1. Human Inheritance Notes Ch. 14 - Part II
Sex-Linked and Autosomal
Genetic Disorders

2. Karyotype Chart Karyotype interactive
Once the cells have been gathered, scientists will take a picture of the chromosomes and make a karyotype chart.
Karyotypes show the 23 homologous pairs for the person in which the cells were taken.
The pairs are put in order from longest to shortest and numbered from 1 to 23.
Pairs 1-22 are called autosomes.
Pair 23 are the sex chromosomes.
Karyotype interactive

3. Is this a Male or Female Karyotype chart?
Female- XX

4. Down Syndrome Cells contain one extra copy of chromosome # 21.
This results in:
characteristic facial features
short stature
mental retardation
shorter life-span
Increased risk for heart problems, immune system problems, and cancer.
Chromosome number disorders link
Down Syndrome link

5. Klinefelter Syndrome This results in a male who has
one extra X chromosome.
47,XXY
This results in
This male can not have children.
He can show mental retardation.
Is a true male, but can have some female characteristics.
Klinefelter Syndrome Link

6. Sex-linked Inheritance (carried on the X chromosome)
Sex-linked disorders are more commonly seen in males.
Genes carried on the X chromosome are said to be sex-linked traits.
A carrier is a person who is heterozygous for a disorder, but does not show the disorder
Carriers of sex-linked traits are female.

7. Sex-linked Disorders (carried on the X chromosome)
Example 1 : Hemophilia
a recessive allele written as Xh
What is hemophilia? “free bleeders”
A clotting protein is missing.
Uncontrolled bleeding can occur from wounds and bruises.
Affects 1 out of every 10,000 males

8. Female with Hemophilia
Phenotype
Genotype
Normal Female
XHXH
Carrier Female
XHXh
Female with Hemophilia
XhXh
Normal Male
XHY
Male with Hemophilia
XhY

9. Y XH XHXH XHY Xh XH XHXh XhY
Problem 1: A normal man marries a woman who is a carrier.
Create a Punnett square to determine the probability of passing on the allele to their offspring. Y XH
What are their chances of having a
daughter with hemophilia? 0%
a daughter who is a carrier? 25%
XHXH
XHY Xh XH
XHXh
XhY
a normal son? 25%
a son with hemophilia? 25%

10. Sex-linked Disorders (carried on the X chromosome)
Example 1 : Colorblindness
a recessive allele written as Xc
What is the most common form of colorblindness?
Condition where the person cannot distinguish between the colors red and green.
Affects 1 out of every 10 males and 1 and 100 females.

11. Y Xc Xc XC+ XC+Xc XC+Y XcXc XcY
Problem 1: A color-blind man marries a woman who is a carrier.
Create a Punnett square to determine the probability of passing on the allele to their offspring. Y Xc
What are their chances of having a
daughter with normal vision 25%
a daughter who is a carrier? 25% Xc
XC+
XC+Xc
XC+Y
XcXc
XcY
a normal son? 25%
a color-blind son? 25%

12. How can we tell if a genetic disorder is sex-linked?
Is a sex-linked trait more often seen in males or females? Why?
Sex-linked traits are seen more often in males because males only have to inherit one copy of the trait on the X chromosome he received from his mom!

13. Sex-linked Disorders (carried on the X chromosome)
Example 3 : Duchenne Muscular Dystrophy
a recessive allele written as Xd
What is muscular dystrophy?
A disorder that causes the muscles to slowly weaken and eventually leads to death.
Affects 1 out of every 3,000 males

14. Autosomal Disorders
These are disorders carried on the autosomes, rather than the sex-chromosomes.
Most genetic disorders are recessive.
Recessive disordered alleles produce proteins that either malfunction or no longer function.
A heterozygous carrier has a normal phenotype because the one “normal” allele produces enough of the required protein.

15. Recessive Autosomal Disorders Albinism
Caused by a recessive allele on the chromosome 11.
Individuals who are homozygous recessive are unable to produce melanin, the pigment responsible for human skin color.
They have no pigment in their hair or skin, and are sensitive to light.

