Exam 2

Question 1

Stem Cell Overview

Answer 1

Stem cells divide by mitosis, has self-renewal, can differentiate into other more specialized cells, this is called a progenitor cell (between stem and specialized cells)

Produces daughter cells that retain the ability to divide and some that specialize

Progenitor cells do not have the capacity of self-renewal

A fertilized egg becomes a stem cell that self-renews, and the stem cells become progenitor cells that become more specialized

Question 2

Potency

Answer 2

Stem cells and progenitor cells are described in terms of their development potential

Totipotent - the least specialized stem cell, the fertilized egg, can become all different cell types
Pluripotent - a little more specialized, has started the process of specialization, but can still become different cell types
Multipotent - even more specialized, can become 3 of 4 different cell types at this point
Unipotent - the most specialized, is only one type of cell

Genes control stem cell development and potency
In a totipotent cell all genes (entire genome) can be expressed
Pluripotent most genes can be expressed, but some can no longer
Multipotent cells can only express some of the genes
Unipotent cells express even less genes

Question 3

Sources of Stem Cells

Answer 3

1. Embryonic stem cells - created in a lab dish using the inner cell mass (ICM) of an embryo, come from discarded embryos
2. Induced pluripotent stem (iPS) cells - somatic cells reprogrammed to differentiate into any of several cell types, created in lab
3. Adult stem cells - Tissue-specific or somatic stem cells, we still have some specific multipotent stem cells in case we get injured. Adult stem cells are more differentiated than embryonic stem cells
4. Umbilical Cord stem cells - come from the umbilical cord of the baby because it has a high percentage of stem cells

Question 4

Uses of Stem Cells

Answer 4

1. Discovery and Development of drugs
2. Observing the earliest sign of disease
   (Sometimes things like cancers and type 2 diabetes are not known until after they have already developed, so stem cells are used to study the beginning of these disease)
3. Treatment of disease via implants and transplants
4. Stimulating stem cells in the body via the introduction of reprogramming proteins

Stem cells were used in the development of the COVID vaccines

Question 5

Banking Stem Cells

Answer 5

Concept: Companies store stem cells (most commonly cord blood) for a fee in case patients need the cells for future treatment
Fees: Initial fee + Annual Fee
Regulation: None
Diseases treatable with cells: 70+ (example: lysosomal storage disorders)
Stem cell transplant is an accepted form of treatment and has been performed numerous times

Some things to consider:
Treatable diseases are rare
Often they cannot be treated by someone else’s stem cells
Banks are not regulated and some cells are not usable when needed
Most cells are never used and discarded

Stem cells are also maintained in regulated banks:
Operated at NIH and many Universities (none at Springfield)
Cells are donated
Almost all cells are used
Conditions are regulated by the government
No cost to the individual

Question 6

Savior Siblings

Answer 6

The idea of having a child to save your current child

Ex. Molly was born with Fanconi Anemia. Lisa and Jack were told an umbilical cord transplant stem cell transplant from a sibling would save Molly. With a 1 in 4 chance of the new baby having the same disorder, the Nash family did not want another child. Decided to have Adam, and a month after his birth, his umbilical stem cells were infused into Molly

Question 7

Fertility Definitions

Answer 7

Infertility - people cannot conceive on their own, does not conceive after 12 months of trying
Normal fertility - 3 to 4 months is how longer it typically takes to conceive a baby
Subfertility - Anywhere between 4 to 12 months of trying to conceive

1 in 6 couples undergo infertility issues
90% of the time we can identify the cause of infertility
30% male, 60% female infertility

Question 8

Male Infertility

Answer 8

Low sperm count (oligospermia) - Affects 1 in 25 men, most common infertility in males

A malfunctioning immune system

A varicose vein in the scrotum

Structural sperm defects

(Most of these are genetic)

Question 9

Female Infertility

Answer 9

Many women with subfertility or infertility have irregular menstrual cycles, most common out of all infertility, the longer the egg is arrested, the greater the chance of abnormality occurring

Abnormalities in any part of the female reproductive system can cause infertility

