Genetics lecture 2 pw_2012

The binomial expansion and probability

A a A a A a A a A a

A AA Aa A AA Aa A AA Aa A AA Aa A AA Aa

a Aa aa a Aa aa a Aa aa a Aa aa a Aa aa

n Here is where the Pascal’s triangle is useful….
(p+q)
0
(p+q) 1
1 1p + 1q
(p+q)
2 1 p2 + 2 p1q1 + 1 q2
(p+q)
3 1 p3 + 3p2q1 + 3p1q2 + 1 q3
(p+q)
4
(p+q) 1 p4 + 4p3q1 + 6p2q2 + 4p1q3 + 1 q4
5
(p+q) 1 p5 + 5p4q1 + 10p3q2 + 10p2q3 + 5 p1q4 + 1 q5
6
(p+q) 1 p6 +6p5q1 + 15p4q2 + 20p3q3 + 15p2q4 + 6p1q5 + 1q6

• If an individual has a dominant phenotype  what is the genotype (AA or Aa)?

- Do a testcross
A A

• Testcross
a Aa Aa
- Take your individual in question and mate
with a homozygous recessive (aa):
a Aa Aa
- Predictions:
1) If the individual is AA
AA x aa  all offspring should have
A a
DOMINANT phenotype
a Aa aa
2) If the individual is Aa
Aa x aa  1/2 should have dom. pheno
a Aa aa
1/2 should have rec. pheno.

 Routinely done to determine the
genotype of an individual

Observed Ratios of Progeny
The Goodness-of-Fit Chi-Square Test

• Observed ratio of progeny may deviate from expected ratios by chance.

We expected a 1:1 ratio, but after counting Yellow and Brown roaches…

There were 22 Brown and 18 Yellow
So… when do we use the Chi-Square Test?
When what comes out is not what we expected!

To see how well observed values FIT the expected values

It indicates the probability that the difference between observed
and expected values is due to chance.


• The hypothesis that chance alone is responsible for any deviation
between observed and expected values is called the null hypothesis .

• Looking at the cats: Black (B) is dominant over Gray (b)

• If we cross 2 heterozygous black (Bb X Bb), we would expect a 3:1 ratio:

B b
• Now we have 50 kittens: 30 black and 20 gray
B BB Bb

b Bb bb


• If we cross 2 heterozygous black (Bb X Bb), we would expect a 3:1 ratio:
• Observed values: 50 kittens: 30 black and 20 gray

• First get the expected values:
B b

Black kittens expected: (3/4) of 50 = 37.5
B BB Bb

b Bb bb Grey kittens expected: (1/4) of 50 = 12.5

S
(observed – expected) 2
Chi-Square value = X2 =
expected
(30 – 37.5) 2 (20 – 12.5) 2
X2 = + X2 = 6
37.5 12.5


X2 = 6
• Then we figure-out the degrees of freedom = n-1
n = the number of ways that things can vary

in the cats‟ case: it‟s “2 phenotypes”

• degrees of freedom = 2-1 = 1

• Now we look at the CHI table and see where “6” is
For a degree of fredom = 1

Table 3.5

The probability of the event due to chance decreases
When value is less than 0.05, chance is not responsible for this!

Solve Problem 35 at the end of chapter 3

Chapter 4
Sex Determination
and
Sex-Linked Characteristics

Chapter 4 Outline
 4.1 Sex Is Determined by a Number of Different
Mechanisms, 74

 4.2 Sex-Linked Characteristics Are Determined by
Genes on the Sex Chromosomes, 81

Sex Determination

• Sexual reproduction is having offspring
that are genetically different from parents

• Meiosis produces haploid gametes

• fertilization produces
diploid zygotes

• Q: What is the fundamental difference
between males and females?
• A: Gamete size, of course!