16. Recessive Autosomal Disorders Cystic Fibrosis
Caused by a recessive allele on chromosome 7.
Found in 1 in every 2,500 Caucasian births. 1 in 25 are carriers.
Individuals who are homozygous recessive make a defective cell membrane protein.
This creates extra mucus that clogs the lungs and breathing passageways leads to bacterial infections.
Two carriers have a 25% chance of having a child with cystic fibrosis.

17. Dominant Autosomal Disorders
Dominant disorders are typically lethal and are extremely rare.
This is because if a person inherits it he or she dies before they can have children.
Exceptions:

18. Huntington Disease
This caused by a rare dominant allele on chromosome 4. 1/25,000 affected.
Symptoms start with a loss of muscle control.
*No symptoms until age 30 to 40. Mortality within 15 years after systems first appear.
The gene for Huntington disease is dominant, so that every child of a person with the disease has a 50% chance of inheriting the gene and having the disease.
*This is a lethal disorder, homozygous dominant fetus, the baby miscarries.

19. Huntington Disease
*This is a lethal disorder, which means if a person is homozygous dominant the baby miscarries.
*No symptoms until age 30 to 40.
*Why could not showing the disease until later in life be a problem? A person who doesn’t know they have the disorder can pass it on to their children before they show the disease.

20. Sickle Cell Anemia
(codominant disorder) It is found in 1 out of every 1,600 African Americans.
It is an anemia due to the sickled allele producing an alternate from of hemoglobin (red blood protein), which causes cells to sickle or become crescent shaped.
Individuals with two sickle cell alleles are said to have sickle cell anemia.
It can lead to serious medical problems with sickled cells forming blood clots.

21. The family tree of genetics
Pedigree Charts
The family tree of genetics
What is a pedigree?
Constructing a pedigree
Interpreting a pedigree
A quick refresher for the teacher on important terms:
Autosomal gene- a gene found on any chromosome except for the sex chromosome. These are chromosomes numbered 1-22.
X-linked gene- a gene found on a chromosome designated as a sex chromosome (X or Y).
Dominant- Refers to an allele that is expressed phenotypically and masks any recessive counterpart.
Recessive- An allele that is not phenotypically expressed when its counterpart is dominant.

22. What is a Pedigree Chart?
A Pedigree chart traces the inheritance of a particular trait through several generations.
One GOAL of using a pedigree chart is to figure out who are carriers of the trait, because this information is typically unknown.
A pedigree is a chart of the genetic history of family over several generations. Scientists or a genetic counselor would find out about your family history and make this chart to analyze it. For example, a couple might like to know their chances of having a child that has muscular dystrophy. So the scientists or a genetic counselor would find out who had muscular dystrophy in the mother’s and/or father’s families. This information would be used to and then calculate the probability of the couple having a child with MD.

23. Constructing a Pedigree
Female
Male
You must learn the symbols of the pedigree charts before you can start to learn how to interpret it. These are the symbols that represent a male and a female.

24. Constructing a Pedigree
Married Couple-
Horizontal Line
Siblings
Vertical line
More than one Sibling:
a horizontal line is drawn with a vertical line coming down for each sibling.
These symbols also represent relationships between people. some may have to each other.

25. Constructing a Pedigree
Fraternal twins-
Two line branching from the same point
two eggs and two sperm cells.
Identical twins-
Also called Maternal Twins
Same as fraternal twins but a horizontal line is added.
one egg and one sperm unite and later splits to form two babies
Here are examples of symbols that represent relationships between people.

26. Constructing a Pedigree
Roman numerals to the left of the pedigree show the generations.
Birth Order: children are listed in birth order with oldest on left and youngest on the right. I II
III
This is just an example of a pedigree and there can be many more different types.

27. Constructing a Pedigree
Two horizontal lines from the same person represent two marriages / matings.
Example:
This man first had a girl with the lady on the left, then had a boy and girl with the lady on the right.

28. More Symbols in a Pedigree Chart
Full Shaded:
Affected person who shows a disorder
Half shaded:
Autosomal carrier
Circle with dot:
X-linked carrier –always female
Deceased
These are examples of different types of symbols. These symbols would be the same for males or for females, except for X-linked carrier which is only used for females. So an affected male would be a square that is filled in completely. A deceased female would be a circle with a diagonal slash.

