cc
A
a
B
b
A
AA
Aa
B
BB
Bb
– So, 0.5 * 0.5 * 0.5 = 0.125, or 12.5%, or 1 in 8.
a
Aa
aa
B
BB
Bb
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 Addition
Genetics 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 Expression
Summary 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
Complete Dominance
Incomplete Dominance
http://learn.genetics.utah.edu/content/begin/traits/
Codominance
Incomplete Dominance
• 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.
Mendel’s Generations
• 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 Dominance
Punnett Squares
r
Rr
Rr
Pink Pink
R
R
r
Rr
Rr
Pink Pink
• You can still show incomplete dominance with a
Punnett Square (two different ways).
• Method 1: (same allele letters, less common)
W
RW
RW
Pink Pink
R
R
W
RW
RW
Pink Pink
• Method 2 (different allele letters, more common)
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
Codominance
Punnett Squares
W
RW
RW
Spots Spots
R
R
W
RW
RW
Spots Spots
• Method 1: (different allele letters)
FW
FR FW
FR FW
Spots Spots
FR
FR
FW
FR FW
FR FW
Spots Spots
• Method 2 (same allele letters and superscripts)
R = Red Flowers, r = White Flowers
Table of
Phenotypes
RR
Rr
rr
Complete
Dominance
Incomplete
Dominance
Codominance
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 additional 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
Blood Type A
These people
have A antigens
on their blood
cells and will
generate B
antibodies to
defend against
B invaders.
Blood Type B
These people
have B antigens
on their blood
cells and will
generate A
antibodies to
defend against
A invaders.
http://www.nobelprize.org/educational/medicine/landsteiner/readmore.html
Blood Type AB
These people
have A and B
antigens on
their blood cells
and will not
generate
antibodies.
Blood Type O
These 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
Rh+ Blood
These people have
Rh antigens (D) on
their blood cells
and will not
generate Rh
antibodies.
Rh- Blood
These people have
no antigens on
their blood cells
and will generate
Rh antibodies to
defend against
invaders.
http://www.nobelprize.org/educational/medicine/landsteiner/readmore.html
Blood Donation
• So, Rh+ blood will prompt an
immune response when
inside people that have Rhblood.
– 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
Rh
If the blood
If the
clumps
blood
If the
inclumps
bloodinclumps
If it clumps
in in here,
A, it’sAneither,
A.
and B, it’s
it’s AB.
O.
B, it’s B. 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.
DragMatch
above for
theAtestMatch for
tubes to add the Rh (+)
drawnNo
blood.
match for B
Blood Type Game (New Version)
• Beware – lots of blood:
– http://www.nobelprize.org/educational/medicine
/bloodtypinggame/game/blood_loader.swf
No match
for A
No match
for Rh
Match for B
Blood Type Game
• Donor Match Game (Are You My Type?)
– http://www.redcrossblood.org/donatingblood/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
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]
i
i
A
I
i
IA i
Type A
IA i
Type A
ii
Type O
ii
Type O
Chances 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]
A
I
B
I
A
I
i
IAIA
Type A
IAIB
Type AB
IAi
Type A
IBi
Type B
Chances 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 Together
Cross 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://www.nlm.nih.gov/medlineplus/magazine/issues/summer11/images/boneAnatomy-lg.png
http://sicklecellbodypolitics.files.wordpress.com/2011/04/bonemarrow2.jpg
Pleiotropy and Polygenic Inheritance
Gene 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.
Epistasis
Gene 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 heatsensitive 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://itsybitsysteps.com/wp-content/uploads/2013/04/tan-mom-patricia-krentcil-daughter.jpg
http://1.bp.blogspot.com/-HnKpQcqEk_g/T7XAtYqOD5I/AAAAAAAAAkc/bJjMb008ObI/s400/tan+mom.jpg
http://media.nj.com/ledgerupdates_impact/photo/2012/05/10933313-large.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 Xlinked.
– 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…
Sex-Linked Genes and Punnett Squares
• Having normal vision (N) is dominant to
having colorblind vision (n).
– A woman homozygous dominant for normal vision
would be XNXN.
– A woman heterozygous (carrier for colorblindness)
for normal vision would be XNXn.
– A woman homozygous recessive (colorblind)
would be XnXn.
Sex-Linked Genes and Punnett Squares
• 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 Ylinked).
– 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.
Sex-Linked Genes and Punnett Squares
Colorblind Male →
Normal (Heterozygous)
Female ↓
XN
n
X
n
X
Y
N
n
X X
N
X Y
Normal (heterozygous) female
Normal male
XnXn
n
XY
Colorblind female (RARE!)
