Download GENETIC DISORDERS AND PEDIGREES

BIOL 117 HYBRID
GENETIC DISORDERS
03/24/2016
See BB for websites to access before doing this assignment!!!
Topics
I. Autosomal Single Gene Disorders.
A. Autosomal Recessive Traits.
B. Autosomal Dominant Traits.
-Worksheet
II. Sex-linked Disorders.
-Worksheet
III. Pedigrees.
-Worksheet
You must do these problems BY HAND. ALL WORK IS REQUIRED. When completed,
bring the worksheets to the instructor’s office. Only turn in the worksheets.
Remember to put your name on ALL PAGES OF the worksheets.
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Terms
1. Autosome: Any chromosome other than the sex chromosomes (X & Y). Chromosome
designated 1-22.
2. Sex chromosome: X or Y.
3. Allele: Alternate forms of the same gene.
4. Dominant: Trait will be expressed if one allele is present.
5. Recessive: Trait will be expressed only if two alleles are present (one from each parent).
6. Homozygous: Having two copies of the same allele for a particular gene.
7. Heterozygous: Having two different alleles for a particular gene.
8. Carrier: Person with only one copy of the disorder allele.
9. Genotype: Actual alleles a person inherited from the mother and father
10. Phenotype: Outward expression of the trait.
11. Punnett Square: A grid used to determine potential genotypes and phenotypes of offspring by
combining the parents’ gametes.
Allele Symbols:
Possible Genotypes:
Autosomal dominant: H (capital letter is dominant)
HH
Hh
hh
Autosomal recessive: h (lowercase)
Sex-linked: Xc
A gene on the X chromosome (X-linked)
XC XC
XC Xc
Xc Xc
XCY
XcY
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I. Autosomal Single Gene Disorders
Thousands of autosomal, single gene disorders have been clinically characterized. They are
caused by too much, too little, or abnormal proteins.
A. Autosomal Recessive
Examples of Disorders
1. Adenosine Deaminase Deficiency (ADA): one form of SCID, “bubble boy” disease
(chromosome 20).
a. Enzyme missing which is necessary for the immune system=s T cells to
function.
b. Results in lack of immunity = frequent, severe infections.
c. First hereditary condition treated with gene therapy (1990).
2. Tay-Sachs Disease (chromosome 15)
a. Progressive nervous system degeneration.
b. A child is deaf and blind by one or two years- progressive mental retardation,
loss of muscular control; usually die at age three or four.
c. Caused by a mutation of the HEXA gene, which normally codes for the enzyme
hexosaminidase A (necessary for proper nerve function).
d. Rare in U.S. because predominant populations are screened for carriers; most
carriers choose to avoid the birth of a child because there is no treatment.
e. Common in French Canadians, certain Jewish populations, Pennsylvania
Dutch, and Cajuns.
3. Cystic Fibrosis, CF (chromosome 7)
a. The most common genetic disorder among Caucasians. About 1 in 25
Caucasians are estimated to be carriers. It is rare in African Americans and
Asians. It affects about 30,000 children and adults in the U.S.
b. Deficiency of the protein cystic fibrosis transmembrane conductance regulator
(CFTR). This protein is found in the membrane of cells. The normal function of
this protein is to transport chlorine across the cell membrane. The dysfunctional
gene results in abnormal salt transport across membranes.
c. Symptoms: salty sweat, increased mucus secretion in various ducts and tracts;
pancreatic, liver, pulmonary, and digestive dysfunction; frequent severe
infections; usually infertile; symptoms become more severe with age.
d. With present management (hitting the chest to clear infected secretions that
accumulate in the lungs, taking replacement enzymes, and antibiotics to treat
infections), average life expectancy is 40+ years.
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Determining the chances of passing on the allele and disorder.
Possible genotypes:
Phenotype
No cystic fibrosis
CC
No cystic fibrosis; but can pass on the allele to
the offspring (carrier).
Cc
Cystic fibrosis
cc
Autosomal Recessive: Parents do not have to be affected to have an affected child; often skips
generations.
Example Problem 1: One carrier parent and one homozygous recessive parent.
Cc x cc
Cc
Possible
Gametes:
C or c
cc
c
Use a punnett square to determine all possible offspring genotypes and phenotypes and
their frequency probabilities.
See next page for example punnett square.
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These are all possible eggs.
c
C
Cc
c
cc
These are all
possible offspring
genotypes.
50% Cc, 50% cc
These are all possible
sperm.
