Bridges and Triploids

1
Bridges and Triploids
White XwXwY
red XWY
2
Triploidy
Species that are triploid, reproduce asexually
(plant species) What are the consequences of
triploidy during mitosis and meiosis?
Diploid
Haploid
Triploid
Mitosis
3
Triploidy
Species that are triploid, reproduce asexually
(plant species) What are the consequences of
triploidy during mitosis and meiosis?
Diploid
Haploid
Triploid
Mitosis
4
Meiosis and triploids
MeiosisI
This is for one chromosome. If there are n
chromosomes in an organism, then balanced gametes
(equal copies of all chromosomes) are very rare.
5
Meiosis and triploids
MeiosisI
This is for one chromosome. If there are n
chromosomes in an organism, then balanced gametes
(equal copies of all chromosomes) is very rare.
6
Seedless watermelons
Triploidy is useful in agriculture. Biological
control Cross a tetraploid watermelon with a
diploid watermelon
7
And triploid toads
Triploid toads Nature Genetics 30, 325 - 328
(2002) Tetraploid green toads reproduce through
diploid eggs and sperm cells. A new taxon was
discovered at an isolated site in the Karakoram
mountain range. Every wild toad caught from eight
localities was triploid Did not find a single
diploid or tetraploid Batura toad. Both males and
females were found
3N female 3N male N elimination N
elimination 2N 2N 2N N
N 3N
8
Sex in organisms
Sex chromosomes and sex linkage In Drosophila,
it is the number of X's that determine sex while
in mammals it is the presence or absence of a Y
chromosome that determines sex. Homogametic
sex- Producing gametes that contain one type of
chromosome (females in mammals and insects, males
in birds and reptiles) Heterogametic sex-
Producing gametes that contain two types of
chromosomes (males in mammals and insects,
females in birds and reptiles)
Bridges could tell genotype by where the sex
chromosome went and therefore established that
chromosomes carried genes
9
Non-sex chromosomes are called autosomes Humans
have 22 autosomes, Drosophila has 3 Homogametic
sex- XX- females in humans males in
birds Heterogametic sex- XY- males in
humans Hemizygous gene present in one copy in
a diploid organism Human males are
hemizygous for genes on the X-chromosome
10
Sex linked
Described below is an actual case history of the
use of pedigree analysis
After the death of a wealthy individual (II3), a
man claiming to be his son (III3) filed a
paternity suit and claimed the inheritance. The
deceased had only two living nephews (III1 and
III2 who were sons of his brothers (II1 and
II2). In determining whether the man was
actually the son and had the rights to the
inheritance which of the following markers would
be most useful Autosomal X-linked Y-linked

11
Surname project
Y
Y
Y
Y
All males in this pedigree will have the SAME
Y-chromosome!!!
12
Mammalian X-chromosome inactivation(epigenetics)
Mammalian males and females have one and two X
chromosomes respectively. One would expect that
X-linked genes should produce twice as much gene
product in females compared to males. Yet when
one measures gene product from X-linked genes in
males and females they are equivalent. This
phenomenon, known as dosage compensation, means
that the activity of X-linked genes is either
down regulated in females or up regulated in
males. The former proves to be the case X
chromosome inactivation in females is the
mechanism behind dosage compensation. In females,
one of the X chromosomes in each cell is
inactivated. This is observed cytologically. One
of the X-chromosomes in females appears highly
condensed. This inactivated chromosome is called
a Barr-body. In Drosophila the genes on the
single male X chromosome is up-regulated 2-fold
13
X-inactivation
The inactivation of one of the two X-chromosomes
means that males and females each have one active
X chromosome per cell. X-chromosome inactivation
is random. For a given cell in the developing
organism there is an equal probability of the
female or the male derived X chromosome being
inactivated.
The embryo is a mosaic! Once the decision is made
in early development, then it is stably
inherited. Patches of cells have the male X ON
and patches of cells have the female X ON This is
a Developmental rule that overlays on top of
Mendellian rules!
14
Barr bodies
XXX individuals have 2 Barr Bodies leaving one
active X XXXX individuals have 3 Barr Bodies
leaving one active X XXY individual have one
Barr Body leaving one active X (Klinefelter's
syndrome) X0 individuals have no Barr Bodies
leaving one active X (Turner's syndrome) Given
X-chromosome inactivation functions normally why
are they phenotypically abnormal? The answer to
this is not completely understood, but part of
the explanation for the abnormal phenotypes is
that the entire X is not inactivated during
Barr-Body formation. Consequently an X0
individual is not genetically equivalent to an XX
individual.
15
Mendelian genetics in Humans Autosomal and
Sex-linked patterns of inheritance
Obviously examining inheritance patterns in
humans is much more difficult than in Drosophila
because defined crosses cannot be constructed. In
addition humans produce at most a few offspring
rather than the hundreds produced in experimental
genetic organisms such as Drosophila It is
important to study mendellian inheritance in
humans because of the practical relevance and
availability of sophisticated phenotypic
analyses. Therefore the basic methods of human
genetics are observational rather than
experimental and require the analysis of matings
that have already taken place rather than the
design and execution of crosses to directly test
a hypothesis To understand inheritance patterns
in human genetics you often follow a trait for
several generations to infer its mode of
inheritance. For this purpose the geneticist
constructs family trees or pedigrees. Pedigrees
trace the inheritance pattern of a particular
trait through many generations. Pedigrees enable
geneticists to determine whether a familial trait
is genetically determined and its mode of
inheritance (dominant/recessive,
autosomal/sex-linked)
16
Pedigree symbols
Male
Female
Sex Unknown
5
Affected individual
Deceased
Number of individuals
Spontaneous abortion
Termination of pregnancy
17
Pedigree symbols
relationship line
Sibship line
line of descent
individuals lines
consanguinity
Monozygotic
Dizygotic
18
Characteristics of an autosomal recesssive trait

