Human Genetics Exam Questions

The pedigree below shows a family in which Tay-Sachs disease has claimed several children.
The individual marked with the arrow has recently been married and seeks genetic counseling to
learn whether this disease may affect any of her prospective children. There is no history of the
disease in her husband's family, although he comes from a similar ethnic background. The
genetic counselor obtains blood samples from the individuals indicated and an RFLP test is run to
determine if there is a risk of Tay-Sachs in any offspring that the couple might have. What should
the counselor tell the family? (MAKE REFERENCE TO THE RFLP RESULTS IN YOUR
ANSWER)

answer: Tay-Sachs disease is autosomal recessive, so a person must be homozygous to have

the disease. The parents of affected individuals must be heterozygous (TSD carriers). #1 (III-2) is
such a person, since she had a TSD child. Her RFLP pattern shows three bands, the expected
pattern for a heterozygote. #2 (III-3) is her brother and has the same pattern. #3 (III-4) is the
sister of #1 and has only the two smaller bands which result from three restriction sites; since this
woman is unaffected, this RFLP allele must be linked to the normal (not TSD) allele. Her
genotype is TT. #4 is the husband of #3 and the father of #6. He has the heterozygous pattern for
the RFLP and is presumably a Tt heterozygote. So is his father (#5, II-10). #6, the proposita, is
homozygous for the RFLP allele linked to normal (she is TT). Her husband, #7, has the
sameRFLP allele as #6; he may also be TT, but we don't know this for certain since no other
information about *his* family is given. However, since #6 is TT, at worst, her children might be
TSD carriers (if the father is a carrier). None of her children should have TSD.

[15 PTS.] V. A. (9) Somatic cell hybridization revolutionized human gene mapping. In a few sentences,
explain why this was
so and why it had been difficult to map genes in humans before the development of somatic cell
hybridization. (Give at least
three reasons why gene mapping in humans was difficult; DO NOT explain the methods involved in
somatic cell
hybridization.)

Somatic cell hybridization allowed genes to be assigned to chromosomes. It had been difficult to do this
(other than for the sex chromosomes) and to find linkages between genes because: humans have small
families, long generation times, no controlled mating, many chromosomes, and a large genome.

(6) B. Briefly explain how mapping genes using somatic cell hybridization differs from conventional
linkage mapping of
genes.
 Somatic cell hybridization involves fusion of human cells and those of another species such as mouse.
The
hybrid selectively loses human chromosomes. By selecting a group of hybrids each containing a different
single human chromosome, it is possible to identify which chromosome contains a gene producing a
particular
protein (eg. enzyme) which can be distinguished from the mouse version. Linkage mapping is based on
recombination frequencies between genes on the same chromosome in crosses where both genes are
heterozygous.

[ANSWERS ARE SHOWN IN BOLD TYPE]

[20 PTS.] I. Fill in the blanks with the information requested. (2 pts. each)

(Nonsense or stop)
codon not specifying an amino acid (do not give the sequence of one)
(Galactosemia)
human disease caused by a defect in carbohydrate metabolism
(tRNA)
molecule having a "connector" role in translation
(VNTR)
type of RFLP having many possible alleles
(Conservative)
mode of DNA synthesis ruled out by results of first round of replication in Meselson-Stahl experiment
(Trisomy)
condition of having three copies of a chromosome (and two of all the others)
(Promoter)
region of DNA containing signals for initiation of transcription
(A=T, C=G)
Give two (2) of the relationships among the bases of DNA which were observed by Chargaff in his
experiments.
(Intron)
region of RNA transcript not specifying amino acids in protein product of a gene
(Cloning)
general term for isolation and manipulation of DNA corresponding to a gene

[12 PTS.] II. Show below is a segment of DNA.

