Midterm 4 Flashcards
1
Q
what is limited and has competition
A
RESOURCES–> resources are limited; there is competition for those resources
2
Q
what changes over time?
A
the distribution of alleles and genotype changes over time
3
Q
Population genetics aim to …
A
make quantitative predictions and provide mathematical insights into the dynamics of allele frequencies and genotype frequencies in populations
4
Q
what is a population
A
group of organisms of the same species living in the same geographical area
5
Q
what is a gene pool
A
all alleles in population
6
Q
genotype frequency
A
proportion of individuals in a population with a specific genotype
7
Q
allele frequency
A
proportion of alleles in a population
8
Q
genotype frequency does NOT equal
A
allele frequency
9
Q
when does allele frequency equal genotype frequencies?
A
Bacteria
There is no homozygous or heterozygous
One allele for each gene
X-linked gene
Homozygous
10
Q
one gene has how many alleles
A
one gene haas 2 alleles
11
Q
p and q are what ??
A
shorthand notation for allele frequencies
12
Q
what is the Hardy-Weinberg Equation?
A
p^2+2pq+ q^2= (p+q)^2=1
13
Q
from generation to generation what doesnt change
A
allele frequencies and genotype frequencies
14
Q
what are the hardy Weinberg conditions
A
- migration in/out is absent (no gene flow)
- Large population (no genetic drift)
- No mutations
- Equivalent viability and fertility (no selection)
- Mating is random
- Same allelic frequencies in men and women
15
Q
hardy weinberg conditions are rarely…
A
rarely met but helps us learn why allele frequencies change –> often met “close enough” mating is random for most genes
16
Q
what is p^2
A
AA genotype frequency
17
Q
what is 2pq
A
Aa genotype frequency
18
Q
what is q^2
A
aa genotype frequency
19
Q
what does the p and q in this relate too –> (p+q)^2
A
p is the A frequency
q is the a frequency
20
Q
what will all genotype and allele frequencies add up too
A
always add up to 1 whether or not the population is in HW
21
Q
if we know genotype frequencies in a population, when can we calculate corresponding allele frequencies?
a) if population is in HWE
b) if we know allele frequency of one of the allele
c) if population is not in HW equilibrium
D) any of the above
A
D) any of the above
22
Q
if we know GF’s in a population, then we can always ….
A
calculate AF’s whether or not the population is in HW equilibrium
23
Q
if we know Af;s we can only calculate…
A
GF’s if the population is in HW equilibrium and autosomal locus has two alleles
24
Q
If we have X-linked recessive a allele, genotype frequencies among males are the same as allele frequencies:
A
Frequency of XAY males = p
Frequency of XaY males = q
25
forces that can cause deviation from HW ratios
1. gene flow (migration)
2. genetic drift (small population)
3. Muations
4. Selection
5. Inbreeding
6. Different allelic frequencies in males and females
26
Which of these forces does not
contribute to Evolution?
1. Gene flow
2. Genetic drift
3. Mutations
4. Selection
5. Inbreeding
6. All contribute
6- all contribute
27
evolution=
long lasting changes in the gene pool due to natural selection and other forces ( mutation, drift)
28
Gene flow example
migration example is gene flow between human subspecies --> Neandetals which caused 2% of DNA in europeans and east asians from Neandertals alleles that are potentially adaptive
29
genetic drift?
random events that can result in very good dominant allele being eliminated from the population
30
the vast majority of good alleles/genes that arose during our evolution ...
did not end up in our gene pool
31
two types of genetic drift
bottleneck effect and founders effect
32
example of bottle neck effect
northern elephant seal population
Hunted to near extinction
* Population decreased to 20 individuals in 1800’s.
* Those 20 repopulated so today’s population is
~30,000
* Very low level of genetic variation
33
founders effect
when smalll group from population migrate to form new population
34
example of founders effect in human population
--> Old Order Amish populations are derived from a few dozen colonists who escaped religious persecution in Germany in 1719 to
settle in Pennsylvania.
* The community is closed.
* Allele and genetic disease frequencies in Amish are significantly different from the German ancestral and the surrounding local populations.
35
a random mutation is ...
far more likely to harm the function of a protein than to enhance it
36
if mutations was the only force operating on the gene pool, then eventually
most alleles would become nonfunctional
37
how many bad (lethal) recessive mutations an average person carries?
