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PEDIGREE-CHROMOSOMAL
ABNORMALITIES
BEGINS
Hi there dudes and dudettes! We’re the teenage Mutant Ninja Turtles and we are here
not only to fight crime but to learn along with you about pedigrees and chromosomal
abnormalities! Now our arch enemy, Shredder, has ambitions to take over the world and
he will be using his knowledge to fight us. Our job is to stop his evil plans with the help
of you biological expertise
Here is a little about our history. We four turtles and a rat took on human-like form
when we were exposed to a mutagenic gel in a sewer. Splinter, the rat, our mentor,
taught us jinjitsu and teaches us wisdom. Since then we have been fighting evil. Now
we need you to join our NINJA TEAM!
The ninja arose as a peasant class mercenary fighter as opposed to the samurai warrior
class. They were capable of more covert operations than the samurai and were practiced
spies, raiders, surprise attackers, assassins, scouts..., all jobs considered not respectable
for the conventional warriors.
I am Splinter, the advisor to
these turtles who wish to fight
all that is evil. Now as you
enter our ranks, you will be
known as GRASSHOPPER.
Before we begin, let us
understand the pedigree
analysis.
Human inquiry into our own genetics has been a challenge. Humans have
generation times of about 20 years and produce relatively few offspring.
One of the ways humans can be studied is with the use of pedigrees. The
pedigree is like a family tree where one genetic trait is followed through many
generations.
IN THE PEDIGREE.............
= FEMALE
= MALE
Horizontal line connecting is a
marriage line
Vertical line followed by
horizontal is for offspring
Oldest children are on the left to
youngest on the right.
Here are more
symbols that are
used on the
pedigree.
Memorize them
so you will
understand the
pedigree like a
Ninja. You may
need the
information to
fight your
enemy!
Splinter, what is the
difference between
monozygotic and dizygotic
twins?
Dizygotic twins are fraternal twins. They arise from
the fertilization of two eggs by two sperm. Even
though the two children are born at the same time,
they are no more related than brother and sister.
Also different sexes are possible which is not the case
with the monozygotic (identical) twins.
You should be able to
answer that yourself from
the derivation of the
words. Mono means one
and zygote is the first cell
of a living being. Thus
Monozygotic twins arose
from one egg – They are
commonly called identical
twins as their genetics
DNA are the exact same.
All right young Ninja. Try to knock me, Shredder
off this pedigree stand before I can attack you!
Question 1 How many deaths are indicated?
THINK THINK THINK
There are three indicated
deaths with ages listed.
Question 2. What is the P1
composition of the original family?
THINK THINK THINK
Two older boys –youngest -girl
Question 3. Is the trait a dominant or recessive?
Sex linked? All affected individuals are girls!
THINK THINK THINK
Recessive autosomal – no sex link --girls may be
predisposed - breast ovarian cancer
You win this
time young
Ninja!
Examine the gene for sickle cell anemia. See what you can find out.
Sickle cell anemia is caused by a single substitution
mutation. One amino acid in a total of 287 is incorrect
leading to a change in the primary structure of the
amino acid chain. Glutamic acid is replaced by Valine
with normal
Sickle blood cells, shown left, get
stuck in blood vessels leading to
circulatory problems.
The gene is found in individuals of African
descent. The gene is considered recessive
but is really a codominant gene as
heterozygotes produce both normal and
sickle cell blood. Homozygotes suffer fully
from sickle cell anemia because they make
only sickle shaped red blood cells.
Sickle cell anemia on beta chain of the
hemoglobin gene
Hemoglobin has two chains that make the
protein alpha and beta
That is good, young grasshopper. But how does this
relate to overall genetics. How has it persisted through
the years in this population?
The heterozygote sickle cell anemia person
seems to have some resistance to malaria, a
disease that has been responsible for killing
millions of people over thousands of years on
the African continent. It also seems to be
connected with increased fertility for
heterozygote mothers. These two factors would
make the gene increase in frequency within the
population.
Here heterozygotes are represented
by the diagonal lines
Here is an
example of
the
pedigree for
sickle cell
anemia.
