Chapter 14 Notes: Karyotypes

I. Human Chromosomes

A. Humans have 46 chromosomes (diploid-2N)

1. 2 of them are sex chromosomes (X and Y)they determine what sex you are

a. XX = female

b. XY = male

Sex chromosomes

Is this offspring a girl or boy? How do you know?

2. 44 of them are autosomes they do notdetermine the sex of an individual.

B. How is a Karyogram Made?

1. To examine human chromosomes, biologist photograph cells in mitosis when the chromosomes are fully condensed (“X” or rod structure)

2. Cut out the chromosomes from a chromosome spread then arrange to match the banding patterns of the homologous pairs

3. This type of picture is called a KARYOGRAM

C. What does a Karyotype tell you?

1. Sex (male or female)

2. Irregular numbers of chromosomes

3. Any mutations in the chromosomes

Figure 1 Karyotype from a 10-year-old female with acute myeloid leukemia (AML) with

abnormal bone marrow eosinophils and the characteristic inverted chromosome 16 (arrow). This

inversion results in a fusion between CBFB on the long arm that codes for a subunit of a DNA

binding protein complex and the MYH11 gene on the short arm that codes for the smooth muscle

form of myosin heavy chain protein. The fusion protein is thought to interact with the AML1

transcription factor and increase its ability to bind to DNA and regulate transcription.

46,XX,inv(16)(p13q22)

4. Basically: all the chromosomes in a cell are displayed and can be examined for abnormalities

http://what-when-how.com/genetics/acquired-chromosome-abnormalities-the-cytogenetics-of-cancer-genetics/

Are there any abnormalities in this offspring?

II. Chromosomal Disorders

A. Most of the time, the mechanisms that separate human chromosomes in meiosis work very well, but things can go wrong

1. The most common error: NONDISJUNCTION

a. The chromosomes fail to separate

b. The result? Abnormal numbers of chromosomes

Trisomy

47 ChromosomesMonosomy

45 Chromosomes

Nondisjunction

Normal

Cell

Division

Gametes

Meiosis

Female Male

2. Examples of Chromosomal Disorders due to nondisjunction

a. Down Syndrome

b. Klinefelter’s Syndrome

c. Turner’s Syndrome

d. Triple X Syndrome

B. Chromosomes Affected:

1. Down's Syndrome: 47 chromosomes with 3 #21 chromosomes.

2. Klinefelter's Syndrome: 47 chromosomes caused by 2 X chromosomes and 1 Ychromosomes.

3. Turner's Syndrome: 45 chromosomes with 1 X chromosome (caused by the absence of one of the X chromosomes or a Y chromosome).

4. Triple-X Syndrome: 47 chromosomes caused by 3 X chromosomes.

C. Down Syndrome

1. 47 chromosomes total due to 3 copies of chromosome #21

Chris Burke

“Corky”

Late 80’s early

90’s TV show

“Life Goes On” 1st

Character on

Network TV w/

Down Syndrome

2. 1 in 800 babies in the US is born with this disease

3. Produces mild to severe mental impairment

4. May not live as long

D. Klinefelter’s Syndrome

1. This is a sex chromosomal disorder associated with males.

2. Nondisjunction causes an extra X chromosome to be passed along during

meiosis (XXY).

3. Resulting male cannot reproduce (sterile)

4. Decrease muscle massand body hair

5. Cases have been found in which individuals were (XXXY) or (XXXXY)

6. 1/2000 births

E. Turner’s Syndrome

1. This is a sex chromosomal disorder associated with females.

2. Nondisjunction causes offspring to inherit only one X chromosome (genotype = XO).

3. Resulting female is sterile due to underdeveloped sex organs.

4. 1/2500 Females born

5. 90% are naturally aborted before bornHollywood Actress Linda Hunt

F. Triple X Syndrome

1. This is a sex chromosomal disorder associated with females.

2. 47 Chromosomes, XXX

3. Female looks normal, is fertile

4. Increased learning disabilities, delayed motor skills

5. 1/1000 females born5 to 10 girls with triple X syndrome are

born in the United States each day

G. Other Nondisjunction Disorders:

1. XYY Syndrome

a. Physically active boy, normal sex organs, delayed mental maturation, and in connection with an increased tendency for learning-problems in school

b. Intelligence is usually in the normal range, although IQ is on average 10-15 points lower than siblings.

c. Usually very tall (average of 6’ 3” as an adult), many experience severe acne during adolescence

2. YO syndromea. Embryo would not formb. No implantation in uterusc. Female would not know that fertilization

occurred

X Chromosome is necessary for growth and development

Chromosomal Mutations (from 12-4)