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Example Problem 2: Two carrier parents.
Cc x cc
Cc
Possible
Gametes:
Cc
C or c
C or c
Use a punnett square to determine all possible offspring genotypes and phenotypes and
their frequency probabilities.
See below for example punnett square.
These are all possible eggs.
C
c
C
c
These are all possible
offspring genotypes.
CC
Cc
25% CC (no cystic fibrosis)
Cc
50% Cc (no cystic fibrosis,
but a carrier)
cc
25% (cystic fibrosis)
These are all possible
sperm.
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B. Autosomal Dominant
Examples of Disorders
1. Huntington disease (chromosome 4)
a. Caused by an abnormal protein (huntingtin) whose exact normal function is
unknown.
b. Progressive nerve degeneration.
c. Usually adult onset (35-45 years) of symptoms.
d. Worsening gait, constant uncontrollable movements, personality changes...
e. Death usually within 10-15 years after diagnosis.
2. Amyotrophic lateral sclerosis (ALS, Lou Gehrig’s disease) (chromosome 21)
a. Affects 1 in 100,000 people worldwide, but only 10% of the cases are inherited.
The other 90% are probably environmentally induced (don’t know cause).
b. Fatal degenerative nerve disease.
c. Stiffening and weakening of the legs and arms, become quadriplegic, die as
respiratory muscles become paralyzed.
d. Mutation in the gene for the enzyme superoxide dismutase, an anti-oxidant that
detoxifies molecules (free-radicals) that damage tissue.
3. Achondroplasia: A form of dwarfism (chromosome 4)
4. Familial hypercholesterolemia (chromosome 19)
-This is one type of incomplete dominance.
-hh:
-Hh:
Have normal amounts of molecules which remove cholesterol from
the blood
Have half the normal number of molecules that remove cholesterol
from the blood; therefore, cholesterol builds up along the walls of
the arteries. Affected individuals can affect lifespan by monitoring diet
(Example: decreasing amount of cholesterol in diet can extend life).
-HH: Have very few molecules that remove cholesterol from the blood; usually
die at a very young age of heart attack or stroke.
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Determining the chances of passing on the allele and disorder.
For autosomal dominant traits, only ONE copy of the mutated allele is required for an individual
to be affected, and this can be inherited from either parent. Individuals with a dominant trait have
a 1 in 2 chance of passing that allele, and, therefore, that trait, to each of their children. If a child
is affected, one parent must be affected.
Example: Heterozygous mother and unaffected father
hh x Hh
Possible
Gametes:
hh
Hh
h
H or h
Use a punnett square to determine all possible offspring genotypes and phenotypes and
their frequency probabilities.
See below for punnett square.
These are all possible eggs.
H
h
These are all possible
sperm.
Hh
h
hh
These are all
possible offspring
genotypes.
50% Hh, 50% hh
Therefore,
Predict that 50% of
offspring would be
affected by the
dominant trait and
50% would not be
affected.
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Name:
BIOL 117 Hybrid
Worksheet: Genetics Problems – Autosomal Traits
STEPS IN SOLVING GENETICS PROBLEMS:
1. Write down all of the known information:
A. Dominant and recessive traits and symbols
B. Phenotypes and genotypes of parents
C. All possible gamete genotypes
D. Set up a punnett square
E. Determine genotypes and phenotypes of offspring
2. Be sure to carefully determine and, IF NECESSARY, ANSWER IN WORDS, the
exact question being asked.
Complete the following problems on this page.
Follow ALL of the steps above.
YOU MUST SHOW ALL WORK. Points will be deducted for not showing work.
1. Freckles are an autosomal dominant trait. A woman with freckles (Ff) marries a man without
freckles. What are the chances that their children will have freckles? (Answer in percentages).
2. Two freckled adults marry and have children. The first baby has no freckles. What are the
genotypes of the parents?
3. In humans, normal pigmentation is due to a dominant gene A. Albinism is due to the
recessive allele a. A man without albinism marries an albino woman and their first child is an
albino. What are the genotypes of these 3 people?
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II. Sex-linked Disorders
Sex-linked disorders can be on either the X or Y chromosome. Since the X chromosome is
larger and contains more genes, most sex-linked disorders are found on the X chromosome.
Many are recessive. Y-linked genes also have been identified.
X-linked disorders
One form of bipolar affective disorder is
recessive X-linked (another form is
autosomal recessive).
Hemophelia
Red-green color blindness
Duchene muscular dystrophy
See Allele Symbols on page 2.