• However… We define the sex of an individual in reference to its phenotype

Sex Determination

• Usually, females have XX and males XY

• Some rare males have XX sex chromosomes
- With a piece of the Y chrom. (SRY) attached to some
other chromosome…

Sex determination and chromosomal changes

Sex determination
Overview

• Sex determination = Process by which an organism differentiates into one of
two distinguishable sexes (some variations here)

• Some terms related to sex determination:
1) Autosomes – Chromosomes not directly involved in the determination of sex
2) Sex chromosomes – Chromosomes that directly help determine sex
3) Primary sexual differentiation – Formation of the gonads
4) Secondary sexual differentiation – Formation of all other visible traits that are
indicative of a given sex (facial hair, genitalia, etc.)
5) Unisexual – Individuals who have only male OR female reproductive organs
6) Bisexual/hermaphroditic – Individuals who contain both male AND female
sex organs

• Pre-conceived notions from human genetics:
- XX is always female, XY is always male
- Sexual reproducing species have male members and female members
- The bulk of the organism is diploid, gametes are haploid
 Not the case for all species

Major modes of sex determination
Involvement of sex chromosomes
• Discovery of chromosomes involved in sex determination
- Earliest studies were in insects called Protenor
- Female somatic cells = 14 chromosomes,
including 2 X chromosomes
- All female gametes have 7 chromosomes (1 X)

- Male somatic cells = 13 chromosomes, including just 1 X
chromosome
- Half of the male gametes get 7 chromosomes (w/ X) and half have 6 (w/o X)
 Thus, sex in this species is determined by the presence or absence of a
second X chromosome (called the XX/XO mode of sex determination)

- Subsequent studies were done in insects called Lygaeus turicus
- Both females and males have 14 chromosomes
- Both have 12 autosomes
- Females have 2 X chromosomes
- Males have 1 X chromosome and a smaller chromosome called Y
 Thus, sex in this species is determined by the presence of 2 of the same
sex chromosomes or 2 different (heterophilic) sex chromosomes
(called the XX/XY mode of sex determination)


• Discovery of chromosomes involved in sex determination
- In both of the above examples, the male ultimately determines the sex of
offspring because they produce 2 types of gametes (X or no X, X or Y)
- They are called the heterogametic sex
- Females of these species are thus said to be the homogametic sex
• Q: Since the X and Y chromosomes are not homologous, how do they pair-up
and segregate in meiosis?

• A: The X and Y chrom. are homologous in
small
regions called PSEUDOAUTOSOMAL
regions.
In these regions, both X and Y carry the same
genes.

• TIPs: In humans, there are
pseudoautosomal regions at the tips:


- Males are not always the heterogametic sex
- In many species (moths, butterflies, most birds, some fish, reptiles, amphibians),
the female is the heterogametic sex
- Often use the notation ZZ/ZW for these species (ZW – females, ZZ – males)

 Keep in mind that the chromosomes themselves do nothing, it‟s the genes on
the sex chromosomes that are important for sex determination

 In all 3 modes of sex determination just discussed, sex is also INFLUENCED
by genes in the autosomes
- e.g. SOX9 (chr. 17) – Transcription factor involved in male gonad
development

Beyond the sex chromosomes

• Haplodiploidy (bees, ants, wasps)
- Have no sex chromosomes
- Sex is determined by the number of chromosome sets found in the nuclei
- Males develop from unfertilized eggs (HAPLOID)
Females develop from fertilized eggs (DIPLOID)
– Average genetic relatedness between
sisters in this system is 75% (instead of usual 50%)
- Maybe why these species are known for cooperation

• Genic sex determination (some plants and protozoans)
- No obvious differences between chromosomes of males
and females (same number, type)
- Sex is determined by several different genes found on
the autosomes

• Environment controlled sex determination (some reptiles)
- Environment partly or fully controls sex determination
- Example: Temperature at which reptile embryos incubate
determines the sex of the organism

Sex determination in humans

• Sex determination in humans

-individuals with abnormal combinations of sex chromosomes
- XXY and XO  Will they be female or male? Phenotypically normal?

- Results (more later about these syndromes):

- XXY – male characteristics, but with developmental problems
(having an extra X is bad for some reason)
- XO – female characteristics, but with developmental problems
(we need to have 2 sex chromosomes

 The Y chromosome actively tells a human to become a male, even
if that person has 2 X chromosomes

The Role of Sex
Chromosomes

1) You need X!
- At least one X to develop into a human.

2) If you have Y, you‟re a male!

3) Genes affecting fertility are located in both Y and X chrom.
- A female needs at least 2 X‟s to be fertile.

4) Additional X‟s may upset normal development in both
- Additional X‟s produce physical and mental
problems that are proportional to the # of X‟s.

Alterations of sex chromosome number
How does it occur?