• Patterns in pedigrees of Autosomal recessive
  traits
• There are several features in a pedigree that
  suggest a recessive pattern of inheritance
• Rare traits, the pedigree usually involves mating
  between two unaffected heterozygotes with the
  production of one or more homozygous offspring.
• 2. The probability of an affected child from a
  mating of two heterozygotes is 25
• 3. Two affected individuals usually produce
  offspring all of whom are affected
• 4. Males and females are at equal risk, since the
  trait is autosomal
• 5. In pedigrees involving rare traits,
  consanguinity is often involved.

In the pedigree shown below, an autosomal
recessive inheritance pattern is observed
19
Characteristics of an autosomal dominant trait
1. Every affected individual should have at least
one affected parent. 2. An affected individual
has a 50 chance of transmitting the trait 3.
Males and females should be affected with equal
frequency 4. Two affected individuals may have
unaffected children
20
The following pedigree outlines the typical
inheritance pattern found in red-green
color-blindness.
Does this fit an autosomal recessive or autosomal
dominant pattern of inheritance?
21
Characteristics of a sex-linked trait
Hemizygous males and homozygous females are
affected Phenotypic expression is much more
common in males than in females, and in the case
of rare alleles, males are almost exclusively
affected Affected males transmit the gene to all
daughters but not to any sons Daughters of
affected males will usually be heterozygous and
therefore unaffected. Sons of heterozygous
females have a 50 chance of receiving the
recessive gene.
22
(No Transcript)
23
Dominance relationships
24
What is the biochemical explanation for dominance?
The genetic definition of dominance is when an
allele expresses its phenotype in the
heterozygous condition. By saying A is dominant
over a, we are saying AA and Aa have the same
phenotype. Conversely the genetic definition of
recessive is when allele does not express its
phenotype in the heterozygous condition. For
example a gene responsible for height in the pea
plant has a dominant allele, T. T/T 6ft T/t
6ft t/t2ft By definition T is dominant to t.
And t is recessive to T. Now if the short
phenotype is observed in the heterozygote, then t
is dominant and short is dominant to tall.
25
Genes make enzymes
Many, but not all genes, are responsible for the
production of specific enzymes. Remember
enzymes catalyze biochemical reactions.
Substrate ---------gt product EnzymeA
GeneA Wild-type phenotype observed
most of the time in nature
26
Incomplete dominance-
Although straightforward dominance/recessive
relationships are the rule, there are a number of
variations on this pattern of inheritance. One
of these variations is called Incomplete
dominance Incomplete dominance is the occurrence
of an intermediate phenotype in the heterozygote.
The heterozygote exhibits a phenotype
intermediate between the two homozygotes A good
example of this is in four o'clock
plants How are these results explained
genetically? How do we relate genotype to
phenotype By applying Mendel's laws can you
relate the phenotypic classes to the genotypic
classes?
27
The following explanation readily explains the
phenotypic outcome P Pure white x Pure
red F1 All Pink F2 1/4Red 1/2Pink 1/4White
Do not use C and c to denote the two alleles-
Use C1 and C2 In practice incomplete
dominance can lie anywhere on the phenotypic
scale The phenotype of the heterozygous
individual is the key towards determining
whether an allele behaves as a recessive,
dominant, or incomplete dominance If there is
incomplete dominance, then Phenotype ratio
Genotype ratio
28
The classic example of this is the colors of
carnations. R1 R2 R1 R1R1 R1R2 R2 R1R2
R2R2 R1 is the allele for red pigment. R2 is
the allele for no pigment. Thus, R1R1 offspring
make a lot of red pigment and appear red. R2R2
offspring make no red pigment and appear white.
R1R2 and R2R1 offspring make a little bit of red
pigment and therefore appear pink. Often in
biological systems, substrate is limiting leading
to incomplete dominance phenotypes.
29
Co-dominance
The biochemical basis of co-dominance is
understood for the blood groups M and N The
surface of a red blood cell carries molecules
known as antigens. More than 20 different blood
group systems are recognized. the best known are
the ABO system and the Rh system. The MN blood
group system is of little medical importance.
In this system there are two antigens, M and N.
The L gene in humans codes for a protein
present on the surface of the red blood cells.
There exist two allelic forms of this gene
These two alleles represent two different
forms of the protein. So with respect to the
red blood cells, the genotype and phenotype
relationships are as follows
30
Both proteins are being expressed in the
heterozygote.
We are used to phenotypes as flower color,
height, hair length, shape etc. The blood group
phenotype is at a much finer level- that of the
cell and is harder to observe. Remember
the phenotype chosen is what the geneticists
happens to notice. In this respect it can be
