Lecture Objectives of Genetics Exam 2
Lecture 11: Human Chromosome
1. Define the following terms relating to chromosome morphology:
a. Sister chromatids
i. A chromosome in a haploid n-2 c-1 cell. Both are identical
b. Centromere
i. The central region of a chromosome that has a large amount of
repetitive DNA so that it can be recognized on the other region of
the the sister chromatid.
c. p arm
i. Short arm on one side of the centromere
d. q arm
i. Larger arm on the other side of the centromere
e. telomere
i. The repetitive sequence at the end of the chromosome that
prevents gene loss through buffering the end of replication typicial
telomerase can only under go 50 to 60 replications, tumor cells are
unlimited. (fail safe)
f. kinetochore
i. The protein complex that binds the centromeric region to the
tubules on the spindle complex. Contain motor proteins that allow
for movement of the chromosomes
2. Define homologs. Describe genes and alleles in relationship to homologs.
a. Homologs are a matching chromosome pair but have different origins.
One is maternal and one is paternal. They have the same gene locations
but different alleles reside there that code for differing phenotypes. Ex of
eye color.
3. Define autosomes and sex chromosomes, gametes and somatic cells.
Describe the chromosomal basis of gender determination in humans.
a. Autosomes are the non sex chromosomes 1-22 pairs, and sex
chromosomes are the X and Y. Chromosomal basis is the determination of
whether or not a person has a Y or 2 X’s. Gametes are the germ cells that
only have a haploid n-1 c-1 cell. One set of chromosomes that have only
23 chromosomes, think half of a sister chromatid pair. Somatic cells have
46 chromosomes or 23 pairs. Gametes only have 23 chromosomes, no
pairing, this is how sex is determined, because in meiosis the sex
chromosomes are separated in division so a guy can have a Gametic cell
that contains an X or a Y not both.
4. Define and distinguish the characteristics by which chromosomes are classified.
Be certain to use the following terms:
a. Metacentric
i. An even division of the p and q arm where the centromere is
located evenly in the middle of the chromosome.
b. Submetacentric
i. An uneven division of the chromosome where the p arm is shorter
and the q arm is larger
c. Acrocentric
i. The centromere is located at the end of the chromosome but not in
the telomere region.
d. Telocentric
i. The centromere is located in the telomeric region.
5. Define the significance of mitosis and differentiate the phases and the significant
events in each phase.
a. Mitosis allows for exact replication of a somatic cell so that the number of
chromosomes and nuclei stay the same with an even distribution of
cytoplasm and proteins. Produces 2 daughter cells.
b. Phasesi. S
1. Synthesis, doubling of the DNA,
ii. G2
1. Error checking, p54 checking protein, proto-oncogenic
signal.
iii. M
1. Mitosis, separation of the cells and the cytoplasm
iv. G1
1. If more replication is need the cell will enter G1 and double
it’s contents except DNA for replication
v. G0
1. The cell will enter this phase is no more replication is
needed, typical nerve cell.
c. Phases of mitosis- take a total of 1-2 hours, why? All that genetic
information is needed to sustain the cell and it is unusable when it is
condensed into visible chromosomes.
i. Prometaphase (prophase)
1. Dissolution of the nuclear membrane, formation of the
centrioles and attachment of the spindle fibers to the
kinetochores, condensation of chromosomes into sister
chromatids.
ii. Metaphase
1. Alignment of the sister chromatids on the metaphasic plate,
chromatids begin to separate but stay attached at the
centromere region.
iii. Anaphase
1. Breaking at the centromeres occur and seperation of the
chromatids to the poles occur
iv. Telophase
1. Later in the seperation when the chromatids have reached
the pole and start to reform the nuclear membrane
v. Cytokinesis
1. Cytoplasm is divided, cleavage furrow begins to form allow
dynamin to pinch the two cells in half.