• Several conditions exist in which individuals contain an abnormal number
of sex chromosomes
- Individuals look like one of 2 sexes, but have various developmental
abnormalities

• How do individuals obtain an abnormal of sex chromosomes?
- First, a review of meiosis

http://highered.mcgraw-
hill.com/olcweb/cgi/pluginpop.cgi?it=swf::535::
535::/sites/dl/free/0072437316/120074/bio16.swf:
:Unique%20Features%20of%20Meiosis

http://highered.mcgraw-hill.com/sites/0072437316/student_view0/chapter12/animations.html#

How does it occur?

• How do individuals obtain an abnormal # of sex chromosomes?
- Nondisjunction!

The disorders

• Results of nondisjunction in the sex chromosomes:

XX XX XX
meiosis

X X XX XX
fertilization X Y X X Y Y

XX XY XXX

Triplo X
XO

Turner
XXY
XYO

Normal situation Klinefelter Death
syndrome syndrome syndrome

The disorders

• Let's examine the conditions caused by having an abnormal
number of sex chromosomes:

1) Turner syndrome (XO)
- Individuals have only 1 X chromosome (and no Y)
- Most die during embryonic development
- Female genitalia and ducts, but infertile
- Have short stature, underdeveloped feminine traits,
low hair line, broad chest and webbed neck
- Intelligence usually normal

http://www.youtube.com/watch?v=ldjb-FR-PKo&feature=related

The disorders

2) Klinefelter syndrome (XXY)
- Individuals have at least 2 X chromosomes to go along with at least 1 Y chr.
- XXY (most common), XXXY, XXYY, XXXXY, XXXYY

- Have male genitalia and internal ducts, but their
testes are underdeveloped and fail to produce
sperm (they are sterile)

- Are usually very tall, with long arms and legs

- Have several feminine characteristics including
enlarged breasts, rounded hips, and sparse hair

- Can give regular testosterone shots to reduce
feminine characteristics (but still sterile)

Klinefelter syndrome (XXY)

http://www.youtube.com/user/paulawaziry?feature=mhee#
p/c/C038F6E6BFE2738A/27/coGty5bqs4A get correct link

The disorders

3) Triplo X syndrome (XXX) or Poly-X females

- Females that have at least 1 extra X chromosome
- XXX, XXXX, XXXXX
- Highly variable phenotype
- Some women are normal, some have several mental impairment,
some are infertile
- The more X's, the worse the symptoms

4) XYY (superman or supervillain)
- Very controversial condition (was taken out of the book)
- Scientists hypothesized that such individuals may be overly aggressive
and have behavioral problems
- End result: Having an extra Y chromosome (most likely) does not make
you more prone to aggressive behavior
- They did find that men with XYY are taller than average
(usually over 6')

Sex ratios in the human population
Is it 50-50?
• In theory:
- Half of a males gametes should contain an X chr. and half a Y chr.
 Equal numbers of males and females should be conceived and born

• Studies in the 1940s and 60s showed the following:
- Primary sex ratio = ratio of males/females CONCEIVED = ~1.40
- More males are conceived than females. However, male fetuses have a higher
mortality rate (how do we know this)
- Secondary sex ratio = ratio of males/females BORN = ~1.05
- Still more males are born, but not as great a difference as indicated by the
primary ratio

• Any of the above assumptions could be incorrect, leading to these differences
- One idea: Sperm carrying Y has less mass than 1 carrying X. More motile?
- the X sperm is more resistant (survives longer)

The “Y” to become a man

• Y chromosome is extremely small – was thought to be genetically empty
- In recent years, scientists have found several genes located throughout the
Y chromosome (as many as 350)

• Several distinct regions of the Y chromosome have been
identified:
1) Pseudoautosomal regions (PARs)
- Homologous region exists on the X chromosome
- PARs on X and Y contain homologous genes
- Allows the Y chromosome to pair up with the X chr.
during prophase I (allows for crossing over with X)

- Critical for proper segregation of X/Y during meiosis

- Genes found in the PAR region exhibit similar patterns
of inheritance as genes located on the autosomes
- Men are diploid for those genes,
unlike all other genes on X and Y