Colorblind male
Sex-Linked Genes and Punnett Squares
• 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).
• You’ll notice in my answer I’m going to use a
slightly different notation, but the meaning is
the same.
Sex-Linked Genes and Punnett Squares
Normal Male →
Normal (Heterozygous)
Female ↓
X
’
X
X
Y
XX
XY
Normal (homozygous) female
Normal male
XX’
’
XY
Normal female (carrier)
Colorblind 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
X Chromosome Inactivation
https://upload.wikimedia.org/wikipedia/commons/0/03/Heterochromia_iridum_and_iridus_2013-09-30_14-15.jpg
X Chromosome Inactivation
• We call this concept of having regions of
genetically 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.
“Skipping a Generation”
• 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
“Skipping a Generation”
• 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
Which type of inheritance?
Complete Dominance
(or possibly polygenic)
Which type of inheritance?
Complete Dominance
(with epistasis if the one
on the right is albino)
Which type of inheritance?
Sex-Linked
Which type of inheritance?
Incomplete Dominance
Which type of inheritance?
Complete Dominance
(or possibly polygenic)
Which type of inheritance?
Incomplete Dominance
(with epistasis)
Which type of inheritance?
Codominance
Which type of inheritance?
Incomplete Dominance
Which type of inheritance?
Complete Dominance
Which type of inheritance?
Complete Dominance
Which type of inheritance?
Codominance
Which type of inheritance?
Incomplete Dominance
Which type of inheritance?
Codominance and
Multiple Alleles
Which type of inheritance?
Codominance and
Sex-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.
Which type of inheritance?
Multiple Alleles and [maybe]
Incomplete Dominance
Which type of inheritance?
Multiple Alleles and
Codominance
Which type of inheritance?
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 halfshaded (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”)
Aa
1
aa
2
aa
3
Aa
4
Pedigree Practice Problems
Does this pedigree illustrate
a dominant or recessive
trait? (blue is shaded)
Think carefully!
Use Punnett Squares!
Italics!
2
1
3
4
5
Pedigree Practice Problems
• This trait could be dominant or recessive.
Recessive
Dominant
Rr
rr
Rr Rr Rr
Rr
rr
rr
rr
rr
Using a Pedigree
• Look at this portion of a full pedigree:
bb
1
bb
2
B?
3
bb
4
This pedigree
could not
illustrate a
dominant trait
because neither
parent has a
dominant allele.
• Could this pedigree possibly illustrate a dominant trait?
– Why or why not?
Using a Pedigree
• Look at this portion of a full pedigree:
Bb 1 bb 2 bb
Recessive
bb 3 Bb 4 Bb
Bb
Dominant
bb
This pedigree
could illustrate a
dominant or
recessive trait
because one of
the parents and
offspring express
the trait.
• Could this pedigree possibly illustrate a dominant or recessive
trait?
– Why or why not?
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 former king
of Spain, Juan Carlos (abdicated in 2014).
– 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 burned
skeletons found 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…
http://amnh.mrooms.net/mod/page/view.php?id=38663
Other Pedigrees
http://1.bp.blogspot.com/-KZtTHgTZhSA/UZG73jom5_I/AAAAAAAABrM/tte0aTmq7zE/s1600/DarwinPedigree.gif
Other Pedigrees
Other Pedigrees
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 Clchannels 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 malformed 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
– Disney Geneticists Debut New Child Stars
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
Reginald
Punnett
William
Bateson
• 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
Linked Genes
• The image to the right uses
T.H. Morgan’s notation for
fruit fly genes.
– In the image, b+ means “wild
type,” and b stands for “black
body.”
– Similarly, vg+ means “normal
wings” and vg means
“vestigial wings.”
• Since those genes are
linked, the offspring tend
not to get b+ and vg.
– Instead, the offspring get one
of the parents’
combinations.
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.
• Example:
– One parent has brown hair, brown eyes.
– One parent has blond hair, blue eyes.
• Parental Types: Offspring with brown hair and brown eyes OR
blond hair and blue eyes.
• Recombinant Types: Offspring with brown hair and blue eyes
OR blond hair and brown eyes.
Da Important Stuffz
• Key: When genes are linked, parental types
are more likely.
• Key: Linked genes DO NOT follow the
independent assortment rules of a typical
Punnett square (especially dihybrids).
• Key: Crossing over creates recombinant
chromosomes/gametes.