Can you tell
why young
grasshopper
?
The cross between I 1 and 2 would give you a punnett
square with one normal, two heterzygotes and one
affected by sickle cell. In this family the oldest boy is
heterozygous, middle girl, sickle cell and youngest girl
homozygous normal. Only 3 kids but fairly accurate to
the punnett expectations
Grasshopper, I don’t think you are correct thinking
this is a sickle cell anemia pedigree. Take a look at
cross II 1 and 2. There are no carriers in the
offspring. Can I destroy you now?
While it is true that the cross would make a
punnett square with 50% normal and 50%
heterozygote, due to random chance, both
children could inherit the dual normal genes.
Take a look at this extensive pedigree, young Grasshopper. You will notice
some very important people that you should be familiar with. Coloured in
blocks indicate people with hemophilia. This pedigree may have changed the
modern world. Can you determine why?
You are foolish, young Grasshopper, to tangle with me. Your
wits are no match. You probably will even confuse the sickle
cell with hemophilia because they are both blood disorders.
Just wait until you face me alone!!
Don’t sweat, we can handle
him right now, right dudes?
Hemophilia is caused by a sex-linked recessive allele located
on the X chromosome. These people have a blood clotting
problem and until recently, the disease was untreatable. In
the old days, only a few hemophiliacs survived to reproductive
age because even a small cut could be fatal.
Today, blood transfusions provide hemophiliacs with the
necessary clotting factor that they lack.
Hemophilia is present in males much more frequently than
females. Since males are hemizygous at the X allele (there
is only one), if they get the defective X chromosome, there
is no other X chromosome to compensate.
Since I’m a girl, I have
two X chromosomes
and I would have to get
both defective X
chromosomes for it to
show up in my
phenotype
Shucks, I only got one X
chromosome. If it is defective, it
will show up in my phenotype.
Normal woman x hemophiliac man
Take a look at this punnet square. The man
here is a hemophiliac, yet none of his
children actually end up having hemophilia.
The daughters, however, are all carriers of
the hemophilia gene, even though they do
not suffer from hemophilia.
The real culprit that transfers the hemophilia is the female
carrier. If a normal man marries a female carrier of
hemophilia, the punnet indicates a probability of 50% of the
sons having hemophilia. Daughters would not have the
disorder, but one half of them also would be carriers of
hemophilia like their mother.
In this punnet B is the normal gene and
b is the recessive hemophilia gene.
Carrier daughter
Hemophiliac son
hemophilia
Let us get back to the story of the
hemophilia pedigree. Here is a more
detailed analysis of Leopold, Queen
Victoria’s eighth child. All his life, he
was delicate and treated with extreme
care as any bump could lead to fatal
hemorrhage. You can see that the
disease skips a generation as neither of
his children actually have the disease.
The daughter however, is a carrier and
passes the disease on to her son
Rupert. The daughter Lady May
appears to be the lucky recipient of her
mother’s one good X chromosome as
her marriage does not result in any
children with hemophilia.
Leopald died at age 32 of
hemorrhage.
What about the current royal family. Could Queen
Elizabeth’s offspring eventually pass the genetics of
hemophilia on to future royal sons
I do not carry the hemophilia gene and
although I am a descendent of Queen
Victoria, neither I nor any of my royal house
starting with my great grandfather, King
Edward VII of England have ever had
hemophilia
How do you know your children were not infected by your husband, prince Phillip.
You know I am not blind, I looked at the pedigree and it indicates that he also is
descended from Queen Victoria! I think he would be classified as your cousin!
Shredder, don’t insult the Queen. It just shows how little
you know. If you would have been listening, you would
realize that since prince Philip is normal, it is not possible
for him to have the defective X chromosome.
Did you know that Prince Philip’s grandfather’s sister was
married to the Czar of Russia --That is the King of Russia.
As you know there is no longer a royal house in Russia
and for a very long time Russia was a communist
country. Could the Curse of the Romanovs (the Czar’s
family) be connected to hemophilia? You be the judge.