5' TACCGGTAAGACCAA 3'

Draw the complementary strand, including polarity:

3' ATGGCCATTCTGGTT 5'

If the strand shown is the sense strand of a gene draw the mRNA which will be made from this gene,
including polarity:
3' AUGGCCAUUCUGGUU 5'

Using the genetic code table provided, give the protein product of the gene:
The mRNA is read from the 5' end: Leu-Val-Leu-Pro-Val

[12 PTS.] III. Hemophilia is an X-linked recessive trait. For each family listed below, give the genotypes of
the parents and
children, and indicate whether the nondisjunction event responsible occurred in mitosis or meiosis, and if
meiosis, in which
parent and which division:

A. A couple with normal blood clotting (the mother's father was hemophiliac) have a hemophiliac son with
Klinefelter
syndrome

parents' genotypes: Hh female, HY male

child's genotype: hhY (he is XXY)
nondisjunction was in: he had to inherit both h-bearing X's from his mother; nondisjunction in meiosis II
can
produce an egg with the two h-bearing X's

B. A couple with normal clotting have a daughter with Turner syndrome and mild hemophilia

parents' genotypes: Hh female, HY male

child's genotype: hO/hH mosaic
nondisjunction was in: mitosis after fertilization to produce a mosaic

[16 PTS.] IV. In a student lab exercise, four mutants of Neurospora unable to grow on minimal media are
used to illustrate
the principals of biochemical genetics. Each mutant is tested for the ability to grow on minimal if certain
other nutrients are
added. Each nutrient is a precursor to a particular amino acid, lysine. From the information below, draw the
pathway leading
to lysine and indicate the position at which each mutant is blocked.
Mutant
Growth in:
nutrient A
nutrient B
nutrient C
nutrient D
lysine
1
+
-
+
-
+
2
-
-
-
-
+
3
+
+
+
-
+
4
-
-
+
-
+

D --3--> B --1-->A --4--> C --2--> lysine

[12 PTS.] V. The steps listed below are needed for DNA replication or transcription or both.

A. tail addition
B. sealing of nicks
C. primer removal
D. gap filling
E. capping
F. primer synthesis
G. addition of nucleotides to 3' end by polymerase
H. splicing
I. unwinding double helix
J. polymerase binding at promoter

Give the six steps needed in DNA replication (put in order for extra credit):
I, F, G, C, D, B

Give the six steps needed in transcription (put in order for extra credit):
I or J, G, E, A, H

[12 PTS.] VI. A. If a child is born with Down syndrome, why is it important to do karyotypes of the child
and the parents?
(Hint: think about the chances of having a second child with Down's)

If the Down's was due to a translocation, rather than just a sporadic nondisjunction, there is a very high
chance (1 in 3 to 1 in 2) of having a second child with Down's. The parents and child should be tested to
verify the cause of the Down's.

B. A person carrying one copy of a chromosome containing an inversion and one copy of the normal form
of that chromosome is referred to as an inversion heterozygote. Is this person likely to be abnormal? What
are the risks of such a condition?

This person is likely to be normal since they will have the normal dose of all the genes carried on the
inverted chromosome. The risks are reduced fertility and/or abnormal offspring if a crossover occurs
within the inverted region during meiosis in this person. This would result in gametes with duplications or
deficiencies, which are ususally abnormal and inviable.

[16 PTS.] VII. The pedigree below shows a family in which Tay-Sachs disease has claimed several
children. The individual marked with the arrow has recently been married and seeks genetic counseling to
learn whether this disease may affect any of her prospective children. There is no history of the disease in
her husband's family, although he comes from a similar ethnic
background. The genetic counselor obtains blood samples from the individuals indicated and an RFLP test
is run to
determine if there is a risk of Tay-Sachs in any offspring that the couple might have. What should the
counselor tell the
family? (MAKE REFERENCE TO THE RFLP RESULTS IN YOUR ANSWER)

Tay-Sachs disease is autosomal recessive, so a person must be homozygous to have the disease. The
parents
of affected individuals must be heterozygous (TSD carriers). #1 (III-2) is such a person, since she had a
TSD
child. Her RFLP pattern shows three bands, the expected pattern for a heterozygote. #2 (III-3) is her
brother and has the same pattern. #3 (III-4) is the sister of #1 and has only the two smaller bands which
result from three restriction sites; since this woman is unaffected, this RFLP allele must be linked to the
normal (not TSD) allele. Her genotype is TT. #4 is the husband of #3 and the father of #6. He has the
 heterozygous pattern for the RFLP and is presumably a Tt heterozygote. So is his father (#5, II-10). #6,
the
proposita, is homozygous for the RFLP allele linked to normal (she is TT). Her husband, #7, has the
same
RFLP allele as #6; he may also be TT, but we don't know this for certain since no other information
about
*his* family is given. However, since #6 is TT, at worst, her children might be TSD carriers (if the father
is a
carrier). None of her children should have TSD.