The Y chromosome
Becoming a man

2) Nonrecombining region of the Y (NRY) – rest of the Y
- This can be divided into several sub-regions:
a) Heterochromatin – Lacks "functional" genes
- Stays hypercondensed in interphase
(when transcription should be occurring)
- Genes, if present, will never be transcribed

b) Euchromatin – Active areas that contain genes that
are constantly being transcribed
- A section of this euchromatin near the PAR on the
p arm contains a critical gene that controls male
development (not found on X)
- Called the Sex determining region of Y (SRY)
- SRY encodes a protein called testis-determining factor (TDF)
- TDF – Binds to DNA and causes it to bend (only known function)
- Present in all male mammals (critical evolutionarily speaking)

The Y chromosome
Becoming a man

Nonrecombining region of the Y (NRY)
- This can be divided into several subregions:

b) Euchromatin
- How do they know the SRY has this function?
- Some human males that have 2 X's and no Y
- SRY was abnormally transferred to one of the X's
- Some human females are XY
- The SRY in the Y chr. has been deleted
- Transferring just the SRY gene into mouse
embryos that are XX causes all embryos to
develop into males

- Euchromatin contains many other genes
- Some have homologs on X and appear to play no direct role in sex
determination (expressed in many tissues)
- Others are believed to play a role in male fertility
- Mutations in these genes often cause male sterility

Extensions of Mendel
Sex-linked genes

• See different inheritance patterns if genes are located on the X or Y chr.
- Females XX, males XY
- If a gene is on the X chromosome, males can only be hemizygous

- Example: Dominant allele of a gene causes fruit flies to have red eyes (E) and a
recessive form (e) causes them to have white eyes.
- Imagine that we cross a pure bred red-eyed female and a white-eyed male

Gene not located on Gene located on
a sex chromosome the X chromosome

E E female XE XE

e Ee Ee Xe XEXe XEXe
male
e Ee Ee Y XEY XEY

All F1 (male and female) All F1 (male and female)
are heterozygous and have have red eyes
red eyes

Sex-linked genes

• How do we know which genes are on the sex (X and Y) chromosomes?
- Let's look at the F2 generation
Gene not located on Gene located on
a sex chromosome the X chromosome

E e female XE Xe

E EE Ee XE XEXE XEXe
male
e Ee ee Y XEY XeY

See a 3:1 ratio of red to white 100% of females have red eyes
in the F2 – no pattern for males 50% of males have red, 50% white
and females

Some X-linked human disorders
Color blindness, muscular dystrophy, and hemophilia (all are recessive)

X-linked Color Blindness in Humans

• The color blindness gene is recessive (b). The normal gene is dominant (B).
Gene located on
Q: What is the genotype of normal females and males?
the X chromosome
Normal Color blind
XB XB Xb Xb
XB Xb Xb Y XB Xb
XB Y
XB XBXB XBXb
Q: If you have a boy that is color blind,
and parents who are normal, what is Y XBY XbY
the genotype of the mother?
She is a hererozygous / carrier

X-linked Color Blindness in Humans

Q: Betty has normal vision, but her mother is color blind. Bill is color blind. If Bill and
Betty have a child, what is the probability that the child will be color blind?
A: 1) Is it sex-linked? Yes
Gene located on
2) Draw possible genotypes:
the X chromosome
Normal Color blind
XB XB Xb Xb Xb
XB
XB Xb Xb Y
XB Y
Xb XBXb XbXb

3) Betty (with normal vision) is a carrier
(mom is color blind) Y XBY XbY

4) Bill is color blind

5) Probability for child
to be color blind:
(1/4)+(1/4)=1/2 or 50%

Dosage compensation
Inactivating X

• Since human females have 2 X chr. and males have 1, females should have twice
the amount of proteins that are encoded by genes located on the X chr.
- Furthermore, women that are XXX should have 3 times the amount
- NOT THE CASE!