Blocked fallopian tubes can result in ectopic pregnancy (tubal pregnancy), Ectopic pregnancy is any pregnancy that is not in the uterus, and it is very dangerous

Excess tissue growth in uterine lining may make it inhospitable for an embryo, Fibroids: benign tumors, Endometriosis: buildup of uterine lining

Secretion in the vagina and cervix may be hostile to sperm

Infertility may also result if the oocyte fails to release sperm-attracting chemicals

Early Pregnancy loss due to an abnormal chromosome number is more common in older females, May appear as infertility because bleeding resembles a heavy menstrual flow

PCOS is Polycystic Ovarian Syndrome, Cysts exist in the ovaries, making it hard to ovulate (menstruate), Affects anywhere from 1 in 25 to 1 in 5 females

Question 10

Intrauterine Insemination

Answer 10

Putting sperm directly into the uterus
Female is the genetic and gestational parent
Male can be the genetic or gestational parent, but it could also be donor, If a person wants a kid w/o a husband they use donor, If the father has a genetic disorder or low sperm count
Most commonly used to treat oligospermia
Fertilization occurs inside of the female
Success Rate is only around 20%
A possible issue is that ethical issues arise: Should we sort between X and Y chromosomes? Can create weird situations if a sperm donor is used.

Question 11

Surrogate Motherhood

Answer 11

There is an issue that prevents a women from carrying a child, so a surrogate mother holds the baby
The surrogate is the gestational, but it can also be the genetic
The father is the gestational and genetic
Fertilization occurs in the surrogate
Issues? The birth certificate shows the surrogate as the mom, so the surrogate can take legal ownership over the child (even if the child’s egg is not from the surrogate)

Question 12

In Vitro Fertilization

Answer 12

The zygote is formed outside of the body, in a lab
The egg and sperms are harvested, and put into a culture dish
Fertilization happens in the lab
The zygote or embryo are then transferred into the female reproductive tract, You still usually put it in the fallopian tubes
The mother is the genetic and gestational parent
The father is the genetic and gestational parent
Can be used for blockage of fallopian tubes, irregular menstrual cycles, and a lot of other causes of infertility
Only has a 25% success rate

Complications
Most physicians transfer 3 to 5 embryos in case some don’t transfer, This could cause issues during pregnancy if multiple embryos implant into the uterus
Usually there are extra embryos made in the lab that aren’t put into the body, These can be thrown away or frozen
There is also an increase of birth weight and an increase of birth defects

Question 13

Intracytoplasmic Sperm Injection

Answer 13

The sperm is injected into an egg
Fertilization happens in the lab
This is a way to improve the success rate of IVF by about 5-10%

Question 14

Gamete Intrafallopian Transfer

Answer 14

Transferring a sperm and an egg independently into the fallopian tube
Fertilization occurs in the female body
This treats fallopian blockage
Less costly than IVF but only has a 20% success rate

Question 15

Zygote Intrafallopian Transfer

Answer 15

Transferring a zygote directly into the fallopian tube
Fertilization occurs in the lab
Has about a 25% success rate
Also treats fallopian blockage but is is also used after IVF to increase the chance of pregnancy

Question 16

Oocyte Banking & Donation

Answer 16

We can do this for a variety of reasons - Cancer, aging, etc.
Only about 5% success rate
The problem is the chromosomes are still in metaphase or prophase and it’s hard for the chromosomes to be in the right place after the egg is unfrozen.
Taking a strip of the ovary instead of an egg itself has increased the success rate by about 25%

Question 17

Preimplantation Genetic Diagnosis

Answer 17

This is an add on to IVF
When 8 cells are developed, the scientist takes 1 and this doesn’t interfere with the development of the baby
They then test the one cell and can determine some of the diseases
The issue is that mosaicism exists (the cells have slight variations)
This leads to about a 3% failure rate

cnt.
Can determine if an embryo has certain genetic disorders (like how many chromosomes, if it has CF)
Only capable of this if it is in vitro fertilization
Out of 8 cells one gets tested, and this does not affect it’s development (at least not that we’ve seen so far)
This does have it’s fallacies, not all cells have the exact same genetic material as the others. It is around 97% accurate in determining the function of the organism.
It is good at determining things, but since in vitro fertilization has a low success rate, it has a low success rate in actually forming a baby
BRC1 and BRC2 are the genes responsible for ovarian and breast cancer