Chromosomal Mutations

• Deletion

• Duplication

• Inversion

• Translocation

III. Review question: Who determines the sex of a child?

A. The mother or the father?

1. THE FATHER!

B. Why does the fatherdetermine the sex of the offspring???

1. Mom is XX: she can donate either one Xchromosome or the other X chromosome to the offspring (mom can only donate an X)

2. Dad is XY: he can donate either an Xchromosome or a Ychromosomes.

a. If the offspring receives an X from dad, it is female

b. If the offspring receives a Y from dad, it is male

Chapter 14 Notes: Pedigree Charts & Sex-linked

I. Pedigree Chart

A. Definition: Visual representation of how a

trait is transmitted from generation to

generation

1. Each row represents a generation

2. Circles represent females

3. Squares represent males

4. Shaded in: person expresses that trait

5. Half shaded in: person is only a carrier (not always provided)

a. Carrier= a person who carries the allele for the trait but does not express the trait

b. Carrier’s genotype= Ff

i. Unless it is a dominant disorder / condition-then need only 1 allele to express the trait

c. Example: Cystic Fibrosis

i. For a person to have Cystic Fibrosis (genotype=ff), he or she must have inherited an “f” from both parents

ii. Therefore, BOTH parents must be carriers(both Ff)

6. Clear: person does not express that trait (BUT could be a carrier—look at the next generation)

B. Genetic Counselors use pedigree charts to trace genes (the lineage of genes) in a family.

1. This is very important for tracing the lineage of diseases in a family.

2. You can find out how a disease is inheritedand the chances that this disease will be passed down to the next generation!

3. HOWEVER…..You can’t trace every human trait through a pedigree because some genesare polygenic

4. What does this mean again?....Controlled by more than 1 gene.

5. Examples of polygenic traits:

a. Shape of your eyes

b. Shape of your ears

c. Height

d. Eye color

6. Also, phenotype is influenced by your environment (ex: nutrition & exercise)

a. Average height is 10cm more than it was in the 1800’s in the US & Europe due to nutritional improvements

Cataracts can be inherited or caused by

the environment

b. Genes that are denied a proper environmentin which to reach full expression in 1 generation, can achieve full potential in a later generation (genes are inherited, the environment is not)

II. Chromosomal Disorders

A. Autosomal Disorders

1. Disorders that are not sex-linked (must be located on the autosomes, NOT the sex chromosomes!)

2. Can be autosomal recessive or autosomal dominant

3. Autosomal recessive

a. This means that you need two recessivealleles (on any of the 44 chromosomes—NOT the sex chromosomes) to express the disease

B. Autosomal recessive diseases:

1. PKU

2. Tay-Sachs

3. Cystic Fibrosis

Autosomal recessive inheritance.

http://www.merck.com/mmpe/sec22/ch327/ch327b.html?qt=symbols&alt=sh

Cystic fibrosis

http://www.nlm.nih.gov/medlineplus/ency/imagepages/18135.htm

4. Albinism

C. Autosomal dominant disorders

1. Only one allele is needed for the trait to be expressed (to show up in the offspring)

a. Huntington Disease

genetic neurological

disorder

characterized after

onset by

uncoordinated, jerky

body movements and

a decline in some

mental abilities

Autosomal dominant inheritance

http://www.merck.com/mmpe/sec22/ch327/ch327b.html?qt=symbols&alt=sh

Ex: Marfan syndrome-connective tissue disorder

Huntington's disease-neurological disorder

b. Achondroplasia (Dwarfism)

c. Polydactly

d. Sickle Cell

In regard to the presence or absence of anemia,

the HbA allele is dominant. In regard to blood-cell shape,

however, there is incomplete dominance. Finally, as we shall

now see, in regard to hemoglobin itself, there

is codominance.

http://www.csupomona.edu/~biology/bio110/inherit/genes.html

Also Incomplete

Dominance-

Disease

appears under

low oxygen

concentrations

III. Human Genes

A. The human genome is the complete set of geneticinformation

1. Determines characteristics such as eye color and how proteins function within cells

B. From Gene to molecule

1. In both cystic fibrosis and sickle cell anemia, a small change in one amino acid in the DNAof a single gene affects the structure of a protein, causing a serious genetic disorder

Distribution of the sickle

cell trait

Distribution of malaria

http://en.wikipedia.org/wiki/Sickle-cell_disease

Individuals with the

Sickle Cell Allele are

immune to malaria-

RBC’s are destroyed

before the parasite

can reproduce and

infect other cells.