Y-linked Disorders (Y only, no
homologous gene on X)
Several genes affect fertility and sex organ
development. One gene called DAZ, if
missing from the Y chromosome or
mutated, will result in a low sperm count.
SRY gene (testes determining)
Hairy ears?
Example: Recessive X-linked trait. Carrier mother and Unaffected father
XHXh x XHY
See punnett square below.
Possible
Gametes:
Predict that 0% of female and 50% of
male offspring would be affected by
the trait and would be affected.
XHY
XHXh
XH or Y
XH or
Xh
Punnett Square:
These are all possible eggs.
XH
These are all possible
sperm.
Xh
XH
XH XH
XH Xh
Y
XHY
XhY
These are all
possible offspring
genotypes.
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Name:
BIOL 117 Hybrid
Worksheet: Genetics Problems – Sex-linked Traits
STEPS IN SOLVING GENETICS PROBLEMS:
1. Write down all of the known information:
A. Dominant and recessive traits and symbols
B. Phenotypes and genotypes of parents
C. All possible gamete genotypes
D. Set up a punnett square
E. Determine genotypes and phenotypes of offspring
2. Be sure to carefully determine and, IF NECESSARY, ANSWER IN WORDS, the
exact question being asked.
Complete the following problems on the next page. Follow ALL of the steps above.
YOU MUST SHOW ALL WORK. Points will be deducted for not showing work.
1. In humans, red-green color-blindness is due to a recessive gene Xc. Normal vision results
from the dominant gene XC. If a homozygous woman of normal vision marries a color-blind
man, what type of vision will be expected in their children?
2. A X-linked gene in cats controls coat color. The XB allele produces black, and the Xb allele
produces yellow. When heterozygous (XB Xb), the coat color is calico. If a yellow female cat
has one yellow kitten and three calico kittens, 1) What is the sex of the yellow kitten? 2) What is
the color of the father of these kittens? 3) What does this tell you about the sex of any calico
cat?
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III. Pedigree: A diagram of a family history showing the occurrence of a trait
Pedigrees are helpful in determining whether a trait has a genetic component, and, if so, the
pattern of inheritance (autosomal recessive, autosomal dominant, or sex-linked recessive).
Go through this animation: http://dnalc.org/view/15913-The-pedigree.html
Symbols are used in the diagram:
Vertical line: Parents
leading to children
Affected female
Affected male
Horizontal lines connect
parents or siblings
Unaffected male
Unaffected female
Deceased female (affected by that trait and
male (unaffected by the trait in question)
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Clues to Pedigree Problems
A. When determining if a trait is sex-linked or autosomal…
1. An X-linked trait is usually expressed far greater in males since most are Xlinked recessive. If X-linked, we will only consider X-linked recessive traits
(none will be X-linked dominant).
2. Y-linked traits are only passed from father to son. Females are never affected.
In this assignment, none of the traits are Y-linked.
3. An autosomal trait is expressed approximately equally in males and females.
B. When determining if an autosomal trait is dominant or recessive…
1. Dominant traits only require one allele to outwardly express the trait.
a. Dominant traits are often present in every generation.
b. If a child is affected, at least one parent must be affected.
2. Recessive traits require two alleles to outwardly express the trait.
a. Recessive traits often skip generations.
b. An affected child does not have to have an affected parent.
C. When attempting to determine the pattern of inheritance, scan the pedigree. Use the
above clues to make an educated guess as to the most likely pattern of inheritance.
D. Use a PENCIL to write in the genotypes according to the pattern of inheritance
you've chosen. If the genotype of the second allele is unknown, put a ? by the first
allele.Continue writing in genotypes until an individual doesn't "fit". If one doesn't "fit",
erase all of the genotypes, and try another pattern of inheritance using new genotypes.
Rule out each pattern of inheritance. It is a matter of exclusion.
Occasionally, with the limited information available, more than one pattern of inheritance
may be included as ‘possible’.
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Queen Victoria of England was a carrier of the gene
for hemophilia. She passed the harmful allele for
this X-linked trait on to one of her four sons and at
least two of her five daughters. Her son Leopold had
the disease and died at age 30, while her daughters
were only carriers. As a result of marrying into other
European royal families, the princesses Alice and
Beatrice spread hemophilia to Russia, Germany, and
Spain. By the early 20th century, ten of Victoria's
descendents had hemophilia. All of them were men.