6. Define the significance of meiosis and differentiate the phases and significant
events in each phase including the sub-phases of prophase I.
a. Meiosis allows for gamete formation, and differs from mitosis in 3 aspects
b. Meiosis occurs during formation of gametes
c. Meiosis has 2 steps- reduction of tetrads to chromosome homologous
(maternal and paternal chromosomes double then join together in the
first step, and then they divide into haploid cells for meiosis 2.)
d. Mitosis keeps the daughter cells in the diploid state after the first division,
chromosome pairs.
e. Prophase 1- 5 stages
i. Leptotene - Condensed chromosomes become visible (just finished
G2) start to form axial elements
ii. Zygotene - axial elements are completed and align on the
synaptonemal complex
iii. Pachytene - Synaptonemal complex is formed and the cross over
occurs, with bivalent cross over forming chiasmate
iv. Diplotene - separation starts to occur but the chiasmata are still
attached, can have up to 3 cross overs per chromosome.
v. Diakinesis - continued separation of the chromosomes.
vi. Metaphase 1- tetrads align on the metaphasic plate
vii. Anaphase 1- tetrads are pulled apart and start to move towards
there respective poles
viii. Telophase 1 – reformation of a nuclear membrane and now have a
haploid set of chromosomes.
f. The second phase of meiosis is the same as mitosis except you are
separating homologous chromosomes in a haploid cell into chromatids so
that the gamete has the equivalent of only 23 chromosomes and 1 sex
chromosome either X or Y
7. Define crossing over including its effect on the alleles located on homologous
chromosomes
a. Crossing over is the reshuffling of genes between homolgous parental
chromosomes. This allows a gene region in a maternal chromosome that
correlates with a gene region on the parental chromosome to switch, this
allows for allelic switches between chromosomes in the same gene
region. No genetic information is lost but merely switch from one
chromosome to another that is homologous to it.
Lectures 12 and 13- Chromosomal Disorders
1. Differentiate the steps of the procedure by which human chromosomes are
obtained for study.
a. Culture WBC with PHA for division
b. Add colchicine which blocks formation of the spindle fibers
c. Stopped during metaphase when most visible
d. Cells are placed in hypotonic solution and they swell up
e. Dropped onto a slide and allowed to lyse
f. Metaphasic chromosomes are then stained and observed.
2. Describe the reason for banding chromosomes and state the four most common
banding procedures.
a. Banding of a chromosome allows for identification of a chromosome
number (whether it is 1, 4 , ect). And look for the large deletions.
b. G-banding
i. most frequently used banding technique in cytogenic laboratories,
uses trypsin then stains with Geimsa, which stains dark bands
correlating with repetitive DNA sequences
c. Q-banding-(Quinacridine Banding)
ii. First banding technique discovered, AT pairs fluoresce and GC
pairs suppress the fluorescence
d. R-banding-(Reverse banding)
iii. Is the reversal of the G staining regions in G banding
e. C-banding
iv. Target satellite sequences and heterochromatin
3. Define karyotype and idiotype. Explain when a karyotype would be ordered in
clinical practice.
a. Karyotype- it is a set of chromosomes obtained from a person who’s cells
were stopped in metaphase and then stained. They were paired and
placed in order
b. Idiotype- it is an idealized karyotype, one that is recreated from an
original picture so there is clearer contrast
4. Contrast/compare aneuploidy and polyploidy.
a. A numerical abnormality is an aneuploidy where a polyploidy is gain of a
whole other set of haploid chromosomes. Aneuploidy would be the gain
of a single haploid chromosome where as polyploidy would be the gain of
another full set of haploid chromosomes, going from 23 pairs of
chromosomes and a pair of sex chromosomes to 46 autosomal
chromosomes and 3 sex chromosomes.
5. Using the proper nomenclature, define the most common aneuploid conditions.
a. Monosomy
i. Turner’s syndrome is the monosomy of sex chromosomeautosomal monosomies are always lethal. Notation for Turner’s 45
X
b. Trisomy
ii. Down’s syndrome-trisomy 21, written 47 XY +21
iii. Patau’s syndrome- trisomy 13 written 47 XY +13
iv. Edward’s syndrome- trisomy 18 written 47 XY +18
6. Describe mitotic and meiotic nondisjunction and the effects of each.
a. Meiotic nondisjunction
i. Level 1
1. Results in 2 haploid gametes and 2 nullisomoy gametes.
ii. Level 2 nondisjunction
1. Results in 2 monosomy gametes and 1 hapliod and one
nullisomy
iii. Meiotic nondisjunction results from an issue in the spindle
formation or an issue in the crossover junction the chiasmata. This
will have serious repercussions if the sperm or ova is used in
fertilization. Extra or missing genetic information usually has a
lethal affect on the fetus.
b. Mitotic nondisjunction
i. This occurs in somatic cells and usually does not have a lethal
effect and it cannot be passed on to another generation.