• Early in embryonic development (~ 8 cell stage), each cell in the female
embryo will randomly inactivate 1 of its X chromosomes
- Each cell derived from those original 8 will have the same inactivation pattern
- Example: If X chr. 1 is inactivated in cell #4, all cells derived from #4 will have
X chr. 1 inactivated

• The inactivated X chr. becomes highly condensed and is observed
as a dark spot at the edge of the nucleus (during interphase)
- Called a Barr body

• So, why is having XXY or XXX harmful?
- Possible that having an extra X is bad early in development
- Possible that part of the X is still active (near PARs)

Dosage compensation
Inactivating X

• How does X inactivation occur?
- A region of the X chromosome called the X-inactivation center (XIC) is
required for X chr. inactivation
- XIC contains a gene that is transcribed – produces a transcript called
X-inactive specific transcript (Xist)
- Xist is only produced from the X chromosome that will be inactivated
- Xist is not produced from the active X chromosome
- Xist is never translated into protein
- Xist RNA is thought to form a coat around the X chr. and somehow
prevents acetylation, induces methylation, ......

• What don't we know?
- In cases of XXY or XXX, how do cells count how many X's should be inactivated?
- What prevents the production of Xist from the "good" X chromosome?
- How do progeny cells keep the same pattern of X inactivation? Does it stick with
the chromosomes during replication and mitosis?

Chapter 5 Outline
 5.1 Additional Factors at a Single Locus Can Affect the Results of
Genetic Crosses, 100

 5.2 Gene Interaction Takes Place When Genes at Multiple Loci
Determine a Single Phenotype, 106

 5.3 Sex Influences the Inheritance and Expression of Genes in a
Variety of Ways, 115

 5.4 Anticipation Is the Stronger or Earlier Expression of Traits in
Succeeding Generations, 122

 5.5 The Expression of a Genotype May Be Affected by
Environmental Effects, 123

Benjamin A. Pierce

GENETICS
A Conceptual Approach
 FOURTH EDITION

CHAPTER 5
Extensions and Modifications
of Basic Principles
© 2012 W. H. Freeman and Company

5.1 Additional Factors at a Single Locus
Can Affect the Results of Genetic Crosses

 Multiple alleles: For a given locus, more than two
alleles are present within a group of individuals.
 Fig. 5.5
 ABO blood group
 Fig. 5.6

5.1 Additional Factors at a Single Locus Can
Affect the Results of Genetic Crosses

 Genes at the same locus - two versions of the
same gene; each version of the same gene is
defined as allele.
 Fig. 5.2
 Incomplete dominance
 Codominance
 Table 5.1

Incomplete dominance and codominance

X

• Incomplete dominance (more like the “blending”)
- Neither allele is dominant
- Heterozygotes look like an intermediate between homozygotes
- They have a different phenotype than either homozygote
- Example: Red snapdragons x white snapdragons  Pink snapdragons
- RR x WW  RW

Important: It affects the phenotype, but not the way in which genes are inherited.

Incomplete dominance and codominance

• Codominance
- Both alleles are dominant (neither backs down)
- Heterozygotes look like a combination of homozygotes
- They possess both phenotypes of the homozygotes
- Examples: Sickle-cell disease and ABO blood type

Type A Type B Type AB Type O
(IAIA or IAi) (IBIB
or IBi) (IAIB) (ii)


• Dependency of Type of Dominance on Level of Pheno Observed
- Both alleles are expressed (neither backs down)
- Case of cystic fibrosis
- Caucasian disorder
- usually recessive disease
- production of thick, sticky mucus: clogs pancreas ducts;
and airways
- Gene on long arm of Chr.7
- Cystic Fibrosis Transmembrane conductance Regulator
- CFTR
- regulates movement of Cl- ions

If heterozygous, there is codominance at
molecular level;
However, normal Cl- transport;
Physiological level: mutated allele appears
To be recessive.

DOMINANCE = ALLELIC INTERACTION  GENES AT THE
SAME LOCUS
http://www.youtube.com/watch?v=r7HP0whUMbE&feature=rel

Lethal alleles
• Lethal alleles – Their presence results in death of the organism
- Many are embryonic lethal – individual is never born

• Most lethal alleles are recessive, but some are dominant

1) Recessive lethal alleles (e.g. Tay Sachs – kills before age 3)
- Two copies of allele needed for lethality
- AA/Aa  Normal aaLethal F f
http://www.youtube.com/watch?v=SeoPF74QSms

- Example: Mating two green corn plants yields F FF Ff
2/3 green progeny and 1/3 white progeny. How?
- Good example of AA and Aa having diff. phenotypes f Ff ff

2) Dominant lethal alleles (e.g. Huntington)
- Only one copy needed for lethality http://www.youtube.com/watch?v=MRZoM5L5dak
- AA/Aa  Lethal aa  Normal (Dominant isn't always better!!)
- Can only pass on to kids if reproduce before it kills
- Example: Huntington's Disease
- Doesn't kill until age >30
- If it killed at age 2, could an Aa person pass it on?