Return to BIOL 400 page

BIOL 400: HUMAN GENETICS

Exam #3

November 14, 1994

[ANSWERS ARE SHOWN IN BOLD TYPE]

[30 PTS.] I. For each mutagen below, match the mutagen type, mutation type resulting from, and repair
system capable of
dealing with the damage caused by each agent.

Mutagen
Type of mutagen
Mutation type
Repair system
acridine orange
intercalating agent
frameshift
mismatch
bromouracil
base analog
transition
mismatch
UV
non-ionizing radiation
transition or transversion or
rearrangement
nucleotide excision or
photoreactivation
nitrous acid
base-damaging
transition
base excision
-particles
ionizing radiation
strand break or rearrangement
recombinational
peroxide
strand-breaking
strand break or rearrangement
 recombinational

1. Mutagen type
2. Mutation type
3. Repair system
ionizing radiation
transition
mismatch repair
base analog
transversion
base excision repair
strand-breaking agent
rearrangement
nucleotide excision repair
non-ionizing radiation
frameshift
recombinational repair
bulky agent
strand break
photoreactivation
intercalating agent
base-damaging agent

SOME ANSWERS MAY BE USED MORE THAN ONCE AND THERE MAY BE MORE THAN ONE
CORRECT
ANSWER.

[12 PTS.] II. Many cellular proto-oncogenes have functions in the process of signal transduction, which
involves
communication with and responses to the cell's external environment. List two (2) functions of known
proto-oncogene
products which are part of this process.

growth factors, growth factor receptors, G-proteins, protein kinases, transcription factors

Give two (2) possible mechanisms by which cellular proto-oncogenes may become activated to an
oncogenic (cancerous)
form:

point mutations, fusion to another gene, rearrangements, viral insertion, promoter mutations

[10 PTS.] III. Certain HLA alleles are known to be associated nonrandomly with particular diseases.

---describe the function of the products of HLA genes:

distinction of self and non-self by immune system

--give an hypothesis which could explain this observation:

similarity of HLA product to a foreign antigen resulting in an autoimmune attack OR linkage

disequilibrium
(disease gene linked to HLA locus) OR the HLA protein increases disease susceptibility (eg. by acting as
a
 viral receptor)/

[10 PTS.] IV. Describe at the genetic and molecular level how a carcinogen may cause a cell to become
cancerous. Hint:
refer to what is known about the process leading to colon cancer.

--carcinogens are mutagens

--they may cause mutations in proto-oncogenes and/or tumor suppressor genes
--the accumulation of such changes in several genes may result in the loss of growth control which leads
to
cancer (as is seen in colon cancer, where mutations in several genes must occur before full-blown cancer
results)

[15 PTS.] V. Shown below is a sequence of DNA.

5' ACTAGTTCGGGGGACGTAC 3'

3' TGATCAAGCCCCCTGCATG 5'

Indicate the nucleotides most likely to be damaged or mutated by UV.

the adjacent pyrimidines such as the 5' TT 3' in the top strand and the 5' TCCCCC 3' in the bottom strand

Indicate the nucleotides most likely to be involved in a frameshift mutation.

the run of 5 G:C base pairs could "slip" and mispair leading to a frameshift

Indicate the nucleotides most likely to be mutated by deamination in a human cell.

the C's of the 5' CpG 3' sequences in each strand--if the C's are methylated, they can deaminate to T and
cause a mutation

[10 PTS.] VI. Explain the genetic and immunological basis of hemolytic disease of the newborn.

this occurs when the genotype of the mother is rr (Rh-) and the genotype of the fetus she carries is Rr
(Rh+)

the immunological basis is that such a woman in a first pregnancy with an Rh+ child will be exposed to
Rh+
cells at birth when the maternal and fetal circulation can mix; at this time she will mount an immune
response to the Rh+ antigen. This can also occur if she has been exposed to Rh+ blood cells in a
transfusion.
In the next pregnancy with an Rh+ child, the anti-Rh antibodies of the mother cross the placenta and
attack
the fetal blood cells, producing a serious disease in the developing fetus

[5 PTS.] VII. Given that the purpose of DNA repair systems is to maintain the sequence of DNA and avoid
changes in the
sequence, under what circumstances might an error-prone or mutagenic repair system be used by a cell?

