Download 11/18

Today: Imprinting and Linkage
Exam #3 T 12/2 in class
Final Sat. 12/6 from 9am – 12noon in BIO 301
Genotype
Phenotype
Genes code for
proteins (or RNA).
These gene
products give rise
to traits…
It is rarely this
simple.
Lamarck was right? Sort of…
Epigenetics:
http://www.pbs.org/wgbh/nova/sciencenow/3411/02.html
Image from: http://www.sparknotes.com/biology/evolution/lamarck/section2.rhtml
Genomic Imprinting
• Genomic imprinting is a phenomenon in which
expression of a gene depends on whether it is
inherited from the male or the female parent
• Imprinted genes follow a non-Mendelian pattern
of inheritance
– Depending on how the genes are “marked”, the
offspring expresses either the maternallyinherited or the paternally-inherited allele
**Not both
A hypothetical example of imprinting
a
B*
A=curly hair
A*
a=straight hair
B=beady eyes
b
A*a
bB*
similar to Fig 7.10
a
B* A*
b
A*a
bB*
b=normal
*=methylation
A*a
bB
Aa
bB*
A* in males
B* in females
A*b, A*B,
ab, aB
Ab, AB*,
ab, aB*
Imprinting and DNA Methylation
• Genomic imprinting must involve a marking
process
• At the molecular level, the imprinting is
known to involve differentially methylated
regions
– They are methylated either in the oocyte or
sperm
• Not both
• For most genes, methylation results in
inhibition of gene expression
–However, this is not always the case
Changes in methylation during gamete
development alter the imprint
Haploid female gametes transmit
an unmethylated gene
Fig 7.11
Haploid male gametes transmit
a methylated gene
Thus genomic imprinting is permanent in the
somatic cells of an animal
– However, the marking of alleles can be altered from generation
to generation
To date, imprinting has been identified in dozens of
mammalian genes
Tbl 7.2
Tbl 7.2
Imprinting plays a role in the inheritance of
some human diseases: Prader-Willi syndrome
(PWS) and Angelman syndrome (AS)
–PWS is characterized by: reduced motor function,
obesity, mental deficiencies
–AS is characterized by: hyperactivity, unusual seizures,
repetitive muscle movements, mental deficiencies
Usually, PWS and AS involve a small deletion
in chromosome 15
–If it is inherited from the mother, it leads to AS
–If it is inherited from the father, it leads to PWS
• AS results from the lack of expression of
UBE3A (encodes a protein called EA-6P that transfers small
ubiquitin molecules to certain proteins to target their degradation)
– The gene is paternally imprinted (silenced)
• PWS results (most likely) from the lack of
expression of SNRNP (encodes a small nuclear
ribonucleoprotein that controls gene splicing necessary for the
synthesis of critical proteins in the brain)
– The gene is maternally imprinted (silenced)
The deletion is
the same in
males and
females, but the
expression is
different
depending on
who you
received the
normal version
from.
Fig 7.12
The relationship between genes
and traits is often complex
Complexities include:
• Complex relationships between alleles
The relationship between genes
and traits is often complex
Complexities include:
• Multiple genes controlling one trait
Two genes control
coat color in mice
Fig 4.21
Variation in Peas
Fig 3.2
Fig 2.8
Inheritance of 2 independent
genes
Approximate position of seed color and shape genes
in peas
Y
y
Gene for seed color
r
Chrom. 1/7
R
Chrom. 7/7
Gene for
seed shape
There must be a better way…
Fig 2.9
Inheritance
can be
predicted by
probability
Section 2.2, pg 30-32
Sum rule
• The probability that one of two or more mutually
exclusive events will occur is the sum of their
respective probabilities
• Consider the following example in mice
• Gene affecting the ears • Gene affecting the tail
– De = Normal allele
– de = Droopy ears
– Ct = Normal allele
– ct = Crinkly tail
• If two heterozygous (Dede Ctct) mice are crossed
• Then the predicted ratio of offspring is
–
–
–
–
9 with normal ears and normal tails
3 with normal ears and crinkly tails
3 with droopy ears and normal tails
1 with droopy ears and crinkly tail
• These four phenotypes are mutually exclusive
– A mouse with droopy ears and a normal tail cannot have
normal ears and a crinkly tail
• Question
– What is the probability that an offspring of the above
cross will have normal ears and a normal tail or have
droopy ears and a crinkly tail?
• Applying the sum rule
– Step 1: Calculate the individual probabilities
P(normal ears and a normal tail) =9 (9 + 3 + 3 + 1) = 9/16
P(droopy ears and crinkly tail) =1 (9 + 3 + 3 + 1) = 1/16
– Step 2: Add the individual probabilities
9/16 + 1/16 = 10/16
• 10/16 can be converted to 0.625
– Therefore 62.5% of the offspring are predicted to have
normal ears and a normal tail or droopy ears and a
crinkly tail
Product rule
• The probability that two or more independent
events will occur is equal to the product of
their respective probabilities
• Note
– Independent events are those in which the
occurrence of one does not affect the probability of
another
• Consider the disease congenital analgesia
– Recessive trait in humans
– Affected individuals can distinguish between sensations
• However, extreme sensations are not perceived as painful
– Two alleles
• P = Normal allele
• p = Congenital analgesia
• Question
– Two heterozygous individuals plan to start a family
– What is the probability that the couple’s first three children will all have
congenital analgesia?
• Applying the product rule
– Step 1: Calculate the individual probabilities
• This can be obtained via a Punnett square
P(congenital analgesia) = 1/4
– Step 2: Multiply the individual probabilities
1/4 X 1/4 X 1/4 = 1/64
• 1/64 can be converted to 0.016
– Therefore 1.6% of the time, the first three offspring of a
heterozygous couple, will all have congenital analgesia
Different
genes are not
always
independent
Crossingover
Meiosis I
(Ind. Assort.)
Meiosis II
4 Haploid cells, each unique
Fig 5.1
The haploid cells contain
the same combination of
alleles as the original
chromosomes
The arrangement of linked
alleles has not been altered
Fig 5.1
These haploid cells contain a
combination of alleles NOT
found in the original
chromosomes
These are
termed
parental or
nonrecombinant
cells
This new combination of
alleles is a result of
genetic recombination
These are termed
recombinant cells
Linked alleles tend to be inherited together
Recombinants are produced by crossing over
Crossing over produces new allelic combinations
Only 2 chromosomes cross-over, and so the
maximum number of recombinants that can be
produced is 50%.
For linked
genes,
recombinant
frequencies are
less than 50
percent
Homologous
pair of chromosomes
Does this show recombination?
D/d
M1/M2
d/d
M1/M2
D/d
M1/M2
d/d
M2/M2
D/d
M2/M2
d/d
M2/M2
Does this show recombination?
D/d
M1/M2
d/d
M1/M2
D/d
M1/M2
d/d
M2/M2
D/d
M2/M2
d/d
M2/M2
Longer regions
have more
crossovers and
thus higher
recombinant
frequencies
Some crosses
do not give
the expected
results
=25%
42% 41%
9%
8%
These two genes are on the same chromosome
By comparing recombination frequencies, a linkage
map can be constructed
By comparing recombination frequencies, a linkage
map can be constructed
= 17 m.u.
Linkage map of
Drosophila
chromosome 2:
This type of map, with
mapping units more
than 50, can only be
put together by
making comparisons
of linked genes.
The probability of crossing over can be used to
determine the spatial relationship of different genes
What is the relationship between
these 3 genes? What order and
how far apart?
similar to Fig 5.3,
also see Fig 5.9,
and pg 115-117