C. Sex Linked Genes

1. REMEMBER… genes on the samechromosome are LINKED together

2. They can be separated during meiosis through CROSSING OVER if they have a little distance between the genes on the same chromosome.

3. Genes located on the sex-chromosomes are said to be sex-linked

a. Many sex-linked genes are found on the X-chromosome

b. The Y-chromosome only contains a few genes

i. Look up Swyer Syndrome

4. Genes carried on the X or Y chromosome are sex linked because they are on the sex chromosomes

a. The X chromosome has many genes that are important for growth and development

b. All X-linked traits are expressed in malesWHY?

i. Males only have 1 copy of the X chromosome (so all x-linked recessive disorders, while females need 2 copies of the defective gene to have the recessive disorder

D. Sex-Linked Gene Disorders

1. Colorblindness

a. 3 human genes associated with color vision are located on the X-chromosome

b. In males, a defectiveversion of any one of these produces colorblindness (1 in 10)

c. Females must receive 2copies of the allele to be colorblind (1 in 100)

X-linked recessive inheritance.

http://www.merck.com/mmpe/sec22/ch327/ch327b.html?qt=symbols&alt=sh

Red—green color blindness

Hemophilia-bleeding disorder

http://adam.about.com/encyclopedia/Color-blindness-tests.htm

http://www.healthofchildren.com/C/Color-Blindness.html

http://www.lancelhoff.com/2007/07/11/color-blindness-test/

http://www.lancelhoff.com/2007/07/11/color-blindness-test/

http://www.lancelhoff.com/2007/07/11/color-blindness-test/

http://www.lancelhoff.com/2007/07/11/color-blindness-test/

http://www.lancelhoff.com/2007/07/11/color-blindness-test/

http://www.lancelhoff.com/2007/07/11/color-blindness-test/

http://www.lancelhoff.com/2007/07/11/color-blindness-test/

A green-red color blind person might see the number 2 while a person with normal vision

could see the number 5.

Simulated Colorblindness

Update…

http://www.color-blindness.com/coblis-color-blindness-simulator/

2. Hemophilia (“bleeders disease”)

a. 2 important genes on the X-chromosomethat code for proteins to help control blood clotting

b. A recessive allele in either of these 2 genes may lead to hemophilia

i. 1 in 10,000 males

ii. Injections of normal clotting proteinsprevent death

X-linked recessive inheritance.

http://www.merck.com/mmpe/sec22/ch327/ch327b.html?qt=symbols&alt=sh

Ex: Familial rickets

Hereditary nephritis

http://dwb.unl.edu/teacher/nsf/c10/c10links/georgia.ncl.ac.uk/VitaminD/vitaminD.html

Ex: Familial rickets

Hereditary nephritis-

autoimmune disease-

inflammation of kidneys

E. X-Chromosome Inactivation

1. Females have 2 X-chromosomes

2. If 1 is enough for males, how does the cell “adjust” to the extra X-chromosome in females?

a. One X-chromosome is randomly switched off

b. Condenses and is called a Barr body

IV. Steps to Solve a Pedigree

A. What is the disorder or condition? Do you know how it is inherited?

1. Autosomal recessive or dominant; sex-linked

B. Make a key if one is not given to you

C. Determine genotypes of unknowns in pedigree

1. List all possible genotypes on pedigree

2. Do a punnett square to check!

D. Answer the questions after you fill-in all genotypes

Chapter 14 Notes: Human Blood Groups

I. Blood Groups

A. Human blood comes in a variety of genetically determined blood groups

1. Using the wrong blood during a blood transfusion can be fatal

Other blood groups (M, N, Duffy, Kell, and Lewis) cause weak or no transfusion reactions, blood is not specifically typed for them unless the person is expected to need several transfusions, in which case the many weak transfusion reactions could have cumulative effects

2. A number of genes help determine blood type but we will focus on two:

a. ABO blood groups

b. Rh blood groups

B. Rh Blood Groups—the easy one first1. The Rh blood group is determined by a

single gene with 2 alleles—positive and negative

2. The positive allele is dominant, so you are Rh positive if your genotype is (Rh+/Rh+) or (Rh+/Rh-)a. Allele Rh+ produces antigens (which are

proteins) on the surface of red blood cells

3. You need two Rh- alleles (Rh-/Rh-) to be Rh negative

4. If mom is homozygous positive for Rh factor and dad is heterozygous for Rh factor, what are the chances they will have a child who is Rh-? (Complete the Punnett Square)

Mother Genotype:

Father Genotype:

Rh+Rh+

Rh+Rh-

Chance of Child being Rh- :

