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