– ‘member?
Recombinant Chromosomes?
http://evolution.gs.washington.edu/module1/images/crossingover.jpg
Linked Genes
Explanation of Previous Slide
• A gray/normal fly
(heterozygous) is crossed
with a black/vestigial
(recessive) individual.
– Gray/normal wings is the wild
type for this fly.
• Instead of the vg+ system,
let’s imagine it as:
– GgNn x ggnn
• Do a dihybrid Punnett
square analysis:
g
g
G
Gg
Gg
g
gg
gg
n
n
N
Nn
Nn
n
nn
nn
Results:
25% chance of gray/normal
25% chance of gray/vestigial
25% chance of black/normal
25% chance of black/vestigial
But wait!
https://lh5.ggpht.com/NUL7VzLYOCsrb6_gXr7tq5QmFSMECEEdRvscGRIHSzAHL4N_Msljcs2Q99gX2Xfiq38=w300
http://upload.wikimedia.org/wikipedia/commons/b/b9/Goats_butting_heads.jpg
Compare the results…
• Notice that the Punnett
square results are not
consistent with the actual
results.
• Why? The genes are linked!
Results:
25% chance of gray/normal
25% chance of gray/vestigial
25% chance of black/normal
25% chance of black/vestigial
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 apart 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 (also called a centimorgan).
• This is best understood with images.
– Key: Recombination increases with increasing distance.
Linked Genes: Gene Mapping
Linked Genes: Gene Mapping
Linked Genes: Gene Mapping
Linked Genes Practice Problems
• Suppose you’re doing a test cross between a
fruit fly that is wild type and a fly that has
white eyes and vestigial wings.
• If, out of 1422 total offspring, 911 of them are
wild type and 221 are white-eyed/vestigialwinged, what is the recombination frequency?
– Well, if 911+221=1132 out of 1422 are parental
types, that means the remaining 290 are
recombinant types. 290/1422 = 20.39%.
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?
15%
A
9%
B
24%
C
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?
6%
A
9%
C
B
15%
• Note: Sometimes it’s possible to explain things
another way, given the numbers. As an example…
Linked Genes Practice Problems
• A series of fruit fly matings shows that the
recombination frequency between the gene for
wing size and the gene for antenna length is 5%.
The recombination frequency between the gene
for color and the gene for wing size is 10%.
• What is the order of genes on the chromosome?
Wing
5%
5%
Antenna
Color
10%
Antenna
5%
10%
Wing
15%
Color
Linked Genes Practice Problems
• Determine the
sequence of genes
along a chromosome
based on the
following
recombination
frequencies:
17
C
•
•
•
•
•
A↔B: 15 map units
A↔C: 17 map units
A↔D: 22 map units
B↔C: 32 map units
B↔D: 7 map units
15
7
A
B
22
32
D
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…
• 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 Mutations
Summary Slide
• Nondisjunction
– (will explain soon)
• 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.
– This is the cause of Down Syndrome and other aneuploid
defects.
– It could happen in mitosis, but probably without much effect.
• 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%
20Meiosis%20I.htm
Nondisjunction (Meiosis I)
Start meiosis with one
diploid cell that has 46
chromosomes.
46
End with sperm or egg
cells that have the wrong
number of chromosomes.
NONDISJUNCTION
24
24
22
24
22
22
Nondisjunction (Meiosis II)
Start meiosis with one
diploid cell that has 46
chromosomes.
46
End with sperm or egg
cells that have the wrong
number of chromosomes.
23
23
NONDISJUNCTION
23
23
24
22
Nondisjunction: Down Syndrome
Side Note: Maternal Age
• Interestingly, risk of Down Syndrome (and other
trisomies) increases with maternal age.
• Mom’s age | risk of Down | risk of trisomy:
– Age 20
– Age 25
– Age 30
– Age 35
– Age 40
– Age 45
|
|
|
|
|
|
1 in 1667
1 in 1250
1 in 952
1 in 385
1 in 106
1 in 30
|
|
|
|
|
|
http://downsyndrome.about.com/od/diagnosingdownsyndrome/a/Matagechart.htm
1 in 526
1 in 476
1 in 384
1 in 192
1 in 66
1 in 21
Nondisjunction: Klinefelter Syndrome
Deletion/Duplication
Inversion/Translocation
Deletion Example:
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 Example:
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
Translocation Example:
Chronic Mylogenous Leukemia
• 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.”
https://www.cancer.gov/images/cdr/live/CDR533336-750.jpg
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.