Rh+ Rh+

Rh+

Rh-

Rh+Rh+ Rh+Rh+

Rh+Rh- Rh+Rh-

0%

Hemolytic Disease of the Newborn

Hemolytic disease of the newborn – Rh+

antibodies of a sensitized Rh- mother cross the placenta and attack and destroy the RBCs of an Rh+ baby

http://www.clarian.org/ADAM/doc/PregnancyCenter/14/000203.htm

http://www.tutorvista.com/search/what-is-the-factorization-for-48/page-8/

Rh- mother becomes sensitized when exposure to Rh+ blood causes her body to synthesize Rh+

antibodies

http://nobelprize.org/educational_games/medicine/landsteiner/readmore.html http://www.colorado.edu/intphys/Class/IPHY3430-200/014immune.htm

The drug RhoGAM can prevent the Rh- mother from becoming sensitized

http://www.carolguze.com/text/442-11-clinical_genetics.shtml

Treatment of hemolytic disease of the newborn involves pre-birth transfusions and exchange transfusions after birth

http://health.allrefer.com/health/erythroblastosis-fetalis-intrauterine-transfusion.html

C. ABO Blood Groups Basics

1. This is a case of multiple alleles

2. There are 3 alleles for this gene—A, B, and O.

3. A and B are codominant!

a. O is recessive to A and B

4. Alleles A and B produce antigens (which are carbohydrates) on the surface of red blood cells

a. O produces NO antigens

D. ABO Blood Groups—the wrong blood can be FATAL

1. Antigens are recognized by the immunesystem and induce an immune response

Donor’s cells are attacked by the recipient’s plasma agglutinins causing:

Diminished oxygen-carrying capacity

http://med.mui.ac.ir/slide/immunu/immunu4.html

Clumped cells that impede blood flow

http://www.battleforhealth.com/Battle_for_Health/Agglutination.html

Ruptured RBCs that release free hemoglobin into the bloodstream

Circulating hemoglobin precipitates in the kidneys and causes renal failure (person may die if shutdown is complete-acute renal failure)

http://hmm1019group3.blogspot.com/ http://www.nlm.nih.gov/medlineplus/ency/imagepages/8817.htm

2. If the wrong blood is transfused, the body will respond to these antigens by producing antibodies

a. Antibodies are named for what they attack

3. Antibodies bind to the foreign molecule (the antigen) and blood clumping (Agglutination) will occur, which leads to blood clotting, which leads to death

Testing for

Blood Types

http://biology.clc.uc.edu/courses/bio105/humn_gen.htm

Agglutination Simulation

http://www.nobelprize.org/educational/medicine/bloodtypinggame/game/

E. ABO Blood Groups – What does your Red Blood Cells Look Like?

1. If you have blood type A, then you have:

a. The “A” antigen on the surface or your RBCs

b. You have anti-Bantibodies

c. You can receive type A blood and type Oblood

d. Remember: Your antibodies are named for what they attack—so if you received type AB or type B blood then clumping would occur.

F. Blood Transfusions

1. Type A blood accepts blood from type Ablood or type O blood

2. Type B blood accepts blood from type B or type O

3. Type AB blood accepts blood from type A, type B, type AB, AND type O

4. Type O blood accepts blood from another O

G. Examples

1. What type of blood is this person?

AB+

RBC Compatibility chart

In addition to donating to the same blood group;

type O blood donors can give to A, B and AB;

blood donors of types A and B can give to AB.

2. Which ABO blood type can accept blood from type A, B, AB, or O?

BLOOD TYPE AB!!!

3. Which blood type is the universal acceptor? (include ABO blood type and Rh factor)

BLOOD TYPE AB positive!!!

4. Which ABO blood type can donate blood for a person of type A, B, AB, or O?

BLOOD TYPE O!!!

5. Which blood type is the universal donor? (include ABO blood type and Rh factor)

BLOOD TYPE O negative!!!

6. Human blood type chart:

http://www.vaughns-1-pagers.com/medicine/blood-type.htm

RBC Compatibility

Donor

RecipientO- O+ A- A+ B- B+ AB- AB+

O-

O+

A-

A+

B-

B+

AB-

AB+

II. ABO Blood Groups Crosses

A. Cross a person who’s genotype is AA with a person who is AB.

1. Gametes of Parents = & and &

2. Give the possible genotypes: &

And phenotypes: and

A A A B

A A

A

B

AA AA

AB AB

AA AB

A AB

B. Cross a person who’s genotype is heterozygous A with a person who is O.

1. Gametes of Parents = & and &

2. Give the possible genotypes: &

And phenotypes: and

A O O O

A O

O

O

AO OO

AO OO

AO OO

A O