7. Distinguish between the following chromosomal aberrations:
a. Reciprocal translocation
i. A balanced exchange where all genetic material is preserved
(exchange between 11 and 22 is common)
b. Non-reciprocal translocations
i. The genetic material is moved from one chromosome but no new
information is reciprocated back to the donating chromosome.
c. Robertsonian translocation
i. A break occurs near the centromere of 2 acrocentric chromosomes
and the q arms join but the p arms form a small fragment where it
is usually lost in segregation.
d. Insertion
i. 1 segment of a chromosome is inserted into another chromosome
if it is copied and inserted into another chromosome then the
karyotype stays balances, but if it is lost in the donating
chromosome then you have an unbalanced karyotype
e. Deletion
i. Loss of genetic information from a chromosome, at that region the
person is monogenic (the other chromosome of the pair has the
needed allele) if the deletion is greater than 2% of the
chromosome then it is lethal. Large deletions are seen in
microscopes in banded karyotypes (Cru de chat and WH
syndrome) but small deletions can be seen in FISH testing
(Angelman and Prader Willie syndrome)
f. Paracentric inversions
i. An inversion not involving the centromere
g. Pericentric inversions
i. An inversion involving a centromere
h. Ring chromosome
i. Where there is a break at the end of both of the chromosome
which results in them sticking together and forming a ring.
i. Isochromosome
i. Formation of a chromosome of with 2 q arms and a chromosome
of 2 p arms. There is a break transversely rather than
longitudinally.
8. Summarize the potential complications, if any, that may occur at mitosis and/or
meiosis for each aberration.
a. Reciprocal translocation
i. Causes a quadrivalent chromosome structure on the metaphase
plate and if the alternate chromosomes segregate with each other
then the karyotype will be balanced, but if the adjacent segregate
then the karytype will not be balanced. These can form a 2:2
chromosome seperation or a 3:1 segregation because of the
homologous regions between the 3 chromosomes; cause one to
drag an extra chromosome along into the gamete. 3:1 segregation
cause trisomic material to be transferred.
b. Non-reciprocal translocation
i. Unbalanced genetic material causes unbalanced segregation
because 1 chromosome will have lost information and 1 will have
extra information. Unless the 2 chromosomes segregate together
which will allow for the lacking genetic information to be joined
together.
c. Robertsonian translocation
i. Form a trivalent in metaphase, if split alternatively then the
segregation will be balanced, if the split is adjacent then
monosomy and trisomy will occur.
d. Insertion
i. If the insertion was removed from one chromosome and placed
into another chromosome then there will be an unbalanced
karyotype but if the insertion was copied from one chromosome
without being deleted and placed into another chromosome then
the segregation will be balanced. Both types are at a 50% risk of
producing unbalanced haploid gametes.
e. Deletion
i. Results in loss of genetic information for about 50% of the
gametes.
f. Pericentric inversion
i. During meiosis it forms a normal gamete, and inverted gamete and
2 gametes with a duplicated segment and a deleted segment.
Essential make a U of the two chromosomes with there segments
and you will create the two deleted gametes.
g. Paracentric inversion
i. Creates products in meiosis that are dicentric or acrocentric in
which case then the zygote with these mutations will not survive.
h. Isochromosome
i. Can result in partial trisomy and monosomy, can cause Turner’s
syndrome (loss of the X chromosome in females)
i. Ring chromosome
i. When the ring formation is made by the two sticky ends coming
together, it is an unstable form in mitosis and is not passed on to
the somatic daughter cell causing monosomy.
9. Define chimerism and differentiate between the two most common
causes/forms.
a. Chimerism
i. Presence in an individual of two or more distinct cell lines, with
different genetic origins.
b. Dispermic chimerism
i. 2 sperm fertilize 2 eggs then during development (blastomere)
they fuse into 1 person or embryo and make a fetus that is 50/50
of genetic lines.
c. Different sex embryos
i. When 2 blastomeres fuse that have different sex chromosomes a
true hermaphrodite is forms.
d. Blood chimera
i. When twins share blood in utero they develop immunity to the
other blood type.