Lethal alleles

• Lethal alleles – Their presence results in death of the organism
- Many are embryonic lethal – individual is never born

• Most lethal alleles are recessive, but some are dominant

1) Recessive lethal alleles (e.g. Tay Sachs – usually kills before age 3)
- Two copies of allele needed for lethality
- AA/Aa  Normal aaLethal
http://www.youtube.com/watch?v=SeoPF74QSms

- Example: Corn: Mating two green corn plants yields
2/3 green progeny and 1/3 white progeny. How?
- Good example of AA and Aa having diff. phenotypes
(also example of incomplete dominance)
F f

F FF Ff

f Ff ff

Lethal alleles

• Lethal alleles

2) Dominant lethal alleles (e.g. Huntington)
- Only one copy needed for lethality
http://www.youtube.com/watch?v=MRZoM5L5dak

AA/Aa  Lethal
aa  Normal (Dominant isn't always better!!)

- Can only pass on to kids if reproduce before it kills
- Huntington's Disease doesn't kill until age >30
- If it killed at age 2, could an aa person pass it on?

A a

A AA Aa

a Aa aa

5.1 Additional Factors at a Single Locus
Can Affect the Results of Genetic Crosses

 Penetrance : the percentage of individuals having a
particular genotype that express the expected
phenotype.

 Expressivity: The degree to which a characteristic is
expressed.

Penetrance vs. expressivity

• Two individuals with the same genotype can have different phenotypes
- More than genotype affects phenotype
- Nature vs. nurture

• Penetrance vs. expressivity

- Penetrance = Frequency, under a given environmental condition, with which
a specific phenotype is observed by individuals with a specific genotype

- If only 10% of individuals have expected phenotype  low penetrance
- Phenotype is affected by other things

- If 95% of individuals have expected phenotype  high penetrance
- Genotype has dominant effect on phenotype

EX: 42 people have the allele, but only 38 express the gene.

Penetrance = 38/42 = 0.9 = 90%


• Two individuals with the same genotype can have different phenotypes
- More than genotype affects phenotype
- Nature vs. nurture

- Expressivity = The range of different phenotypes observed for a given genotype
- Example: Polydactyly in humans
- Child 1: Only a little slab of skin (low expressivity)
- Child 2: Fully functional extra digit(s) (high expressivity)

 THE PHENOTYPE IS SHOWING = with penetrance
HOW IS IT SHOWING? = expressivity

Concept Check 1
Assume that long fingers are inherited as a recessive
trait with 80% penetrance. Two people heterozygous
for long fingers mate. What is the probability that
their first child will have long fingers?

Concept Check 1
Assume that long fingers are inherited as a recessive
trait with 80% penetrance. Two people heterozygous
for long fingers mate. What is the probability that
their first child will have long fingers?

¼ X 80% = 20%

Concept Check 2

 A cross between two green corn plants yields 2/3
progeny that are green and 1/3 progeny that are white.
 What is the genotype of the green progeny and the white
progeny?

Concept Check 2
 A cross between two green corn plants yields 2/3
progeny that are green and 1/3 progeny that are white.
 What is the genotype of the green progeny and the white
progeny?

White genotype: GG;
Green genotype: Gg
gg: lethal allele causing death in homozygous.

Concept Check 3
What blood types are possible among the children of a
cross between a man who is blood-type A and a
woman of blood-type B?

Concept Check 3
What blood types are possible among the children of a
cross between a man who is blood-type A and a
woman of blood-type B?
Could be: A type with a genotype of IAIA
and IAi;
 Could be B type with a genotype of IBIB or IBi
 Could be AB type with a genotype of IAIB
 Could also be a O type with a genotype of ii

5.2 Gene Interaction Takes Place When
Genes At Multiple Loci Determine a Single
Phenotype

• Gene interaction: Effects of genes at one
locus depend on the presence of genes at
other loci.
– Gene interaction that produces novel
phenotypes.
• Fig. 5.7
– Gene interaction with epistasis
• Epistasis: one gene masks the effect of another
gene.