Queen Victoria
(1819-1901)
It is assumed that a chance mutation in either the egg or sperm that came together to make Queen
Victoria caused her to unknowingly be a carrier for the hemophilia allele (XX'). When she grew up,
she married Prince Albert, who was normal XY. One would predict that ½ of their sons (¼ of their
children) would be hemophiliacs and ½ of their daughters (¼ of their children) would be carriers.
Their children married other royalty, and spread the gene throughout the royal families of
Europe.
Carriers in the above pedigree have a half circle filled in.
Try this animation out to test your understanding http://dnalc.org/view/16323-Problem-13Mendelian-laws-apply-to-human-beings-.html
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EXAMPLE
ASSUME ALL SEX-LINKED ARE X-LINKED (NOT Y) AND ARE RECESSIVE.
Possible Patterns of Inheritance:
1. Autosomal Dominant, or 2. Autosomal Recessive, or 3. X-linked recessive
I. Determine the pattern of inheritance in the following pedigrees. Write correct genotypes for
all of the individuals. If the genotype of the second allele is unknown, put a ? by the first allele.
Letter Symbols with respective traits: H= not affected
h= affected
H?
hh
1. Use the clues on page 13 to make an educated guess
as to the pattern of inheritance. Here, autosomal
recessive was our first ‘educated guess’ since it was
not found in every generation (Parents did not have to
be affected for offspring to be affected).
Hh
Hh
hh
Hh
H?
Hh
Hh
hh
Hh
Hh
H?
hh
hh
3. EVERY individual’s genotype (HH, Hh, hh or H?) is
PENCILED in by each individual’s symbol. In this case,
autosomal recessive ‘fit’ all of the individuals.
H?
2. A letter was then chosen to
represent dominant and recessive
alleles. If the trait is autosomal
recessive, affected individuals
(with darkened symbols) would
have to be hh. Since the
dominant trait only requires one
allele to be expressed, you may
not know if the second allele is
dominant or recessive. In that
case, I put a ‘?’ by the dominant
allele.
Correct pattern of inheritance: Autosomal Recessive OR (see next page!)
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EXAMPLE
X-LINKED RECESSIVE!
X HX ?
XhY
If you try sex-linked (X-linked recessive), you
would find that this pattern of inheritance also fits.
In this case, X-linked recessive may be the better
choice since only males are affected.
X HY
X HY
XhY
X HX h
X HX h
X HX h
X HY
Xh Y
X HX h
X HX ?
X HY
XhY
XhY
X HY
Remember to use the correct symbols when penciling in the genotypes over every person. Only
sex-linked traits use X and Y symbols. Autosomal traits do not use X and Y, as the example on
the previous page illustrates.
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Name:
BIOL 117 Hybrid
Worksheet: Pedigrees
Pedigree 1. Use H or h for the letter symbols of the alleles (or XH and Xh if sex-linked).
1. Using the clues, make an educated guess as to the correct pattern of inheritance (autosomal
recessive, or autosomal dominant, or sex-linked recessive)
2. Pencil in genotypes for all individuals. Remember to use a ? if an allele is unknown.
3. If this pattern of inheritance ‘fits’, write the correct pattern at the bottom of the page. If it did
not fit, erase the genotypes and try another pattern until you find one that does fit.
Write the correct pattern of inheritance (autosomal recessive, or autosomal dominant, or sexlinked recessive)
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Pedigree 2. Use H or h for the letter symbols of the alleles (or XH and Xh if sex-linked).
1. Using the clues, make an educated guess as to the correct pattern of inheritance (autosomal
recessive, or autosomal dominant, or sex-linked recessive)
2. Pencil in genotypes for all individuals. Remember to use a ? if an allele is unknown.
3. If this pattern of inheritance ‘fits’, write the correct pattern at the bottom of the page. If it did
not fit, erase the genotypes and try another pattern until you find one that does fit.
Write the correct pattern of inheritance (autosomal recessive, or autosomal dominant, or sexlinked recessive)
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Pedigree 3. Use H or h for the letter symbols of the alleles (or XH and Xh if sex-linked).
1. Using the clues, make an educated guess as to the correct pattern of inheritance (autosomal
recessive, or autosomal dominant, or sex-linked recessive)
2. Pencil in genotypes for all individuals. Remember to use a ? if an allele is unknown.
3. If this pattern of inheritance ‘fits’, write the correct pattern at the bottom of the page. If it did
not fit, erase the genotypes and try another pattern until you find one that does fit.
Write the correct pattern of inheritance (autosomal recessive, or autosomal dominant, or sexlinked recessive)
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