Question 18

Fates of Frozen Embryos

Answer 18

1. Store indefinitely
2. Store and destroy after a set time
3. Donate for embryonic stem cell derivation and research
4. Thaw later for use by biological parents
5. Thaw later for use by other parents
6. Discard

Question 19

Lethal Alleles & Achondroplasia

Answer 19

Causes death before the individual can reproduce
This stops the transmission of certain genes and prevents them from showing up on a pedigree
Lethal alleles are most common in autosomal dominant traits
Specifically when you possess 2 dominant alleles

Achondroplasia is an example
Autosomal dominant
Short stature in the 2% of that growth curve, facial dismorphology, they have poor muscle tone, regular IQ and life expectancy
98% of patients have the same 1 base-pair mutation in the FGFR2 (Fibroblast Growth Factor Receptor)
Expectations: 1/4 unaffected, 3/4 affected
Reality: 1/3 unaffected, 2/3 affected
80% of them do not inherent them from a parent, it is usually just a mutation

Mexican hairless dog is also an example

Question 20

Multiple Alleles

Answer 20

An individual carries two alles for each autosomal gene
However, a gene can have multiple alleles because its sequence can deviate in many ways
Multiple Alleles is autosomal recessive condition usually

Compound Heterozygote: Has the autosomal recessive condition because two different disease causing alleles

CFTR is an example of this because it has around 1700 different possible mutations
23 of these mutations make up the most common mutations
75% of individuals with this disease are compound heterozygote
This also has variable expressivity

Question 21

Single Gene Inheritance & Factors that Affect Phenotype

Answer 21

Single Gene Inheritance: Give nice genotyping and phenotypic ratios, rarely completely control the phenotype

Factors: Environmental Stimuli, other protein encoding genes, other DNA sequences, RNA sequences

Question 22

Mendel’s First Law: Segregation

Answer 22

Equal allele distribution
Random combination of gametes

Dominant or recessive is important in determining the reoccurrence risk

Reflect the characteristics or abundance of a protein:
Recessive traits have: a loss of something, stay hidden in a population, affect younger individuals, and impact ability to reproduce
Dominant traits have: a gain of function, stay or remain in a population, typically affect adults, and don’t impact ability to reproduce

Recessive disorders tend to be more severe (book)

Question 23

Mendel’s Second Law: Independent Assortment

Answer 23

Considers 2 genes on different chromosomes

The inheritance of one does not influence the chance of inheritance the other

Independent assortment results from the random alignment of chromosome pairs during metaphase 1 of meiosis

Question 24

CRISPR/Cas9

Answer 24

This is a gene editing tool derived from bacteria (CRISPR)

It is a series of enzymes that remove a gene and replace it (CAS9)

This is important for changing genetic disease, but it isn’t clear cut
They have off target effects because one gene can affect multiple things

CRISPR has been used in human embryos before, but there is still debate as to what is ethical
Right now we are not allowed to implant embryos modified by CRISPR
The one person who did this is now in prison

Question 25

Polar Body Biopsy

Answer 25

The polar bodies can be retrieved from the oocyte
The genes in the polar body are the opposite of what’s inside of the egg, so it gives us a lot of information

Question 26

Lethal Alleles:

Answer 26

Causes death before the individual can reproduce
This stops the transmission of certain genes and prevents them from showing up on a pedigree
Lethal alleles are most common in autosomal dominant traits
Specifically when you possess 2 dominant alleles

Achondroplasia is an example
Autosomal dominant
Short stature in the 2% of that growth curve, facial dismorphology, they have poor muscle tone, regular IQ and life expectancy
98% of patients have the same 1 base-pair mutation in the FGFR2 (Fibroblast Growth Factor Receptor)
Expectations: 1/4 unaffected, 3/4 affected
Reality: 1/3 unaffected, 2/3 affected
80% of them do not inherent them from a parent, it is usually just a mutation