Polygenic inheritance - Epistasis

• A gene is not a hermit!!!

• It will often interact with others.


• Epistasis  Specific case of polygenic inheritance in which one gene interferes
with the expression of a totally different gene

- Gene A blocks the effect of gene B on the phenotype
- Example: Gene A leads to hair production, Gene B leads to hair color
- What would happen if gene A were defective?

• Different types of epistasis
1) Recessive epistasis
- Two recessive alleles of gene “a” blocks gene B
- If have "aa", doesn't matter what gene B is.

2) Dominant epistasis
- One dominant allele of gene A blocks gene B
- If have "A_", doesn't matter what gene B is.


• Epistasis  Specific case of polygenic inheritance in which one gene interferes
with the expression of a totally different gene
- Gene A blocks the effect of gene B on the phenotype
- Example: Gene A leads to hair production, Gene B leads to hair color
- What would happen if gene A were defective?

EPISTATIC
(cont.)
3) Duplicate recessive epistasis
- Two genes can block each other
("aa" can block B and "bb" can block A)

4) Duplicate dominant epistasis
("A_" can block B and "B_" can block A)


• Epistasis examples
- Set-up
- Genes A and B contribute to color an animal (black, brown, albino)
- Defining albino as a lack of color (yellow labrador example)

- Mating AaBb x AaBb A a B b

- Possible genotypes A AA Aa B BB Bb
A_B_ 9/16
aaB_ 3/16
a Aa aa b Bb bb
A_bb 3/16
aabb 1/16

- Phenotypic ratios if epistasis
1) Recessive epistasis (assume aa is epistatic to gene B)
A_B_ 9/16  Black If have "aa", gene B doesn't matter
A_bb 3/16  Brown  Get 9:3:4 ratio for this cross
aaB_ 3/16  Albino
aabb 1/16  Albino

DON'T
MEMORIZE
NUMBERS!!
• Epistasis examples
- Phenotypic ratios if epistasis
2) Dominant epistasis (assume A_ is epistatic to gene B)
A_B_ 9/16  Albino
A_bb 3/16  Albino If have "A_", gene B doesn't matter
aaB_ 3/16  Black  Get 12:3:1 ratio for this cross
aabb 1/16  Brown

3) Duplicate recessive epistasis (aa and bb can block the other)
A_B_ 9/16  Black
A_bb 3/16  Albino If have either aa or bb, the other gene doesn't
aaB_ 3/16  Albino matter
aabb 1/16  Albino  Get 9:7 ratio for this cross

4) Duplicate domiant epistasis (A_ and B_can block the other)
A_B_ 9/16  Albino
A_bb 3/16  Albino If have either A_ or B_, the other gene doesn't
aaB_ 3/16  Albino matter
aabb 1/16  Black  Get 15:1 ratio for this cross

Concept Check 4
A number of all-white cats are crossed and they
produced the following types of progeny: 12/16 all-
white; 3/16 black; and 1/16 gray. What is the
genotype of the black progeny?
a. Bb
b. BbAa A_B_ 9/16 
c. B_A_ Albino
d. B_aa A_bb 3/16 
Albino
aaB_ 3/16  Black
aabb 1/16  Brown

5.2 Gene Interaction Takes Place When
Genes At Multiple Loci Determine a Single
Phenotype

• Complementation: Determine whether mutations
are at the same locus or at different loci.

Complementation analysis
Determining how many genes affect a given trait

• Complementation analysis – Experiment used to determine
how many genes affect a given trait

• If you mate 2 mutant flies together, you would expect to see the following:
1) If the 2 flies have mutations in different genes (non-allelic)
fly 1 fly 2
X X
X
X X
A B A B
wingless wingless
Each of the offspring get
1 good copy of gene A and
1 good copy of gene B All F1 offspring
X
 The 2 genes complement
each other X
A B
WINGS!!