29. Predicting using Pedigree Charts
Pedigrees are used to find out:
who are carriers of the disorder &
the probability of having a future child with the disorder.
To begin to interpret a pedigree, first determine if the disorder is:
Autosomal dominant
Autosomal recessive
Sex-linked (carried on the X chromosome)
This summary will help reiterate the important parts of this lesson.
[Created by Lauren Almaguer, CDC Science Ambassador, 2004.]

30. Interpreting a Pedigree Chart
First ask:
Is it a Sex-linked or Autosomal Disorder?
If there is a much larger number of males than females who are affected then the disorder is Sex-linked.
If there is a 50/50 ratio between males and females who are affected then the disorder is autosomal.
When interpreting a pedigree chart of a family with a disease like muscular dystrophy, it is important to consider two steps. The first is to determine if the disorder is autosomal or X-linked.
If the disorder is X-linked most of the males will have the disorder because the Y-chromosome cannot mask the affects of an affected X-chromosome. A female can have the disorder, but it would be a very low percentage. For a female to be affected, she would have had to receive an affected gene from the mother and the father. This means that the father would have the disorder and the mother was a carrier.
In an autosomal disorder, the disorder is not found on the X or Y chromosome. It is found on the other 22 chromosomes in the human body. This means that men and women have an equal chance of having the disorder. The mother and father can be homozygous dominant, heterozygous, and homozygous recessive. If a person is homozygous dominant, the person has two of the same dominant genes. For example if someone is homozygous dominant for being tall it may be represented as TT. Capital letter always represent a dominant gene. If a person is heterozygous, this person would have a dominant trait and a recessive trait. It may be represent as Tt. The dominant gene will mask the recessive gene, so the person is still tall. If a person is homozygous recessive, the person has two of the same recessive genes. For example if someone is homozygous recessive for height, it may be represented as tt. The tt would mean the person is short.

31. Interpreting a Pedigree Chart
If it is autosomal disorder then ask:
Is it dominant or recessive?
If two parents do not show the trait and their children do show it, then it is an autosomal recessive disorder
(parents are heterozygous)
If the disorder is autosomal dominant, then at least one of the parents must show the disorder.
The second step is to determine if the disorder is dominant or recessive. It is important to find out if a disorder is dominant or recessive. For example, Huntington’s disease is a dominant disorder. If you have only one dominant gene you will have Huntington’s disease, which is a lethal disorder. The disorder does not show up until a person is in their middle ages such as 45. It will quickly decrease their motor skills and the brain will begin to deteriorate.
If a disorder is dominant, one parent must have the disorder (either homozygous dominant (TT) or heterozygous recessive (Tt). Both parents do not have to have the disorder. One parent might not have the disorder or be a carrier. If a disease is dominant, it does not skip a generation unless one parent is heterozygous dominant (Tt) and the other parent is homozygous recessive (tt). In this case the child has a chance of not receiving the dominant gene.
If the disorder is recessive, a parent does not have to have the disorder, but could still pass it to their offspring. This would happen when a parent is heterozygous recessive (Tt) and passes on the recessive (t) gene. This means this disorder can skip generations. An example of a recessive disorder would be sickle cell anemia.

32. Practice Examples Sex-linked or Autosomal disorder?
Does this pedigree show a
Sex-linked or Autosomal disorder?
Take a minute and try to decide if this slide is autosomal or X-linked.

33. much larger number of males are affected
Answer:
Sex-Linked Disorder
much larger number of males are affected
Take a minute and try to decide if this slide is autosomal or X-linked.

34. Practice Examples Sex-linked or Autosomal disorder?
Does this pedigree show a
Sex-linked or Autosomal disorder?
Take a minute and try to decide if this slide is autosomal or X-linked.

35. 50/50 ratio between males and females
Answer:
Autosomal Disorder
50/50 ratio between males and females
Take a minute and try to decide if this slide is autosomal or X-linked.