10. Distinguish between the various forms of FISH and their uses in the diagnosis of
chromosomal disorders
a. Centromeric probes
i. Bind to centromere regions and is a quick diagnostic measure of
anueploidy, trisomy 21, 18, and 13.
b. Chromosome-specific unique sequence probes
i. There are specific to a single locus and are helpful in finding
specific deletions or microdeletion syndromes. They can bind
c. Telomeric probes
i. Helpful in translocations of chromosome sections, like Burkitts
lymphoma.
d. Whole chromosome paint probes
i. It is a cocktail of multiple probes from one chromosome and paint
the whole chromosome for picking out complex rearrangments
and subtle translocations.
Lecture Objectives of Lecture 14: Mendelian Inheritance
1. Define the following basic genetics terms:
a. Dominant allele
i. Only one copy of the gene is need for expression
b. Recessive allele
i. Both copies of the gene is needed for expression
c. Phenotype
i. Observable expression of a genotype in a biochemical,
morphological characteristic or clinical trait.
d. Genotype
i. The alleles that make up a persons genome
e. Mutation
i. An allele that is different from the wildtype
f. Permutation
i. A permutation is a mutation that is not in affect in the carrier but
when passed on to the offspring it has the possibility of becoming
a mutation. Such as Fragile X syndrome in a trinucleotide
expansion
g. Wild type
i. The most common naturally occurring allele in the gene pool
2. Distinguish why it is more difficult to determine inheritance patterns in humans
than in experimental animals such as fruit flies. Describe how such patterns are
ascertained in humans.
a. In humans, specific mating patterns cannot be established as they can be
in fruit flies. They try to link up the inheritance patterened based off of
the offspring and my involving multiple families that have the same trait.
3. Calculate genetic risk by using a Punnett square.
a. 4x4 square for 2 traits, 2x2 square for 1 trait.
4. Define pleiotrophy.
a. A gene that has more than one effect on the phenotype, or has multiply
effects on the anatomy or physiology of the person. Marfan’s syndrome,
CF, etc.
5. Compare/contrast variable expressivity and penetrance and their clinical
presentations.
a. In variable expressivity there is always expression of the trait, ranging
from severe to mild, however in penetrance the person can have the trait
and not express it or they can have the trait and express it, there is not
differing forms of severity. Clinically, if it is variable expressivity then the
person may have a mild form of Marfans syndrome, but in penetrance
either a person has a disorder or a person doesn’t.
6. Explain why most lethal autosomal dominant traits are inherited from a mosaic
parent or result from de novo mutations.
a. Lethal dominant traits require mosaics so the person is only half effected
from the trait. They have 2 separate germ lines that are supplying their
genetic needs, there for they can carrier the lethal mutation with out it
killing them and they can pass it on. De novo mutations that are lethal
occur after conception and allow for the trait to be created within the
person.
7. What kinds of lethal dominant traits can be directly passed through several
generations?
a. Huntingdon’s because it is late onset so the person can mate and pass it
on before the gene kills them
8. Define and give an example of codominance.
a. Co-dominance
v. The full expression of both alleles at the loci.
vi. Blood type is the classic example of this, both express AB if they
carry the A and B allele.
9. Define consanguinity and explain why it increases the probability of having a
child with a genetic disorder.
a. Consanguity is the inheritance of an allele from a common ancestor. If
two people breed that come from a common ancestor, the likely hood of
them carrying a mutated gene at the same loci is much higher than 2 nonrelated people.
10. Define locus heterogeneity and distinguish its effect on genetic inheritance.
a. Different locus when mutated can cause the same phenotype, so when a
trait is passed on its phenotype is determined by more than 1 locus.
11. Explain why males are more commonly affected by a recessive trait carried on
the X chromosome.
a. Females require 2 X’s men only have 1 the odds of a female having 2
recessive alleles is much lower than a man receiving just one recessive
allele, there men are more affected by recessive traits on the X
chromosome.
12. Define the tenants of the Lyon hypothesis and recognize the results of these
tenants in females. Define skewed inactivation.
a. The tenants of the Lyon’s hypothesis are that one X of the female genome
is inactivated so as not to have twice the amount of X chromosomes than
males. The inactivation of an X is a random event, but it is not random for
a cell, and it can result in a phenotypic change in the cell line that
surrounds it, such as fur coat color in cats.
13. Distinguish why it is difficult to determine an X-linked dominant trait from a
pedigree.
a. If the trait starts with the female then all of the progeny will have the trait
in F1, so it takes the second generation to determine if the trait is
autosomal dominant or X linked dominant. And if a man with the trait
from F1 doesn’t have a son then you will not be able to identify it.