Complementation analysis
Determining how many genes affect a given trait

• If you mate 2 mutant flies together, you would expect to see the following:
2) If the 2 flies have mutations in the same gene (allelic)
fly 1 fly 3
X X
X
X X
A B A B
wingless wingless

Each of the offspring get
All F1 offspring
2 bad copies of A
X
 NO complementation!! X
A B
All flies that fail to complement wingless
one another have mutations in
the same gene

Sex-influenced and sex-limited traits

5.3 Influences the inheritance and expression of genes in a variety of ways.

Some traits are observed largely in one sex over another despite being
controlled by an autosomal gene

- If MOSTLY in one sex = Sex-influenced (higher penetrance in one sex)
if ONLY in one sex = Sex-limited (no penetrance in the other sex)

- Usually due to differences in sex hormone production

5.3 Sex Influences the Inheritance and
Expression of Genes in a Variety of Ways.

 Genetic maternal effect
 Genomic imprinting : differential expression of
genetic material depending on whether it is inherited
from the male or female parent.
 Epigenetics: Phenomena due to alterations to DNA
that do not include changes in the base sequence; often
affect the way in which the DNA sequences are
expressed.


 How the sex of an individual can influence the
expression of genes on:
1) autosomal chromosomes
2) characteristics determined by genes in the
cytoplasm
3) characteristics for which maternal genotype
determines phenotype of offspring
4) expression of autosomal genes and how it is
affected by the sex of the parent from whom the
gene was inherited.


• Example: Male-pattern baldness
- Controlled by an autosomal enzyme that converts testosterone to
DHT (Dihydrotestosterone)
- DHT alters gene expression in the scalp  Baldness
- Females have little testosterone
- May make enzyme, but lack of testosterone makes it quiet.

Mitochondrial inheritance and maternal effect

• Mitochondrial genome is very different from the nuclear genome
- All genes on a single circular chromosome
- Each mitochondrion has several copies, each cell has
1000s of mitochondria
 High copy number
- Only passed from mom  offspring
- Most genes encode either tRNAs or cellular respiration proteins

• Mitochondrial genome is not diploid, but not quite haploid
- Every cell has a mixture of mitochondrial genomes
- Lots of variability due to high copy number
 Mitochondrial inheritance is very complicated!!

• Mechanisms for mtDNA inheritance include

(A) dilution: an egg has 100,000 to 1,000,000 mtDNA molecules, versus
100 to 1000 on a sperm,
(B) Degradation of sperm mtDNA in the fertilized egg;
(C) Failure of sperm mtDNA to enter the egg.

Whatever the mechanism, this pattern of mtDNA inheritance is found in most
animals, most plants and in fungi as well.


• Cytoplasmic Inheritance: chloroplasts/ mitochondria
- mtDNA is inherited from the mother (maternally inherited).
- mitochondrial diseases are inherited from the mother.

Ex: Leber Hereditary Optic Neuropathy (LHON)
Rapid loss of vision in both eyes resulting from death of cells in optic
nerve. Onset ~ 20 – 24 years
http://www.youtube.com/watch?v=RQLdKEaExRA&feature=related

Mitochondrial inheritance and maternal effect

• Genetic maternal effect
- Proteins in the mom's egg play a major role in embryonic development

- Mom's genotype solely determines phenotype of her offspring
- No role of dad's or offspring's DNA

- Mutate mom's DNA  mutant egg protein  mutant develop.


• Some factors that affect penetrance/expressivity of a gene

3) Epigenetics
- Methylation can shut down gene expression
without altering genotype

- Imprinting is good example, where the information in certain genes
is active only when it passes to a child through the sperm or the egg.
- The system of being „stamped‟ according to the paternal or maternal origin
of a gene copy

 All affect gene expression (transcription levels)
while having no effect on DNA sequence


- Imprinting

- Males and females do not contribute the same genetic material to
the offspring

- Autosomal genes – long assumed to have equal effects on gene
expression

- However, the expression of some genes is significantly affected
by the parental origins

- There are several human disorders associated with imprinting:

EX) Prader-Willi and Angelman Syndromes


- Imprinting
EX: 1) Prader-Willi Syndrome: child is missing a small region on the
long arm of chrom. 15 that was inherited from the father.
• Small hands and feet
• Short stature
• Poor sexual development
• Mental retardation
• Frequently obese
http://www.youtube.com/user/paulawaziry?feature=mhee#p/c/C038F6E6BFE2738A/5/X-QAIO3t41U

EX: 2) Angelman Syndrome:
Same region of chrom. 15 is missing, but now from the mother’s
chrom.
• Frequent laughter
• Uncontrolled muscle movement
• Large mouth
• Unusual seizures

Genetics lecture 2 pw_2012

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