somewhat subjective and depend on how observant
the geneticists happens to be.
31
To determine the phenotype of the LM and LN blood
cells a very specific set of antibodies is
required. The anti- LM antibodies specifically
recognize the LM blood-cell surface proteins and
the anti LN antibodies specifically recognize the
LN surface proteins. In practice, specific
recognition by each antibody results in
precipitation of the red-blood cells. This is
because each antibody actually has two functional
binding sites enabling extensive cross-linking to
occur.
So with the anti- LM and anti- LN antibodies, one
can determine which form of the L gene (LM or LN)
is being expressed in each individual
32
Genotype Phenotype RBC surface Antigen
expressed Precipitation by ?- LN ?- LM
In this case, the heterozygote is expressing both
proteins. Therefore, with respect to RBC
expression of LM and LN protein these alleles
are co-dominant
33
Blood groups
Genotype Phenotype RBC surface Antigen
expressed Precipitation by ?- LN ?- LM LM LM
No Yes LM LN LN Yes No LN LN LM
Yes Yes LM and LN
In this case, the heterozygote is expressing both
proteins. Therefore, with respect to RBC
expression of LM and LN protein these alleles
are co-dominant P LM LM x LN LN F1
LM LN F2 LM LM LM LN LN LN 1 2 1
34
Paternity issues
Paternity issues The M and N blood typing can be
used to disprove that an individual was the
biological father of a child. For example if the
mother expressed only the M antigen, she could be
only of one genotype- LMLM. If the child was of
the genotype LMLN, we know the biological father
must possess at least one LN allele. Mother's
genotype Father's genotype LMLM
x LMLN or LNLN This technique only
rule out potential fathers. It cannot prove that
an individual is the father. As you will learn
later in the course, DNA fingerprints can
actually be used to identify the individual
father.
35
Phenotypes
When examining a dominance relationship between
two alleles, we compare genotype to phenotype.
Specifically we look at the genotype of the
heterozygote. With respect to the M and N blood
group the phenotype is different than that of
which we are used to. We have discussed pea
shape, flower color, morphology and behavior as
phenotypes. These are all properties that are
easily visualized. However with specialized
tools, microscopes and specific probes such as
antibodies we can detect less easily visualized
phenotypes.This indicates that the phenotype has
subjective nature to it. It depends on the way
the observer chooses to define it. This in turn
depends on the individual's powers of observation
and the tools available. For example, shown below
are a normal and a mutant Drosophila wing. What
is the difference?
Wild-type
Mutant
36
Sickle cell anemia
Sickle cell anemia is a good example of the
variance in dominance relationships. Sickle cell
is an inherited disorder that results from a
mutation in the gene coding for the protein
globin. Hemoglobin is a major constituent of the
red blood cells and is involved in O2
transport. HbA an allele that codes for the
normal hemoglobin protein HbS an allele that
codes for an abnormal form of hemoglobin We will
examine the phenotype of the two homozygotes and
the heterozygote at three levels the
individual, the cell the protein. Normal O2
levels Low O2 levels (Sea level) (High
altitude) Depending on the O2 levels, the
HBS allele (and the HBA allele) behaves as a
dominant or recessive. Remember, the phenotype
of the heterozygote is the key to understanding
whether a gene behaves as a dominant or recessive.
37
Genes and their products
Genes and their products (primarily proteins) do
not function in isolation, they interact with the
environment. What is the cellular phenotype with
respect to these genotypes The HBS allelic form
of the protein causes the red blood cells to
sickle. Cell shape HbA/HbA Normal
shape HbS/HbS Sickled HBS/HbA Partially
sickled At this level the alleles HbA and
HBs are incompletely dominant
38
Phenotype at the level of the protein.
-

HbA/HbA
HbS/HbS
HbA/HbS
With respect to the proteins HbS and HbA are
co-dominant
So the HbS allele is classified differently
depending on the level the phenotype is analyzed
Individual Cell Protein
39
Fitness
Individuals homozygous for HbS/HbS often die in
childhood. Yet, the frequency of the HbS allele
is quite high in some regions of the world. In
parts of Africa frequencies of 20 to 40 are
often found for the HbS allele. It was found
however that in areas in which there was a high
HbS allelic frequency, that there was also a
corresponding high frequency of mosquitoes
infected with the protozoan parasite, plasmodium.
This parasite causes Malaria in humans. It was
proposed and later proven that heterozygous
HbA/HbS individuals are more resistant to the
mosquito born parasite. Consequently this allele
in maintained in the population in spite of its
deleterious consequences in the homozygous state.
This condition in which the heterozygote is more
fit than either of the two homozygotes is known
as a balanced polymorphism (over dominance,
heterozygote advantage) HbA/HbA
HbA/HbS HbS/HbS