14. Recognize the pedigree for a Y-linked trait. Name the two traits inherited via this
mode.
a. 2 traits that are inherited via the Y chromosome are the H-Y
histocompatability antigen and the genes for spermatogenesis.
15. Distinguish the clinical presentation of traits inherited via partial sex linkage.
a. Partial sex linkage is from the pseudoautosomal inheritance on sex
chromosomes. Because of the homology between the X and the Y certain
traits can cross over affecting at randonm a male then a female. It mimics
autosomal inheritance when crossing over but it is usually a father to son
transmission. Example: dyschondrosteosis
16. Distinguish between the pedigrees for the following modes of inheritance:
autosomal dominant, autosomal recessive, X-linked recessive, X-linked dominant
and Y-linked recessive.
a. Please note that the pedigrees shown are merely examples which have
been pulled from the internet. Make sure you understand how to
interpret inheritance from a pedigree.
b. Autosomal Dominant
c. Autosomal Recessive
d. X-linked Recessive
e. X-linked Dominant
f. Y-Linked Recessive
17. Define multiple alleles and give an example. Calculate genetic risk using a
Punnett square.
a. Having multiple options for one locus, and be able to form a punnet
square from a scenario and tell the potential outcomes.
18. Distinguish between the following non-Mendelian patterns of inheritance:
a. Anticipation
i. In anticipation inheritance the trait is transmitted and shows its
phenotype in a younger age each time it is passed on. Huntingdons
is one disease where this occurs, due to the CAG repeats. The more
repeats the earlier the onset, and it is parental biased so that when
it is passed from the father there is an earlier onset then when
passed from the mother.
b. Mosaicism (somatic and gonadic)
i. Somatic mosaicism is where there was a mutation in the cell line
present in the body during expansion, so not all the cell has this
mutation and it resticted to that cell’s progeny, so it is restricted to
areas of the body. If it is a gametic region of the body where this is
a mutation then the person will be normal but the offspring will
show the disorder without a mosaic effect because the cell line
started with the mutation. Dominant disease in a child from
unaffected parents it points to a germ cell mosaic
c. Uniparental disomy
i. In normal inheritance the offspring receive only one of the pair of
homologous chromosomes from one of the parents, but if a nondisjunction occurs and it fuses with an egg or sperm then there
will be a trimosy effect, then if the chromosome is losed a normal
cell is formed and can then make a normal cell with the right
amount of chromosomes. A heterosomy is formed at a meiosis 1
nondisjunction and an isodisomy is formed at a meiosis 2
nondisjunction.
19. Distinguish between polygenic and multifactorial inheritance.
a. Polygenic inheritance
i. Person obtains multiple genes from parents and these have a
synergistic effect and interact with each other. Non-mendelian
ratios, they produce a bell curve of phenotypes or Gaussian curve
within the population, such as height. The environment can affect
them but the genes play more of a dominant role in those traits,
such as IQ, height, skin color, blood pressure. The more loci
involved the greater the spread of the bell curve. The more loci
involved in the inheritance the more spread out the curve is an the
more it solidifies the theory that it is a polygenic effect. How ever,
there can be an environmental impact on polygenic traits even
though it is slight, and some genes in the group may have more of
dominant effect on the trait than other, but a bell curve still exists.
b. Multifactorial
i. There is a more interactive affect of environment with the genes
than the genes making a dominant role in expression.
20. Compare/contrast the presentations of monogenic and polygenic traits present
within a population. Given a specific trait, choose its mode of inheritance.
a. Monogenic traits are pasted via classical Mendelian ratios and have a onegene-one-effect ratio. In polygenetic rate there is a cummalative effect in
the amount of loci for genes to the dominance of the phenotype.
21. Determine if a trait is polygenic or multifactorial.
a. Polygenic will form the bell curve and forms a ratio even though it is nonMendelian ratio. It allows for measurement of quantivative values such as
height, blood pressure and IQ.
b. Multifactorial- it measures a liability whether it is genetic or
environmental on a populace. It forms a variable curve in the general
populace as well as in a family. The curve is formed allowing
measurement of incidence as well as forming a incidence border on the
right, and once an individual passes the incidence border he presents
with the disease (all or nothing).