--when other repair systems are nonfunctional (ie. in a mutant)

--when so much damage has occured that not all of it can be repaired accurately (eg., overlapping
damage)

I. A. (5 pts) Which of the following statements regarding heritability is NOT true?

1) It is specific to the population being studied.
2) It is the fraction of phenotypic variance of a trait which is due to genetic differences.
3) It can be estimated from twin studies.
4) It is the degree to which a trait is determined by genes.
5) It applies to groups rather than individuals.

#4 is not true.

B. (18 pts) Shown below are concordance values for three traits in monozygotic (identical ) and dizygotic
(fraternal) twins.

(9) Which trait has the greatest heritability? Why?

Epilepsy. Because the difference between MZ and DZ is large and MZ concordance is high. Or, you could
calculate
heritability using the formula H = [%MZ - %DZ]/[100 - %DZ]. This gives H values of 0.67, 0.30, and 0.25,
respectively, for the traits epilepsy, club foot, and age at first sitting up.

(9) In which case(s) are environmental factors likely to be important?

Club foot, since although the MZ concordance is greater than the DZ concordance, both are much less than
100%,
implying significant environmental influence. Also, for sitting up, concordance values are high in both
types of twins,
suggesting that the genetic identity shared by MZ twins is not as important as the environment.

II. (27 pts)

A. (9) Calculate the frequency of heterozygotes (Aa) in a random-mating population in which the
frequency of all dominant
genotypes (ie. the dominant phenotype) is 0.19. (Assume that there are only two alleles, A and a, and that A
is dominant.)
SHOW YOUR WORK.

The genotypes are AA, Aa and aa; their equilibrium frequencies given by the Hardy-Weinberg equation are
p-squared, 2pq, and q-squared, respectively. The dominant genotypes AA and Aa account for 0.19 of the
population,
implying that aa genotypes are in a frequency of 0.81. Thus q is the square root of 0.81, or 0.9. p = 1 - q =
0.1. The
frequency of heterozygotes is 2pq, or (2)(0.1)(0.9) = 0.18.

B. (9) In a particular population, the relative fitness of the genotypes AA, Aa and aa were determined to be
0.9, 1.0, and 0.7,
respectively. Assuming that only selection is operating on these genotypes, calculate the equilibrium
frequencies of A and a
in this population. SHOW YOUR WORK.

In selection against both heterozygotes there are two selection coefficients, s and t. The fitness of a
genotype is one
minus the selection coefficient. Thus the selection coefficient against the AA genotype is 1 - 0.9 or s = 0.1.
The
selection coefficient against the aa genotype is 1 - 0.7 or t = 0.3. The equilibrium frequencies are
determined by the
selection coefficients: p, the equilibrium frequency of A, is t/[s + t]; 0.3/[0.1 = 0.3] = 0.75; q, the
equilibrium frequency
of a, is s/[s + t]; 0.1/[0.1 + 0.3] = 0.25.
C. (9) The Dunkers are a religious sect that originated in the Rhineland region of Germany and settled in
Pennsylvania during
the 18th century. Since that time, the sect has remained relatively isolated from the surrounding population
both in custom and
mating. The table below shows the frequency of ABO blood types in the Dunkers, in the surrounding
American population,
and in the present-day Rhineland German population.

Population
No. tested
A
AB
B
O
Dunkers
228
0.593
0.022
0.030
0.355
Rhineland Germans
5036
0.446
0.047
0.100
0.407
Eastern USA
30000
0.395
0.041
0.112
0.452

What explanation would you offer to account for the blood-group frequencies among the Dunkers?

Since the Dunkers are a small, isolated population, genetic drift is the most likely cause of their present
blood group
frequencies, particularly since these are not intermediate between the US and German values, but are the
extreme. A
founder effect may also be operating here.

III. (12 pts.) We discussed in class a number of situations in which prenatal screening by amniocentesis or
chorionic villus
biopsy would be performed. List four of these situations.

advanced maternal age; previous child with biochemical defect, neural tube defect, and/or chromosome
abnormality;
two or more previous miscarriages; chromosome abnormality in either parent; mother carrier of sex-linked
recessive
disease; both parents carriers of autosomal recessive disease; fetal or parental exposure to
carcinogens/mutagens/teratogens.

IV. (16 pts.) Describe one of the methods of artificial parenthood that were given in the text and in lecture.
Indicate: 1) in
what situation(s) it would be used; 2) any potential moral, ethical, or legal problems associated with its use.

Methods are artificial insemination, surrogate motherhood, and in vitro fertilization; answer had to include
description
of methods and technqiues and answers to questions 1 and 2