It all started with what appears to be defective
eggs from Queen Victoria that seemed to have
the hemophilia gene on their X chromosome.
It is likely this mutation event started the
entire hemophilia disorder which became
widespread as many royal houses married into
this disorder. ROYALS ONLY MARRY OTHER
ROYALS and so their genetics become very
similar over time. In this picture is Alix, grand
daughter to marry the Czar
Nicholas and Alix had 4 daughters, the youngest named
ANASTASIA of some popular fame. Nicholas needed,
however a male heir to the Russian throne and finally,
Alexis was born but he had the hemophilia gene passed
along from Queen Victoria. The affliction resulted in
delicate treatment, but also introduced the potential for
outside false hope treatments. Rasputin came to influence
in the Romanov court as a result. How much this
contributed to the downfall of the Romanov reign is
debatable, but still very possible.
Nicholas II abdicated as he lost control of his country in 1917 with WW I stresses largely
contributing to Russian misery. The Bolshevik revolution occurred bringing communism to
Russia and the Czar, wife and all children were brutally executed and thrown into a well.
Communist Russia largely defeated Hitler’s greatest armies during the second World War
and Stalin became the face of Russia Stalin enslaved Eastern Europe after WWII and
developed atomic weapons to begin the COLD WAR.
And you thought
Finally in our modern times, the Cold War has ended and
understanding
Russia is no longer communist. Would all this be the same
biology was
had Nicholas’s son been normal? Who is to say? Just think
isolated to
of how history would have been affected. –
scientists!!
Now back to my interrogation of you young grasshopper!
Excuse me brave warrior, but could I
ask you a question? You do not
happen to have six fingers on your
right hand do you?
No I don’t. Who are you and why do
you ask such a strange question?
I, Inigo Montoya, am searching for the six fingered man. He
killed my father and all my life has been dedicated to finding
and killing him to avenge my father.
Polydactyly (extra fingers or toes) is a dominant
autosomal disorder. For those of you who think
dominant alleles are always prevalent in the
population, think again!! Here is an example where the
dominant allele is obviously very low in occurence.
B= dominant allele
polydactyly
Bb
bb
Bb
bb
b = normal
allele
This is the
pedigree of a
dominant allele.
You can notice that
when an affected
individual marries
a normal
individual, the
probability of the
child being
affected is about
50%. This means
that all the
affected
individuals in this
pedigree are
heterozygous.
Dominant inherited diseases are very rare, because victims of these diseases tend to die
before reproducing, and thus passing on the gene for the disease. As a result, the few
dominant inherited diseases that do exist rarely manifest themselves before late middle
age. Polydactyly is of course an exception.
HUNTINGTON’S DISEASE is caused by an autosomal dominant allele and so is
HYPERCHOLESTEROLEMIA
You can see from the pedigree
that this does not skip
generations. It appears in
about 50% of the children and
thus is due to the dominant
allele. All affected individuals
here are heterozygous.
HUNTINGTONS – Symptoms appear middle age dementia + jerking
movements.
HYPERCHOLESTEROLEMIA – high levels of LDL cholesterol in bloodcauses heart disease arteriosclerosis.
Solve the pedigree
So what do you think about this
pedigree Grasshopper?
1. It is not X linked as it is passed from a father to the son. This
never happens with X linkage
2.Males and females are affected, with roughly the same
probability No x linkage
3.The disease occurs in three consecutive generations. It must
be dominant as this never happens with recessive traits
4.The disease is likely Huntingtons indicated by HD in the
chart and knowing it as a dominant.
Hey Splinter, one of our friends has
PKU. We have to leave out anything
that contains the amino acid
phenylalanine on the pizza order.
What is his problem?
Children with this disorder must be screened for when born.
They cannot metabolize the phenylanaline and it accumulates
in their brain reaching toxic levels. This of course would cause
mental retardation. If, however, phenylalanine in the diet is
avoided, the child can live a normal life. Check the pedigree
Hey I see the
marriage line is
consauginous.
That means the
parents were
both blood
relatives!
COUSINS!!
The disease is due to an
autosomal recessive
gene. Neither parent nor
grandparent had it.