Mexican hairless dog is also an example

Question 27

Multiple Alleles

Answer 27

An individual carries two alleles for each autosomal gene, however a gene can have multiple alleles because its sequence can deviate in many ways

This is autosomal recessive

Compound Heterozygote:
Has the autosomal recessive condition because two different disease causing alleles
CFTR is an example of this because it has around 1700 different possible mutations
23 of these mutations make up the most common mutations
75% of individuals with this disease are compound heterozygote

This also has variable expressivity

Question 28

Incomplete Dominance

Answer 28

Somewhere in between dominant and recessive

Familial Hypercholesterolemia
High cholesterol in blood
Genetic disorder in which the LDL receptor is not functioning correctly
This is an incomplete dominance disorder
The general population’s blood cholesterol level is lower than that of a heterozygote for the condition and that is lower than that of a homozygous dominant individual.

We typically see heart attacks in the population around 50 to 60 years of age, but individuals start having heart attacks when they’re younger than that

Question 29

Codominance

Answer 29

The heterozygote phenotype results from the expression of both alleles

Blood Type:
A, B, AB, and O blood types
The capital “i” gene determines what blood type you are
I^A I^B and i are the possible alleles
The linker protein (coded for by another gene) attaches the A or B antigen to the cell (the linker protein still exists in O)

Question 30

Epistasis

Answer 30

The phenomenon where one gene affects the expression of a second gene

Bombay Phenotype:
The H gene is epsistatic for the “I” gene
The H gene codes for the linker protein
H protein places a molecule at the cell surface to which the A or B antigens are attached
hh genotype: no linker protein (causes O blood type)

Question 31

Pleiotropy

Answer 31

Molecular definition; when a single protein affects different body parts (one gene affects multiple traits)

Porphyria:
A missing enzyme causes porphyry in to accumulate
This results in a wide range of symptoms

Marfan Syndrome:
People with Marfan syndrome are tall (above the 98th percentile), long arms, and long legs, they also have pectis ectovoban (chest cavity), and connective tissue (ligaments and tendon) issues which is called joint laxity,
also cardiac issues like cardiac arrest because the aorta enlarges
Also ocular issues because of the connective tissue (the lens dislocates)
Autosomal Dominant Condition (Fibrilin protein which deals with connective tissues, gene FBM1)

Question 32

Genetic Heterogeneity

Answer 32

Different genes can produce identical phenotypes
Hearing loss can result from 132 autosomal recessive forms

Ex. Question: John has hearing loss due to a mutations in Gene A (aa), Sarah has hearing loss due to mutations in Gene B (bb), what is the percent chance their offspring has hearing loss?
Answer: Inconclusive, genetic heterogeneity

Osteogenesis imperfects (brittle bones) - at least two different genes involved
Alzheimer’s disease - at least four different genes involved
Leber Congenital Amaurosis - 3 genes affecting cones, 4 genes affecting rods, any mutation can cause blindness

Question 33

Mitochondrial Traits

Answer 33

only pass down from the mother to all the children
The genes in the mitochondria are circular, and there is much less (only 37 genes, hundreds of thousands of copy of the genome in the mitochondria whereas the nucleus only has two copies)
This is because the product of ATP are free radicals so we need multiple copies
Most of the genes are involved in making ATP

Question 34

Differences of Mitochondrial Genome

Answer 34

No crossing over
Few types of DNA repair
Only mother gives
Many copies per mitochondria and per cell
High exposure to oxygen free radicals
No histones
Genes not interrupted
Circular genes

Question 35

Phenocopy

Answer 35

A trait that appears inherited but is caused by the environment
May have symptoms that resemble an inherited trait or occur within families
Ex. HIV, Phocomelia (abnormality of upper extremities caused by thalidomide)

Question 36

Linkage

Answer 36

Genes on the same chromosome are said to be linked
Linked genes do not assort independently in meiosis
Rather, they are usually inherited together when the chromosome is packaged into a gamete
Therefore, they do not produce typical Mendelian ratios