Is it legal to
marry your
first cousin?
That is correct Turtles. It is also one of the
reasons why marriage between siblings is
considered taboo. You see, you are more
genetically similar to your brother or sister than
anyone else. Thus your chances of having
double recessive alleles combine in the offspring
of brother and sister is much higher than
normal. In this particular case, both cousins
carried the PKU gene and when they married
and had children, the probability of the PKU
child was 1/4
We learned that in the general population about 1 in
50 people are carriers for the detrimental allele.
I heard it was legal in Florida,
but not most states.
Hey, this is a 10. The
tab is 13.
Wise man say forgiveness is
divine, but never pay full price for
late pizza.
You're two
minutes late,
dude
Aw come on, I
couldn't find the
place!
Tay Sachs is an autosomal recessive
disorder that is more common within
the Jewish community. Since their
religion has meant they stayed
I gotta get a new route. And I
thought I delivered
within their gene pools for
everywhere
reproduction, more double recessive
combinations are possible between
Tay Sachs results in progressive
these people who are more related
loss of neurological function.
to each other than people in the
Children usually die before age 5
general population.
Before I leave you to deal with Shredder, I will
discuss one further disease scenario
1.This is an example of a recessive disorder. You can notice that neither of
the parents nor grandparents has expression of the disease.
2. It is relatively
equal between
male and
female not X
linked
3. It happened to
two children out
of six which is
close to the ¼
double recessive
combo
Cystic fibrosis
4. Both parents II 1 + 2 were
heterozygous for cystic fibrosis to
produce the affected cystic
fibrosis children
Cystic Fibrosis is an autosomal recessive caused disease. It
causes the lungs to fill with mucous and organs to clog with
fluid. It causes stunted growth and general weakness. People
with this disease generally died in childhood but modern
medical techniques have extended their life-spans.
The underlying reason for the problem is a defective CFTR structure due to mutation.
This structure does not provide correct chloride re-entry to secretory epithelial cells.
Chloride on the outside draws water out of the cell causing fluid build up.
Now it is my turn to tear your young
trainee, called Grasshopper, apart! Ha ha
ha ha! Interpret the pedigree.
And
the
questi
on
mark?
It appears to be recessive --- autosomal most likely
Chances are ¼ that the individual will be affected.
You fight well...
in the old style.
But you've
caused me
enough trouble
Now solve this
pedigree
Grasshopper!
1.It passes through the generations
without skipping. It is dominant
2. It affects the males and females the
same. Thus not X linked.
3.Affected fathers have affected sons –
not x linked.
1. The genes do not skip generations –
Appears dominant.
Interpret this
pedigree
Grasshopper
2. More males do seem to get the
disorder, but affected fathers will pass it
on to affected sons. This indicates it is
not x linked.
Conclusion– dominant autosomal
Try this one!!
Dude, this one is special. Notice how
sons inherit it from the heterozygous
mother.
And it looks like it affects males rather
than females
It can skip generations and
disappear
It must be x linked recessive
And this one?
1. Skips generations –likely recessive
2. Arises from unaffected parents –
points to recessive
3. Equal male female distribution – seems
not x linked – probably autosomal.
CONCLUSION
AUTOSOMAL
RECESSIVE.
How about this one?
Must be a carrier
1. Males do not pass it to sons –looks like x linked
2. Affected people are mostly male – looks x linked
3. Heterozygotes are always female- x – linked carriers
recessive allele
CONCLUSION – SEX LINKED RECESSIVE
I am defeated!!
Ahhhhhhh!
I am proud of you, my sons. Tonight you have learned
the final and greatest truth of the Ninja: that ultimate
mastering comes not from the body, but from the
mind. Together, there is nothing your four turtle
minds plus one Grasshopper mind cannot accomplish.
Help each other, draw upon one another, and always
remember the power that binds you. The same is
what brought me here tonight, that which I gladly
return with my final words: I love you all, my sons.
Cowabunga
dudes!!
PEDIGREE-CHROMOSOMAL
ABNORMALITIES
The end