1-2
38
Humans carry on average one to two mutations that, if inherited from both parents, can cause...
severe genetic disorders or death before reaching
reproductive age
39
Natural selection
more organisms are produces each generation than can survive and reproduce
Organisms differ in their ability to compete, based
(in part) on their genotype
*Hence, genotypes that promote
survival/reproduction are favored, and are more likely to contribute alleles to the next generation’s gene pool
40
forces that keep bad alleles in gene pools despite natural selection
1. delayed age of disease onset
2. slow selection against recessive alleles
3. mutation selection equilibrium
4. heterozygote superiority
41
in haploid organisms selection is ____-
efficiennt
42
why are haploid organism's selection efficient
No recessive/dominant alleles means that a very weak selective advantage can quickly lead to a favored allele becoming fixed
43
In diploids, selection for/against
recessive alleles is
inefficient
44
why are diploids, selection for/against
recessive alleles is inefficient
Rare disease-causing recessive alleles
persist in the population in heterozygote carriers, even if they are lethal when homozygous
45
disease incident?
q^2
46
fraction of disease alleles in patients?
q
47
fraction of disease alleles in carries?
p
48
the rarer the recessive disease....
the greater the % of alleles that are in carries
49
alleles in carries are ...
hidden from selection
50
function of selection and new mutations
selection = eliminates harmful alleles
new mutation = generate harmful new alleles
51
describe the relationship between selection and new mutations
These forces push the population out of HW equilibrium, but they push in OPPOSITE directions
Over time, an equilibrium is reached where allele frequencies are stable - new alleles are removed by selection at the same rate they are created by
mutation
52
bad alleles are a ...
stable part of the gene pool
53
Malaria
A serious, infectious disease
(~300 million annual cases; ~1 million deaths)
* Flu-like symptoms, anemia, jaundice
->kidney failure, coma, death
* Caused by infection with the parasite Plasmodium
* Transmitted by mosquito bites
* Kills Red Blood Cells and releases toxins into bloodstream
54
Sickle Cell Anemia
-Autosomal recessive, incidence 1/500 among AA
* Gain-of-function mutation in the gene encoding the b chain of
hemoglobin → causes Hb aggregation which in turn
deforms red blood cells (RBCs)
* Sporadic vessel clotting causes acute pain, organ failure
* Shorter half-life of RBCs causes anemia
55
Heterozygote Superiority
(or advantage)
Homozygous normal (SS)
* Reduced survival because of Malaria
Homozygous recessive (ss)
* Reduced survival because of Sickle cell anemia
Heterozygous carrier (Ss)
* Survival and reproductive advantage
56
result of slow selection against recessive alleles
most disease causing recessive alleles are in carriers, not patients
57
result of mutation-selection equilibrium
Result: disease-causing alleles are a stable part of our gene pool --> we’re all genetically defective
58
result of heterozygote superiority
Result: “bad” alleles may be good in some contexts
59
inbreeding affect on individual
Increases the risk of having a
kid homozygous for a rare recessive allele
60
inbreeding affect on population
Results in an excess of
homozygotes compared with random
mating
61
how to check for HWE
If a population is in HW equil., then genotype and allele freqs. should be related as follows:
AFs should correctly predict GFs
Freq (AA) = p2
Freq (aa) = q2
Freq (Aa) = 2pq
62
complex or quantitative trait is a
measurable phenotype that depends on the cumulative actions of many genes and the environmnent
63
multiple additive genes can give rise to ...
continuous variation
64
With lots of additive genes it starts to look like a...
normal distribution
65
what are the properties of quantitative traits
1. polygenic
2. multifactoral
66
polygenic?
variation is caused by the combined effects of multiple genes
67
multifactorial?
variation is caused by the combined effects of genes and environments
68
When considering an additive trait, the
larger the number of genes controlling
the trait, the _____ the number of
phenotypes
A. Larger
B. Smaller
C. Same
A) larger
69
examples of quantitative/complex traits
height
weight
blood pressure
eye color
personality
heart disease
diabetes
alzheimers disease
70
quantitative traits fit what??
normal distribution
71
threshold trait examples?
autism, most birth defects
heart disease, diabetes, alzeihmer's disease,
72
threshold traits are .....!
multifactorial (environment matters
73
Threshold traits description
traits that are all or none, but appear to be influenced by multiple genes and the environment.--> think diabetes bc you have diabetes only if your blood in your sugar reaches a certain threshold
74
phenotypic variance is a...
sum of environmental variance (Ve) and genetic variance (Vg)
75
Environmental variance?
Ve= the portion
of phenotypic variance that is due to
differences in the environments to which the individuals have been exposed.
76
broad sense heritabilty?
H^2 is between 0 and 1 and is proportion of the total variance of a trait that is caused by genetic variation
77
equation for H^2
H^2= Vg/ (Vg +Ve)
78
H^2 is also known as
broad sense heritability
79
how to asses environmental variance in human population
Comparisons of variability between
identical twins can be used to estimate
heritability
80
identical twins arise from
the splitting of a single fertilized egg --. clones --> all alleles identical
81
If there is variation in a trait between two identical twins,
then that variation must have been caused by environmental,
not genetic factors
82
example of variation due to environment in identical twins
Fingerprints differ between
identical twins -> Variation in
fingerprints is due to environment
83
Little variation in a trait (e.g height) between identical twins - the cause is genetic?
Not necessarily, because identical twins
are usually raised in a very similar
environment
84
Little variation in a trait (e.g height) between identical twins - Solutions?
Solution 1: Compare to fraternal twins.
If variation in a trait between fraternal
twins is greater than variation between
identical twins
--> that additional variation is presumed to
be due to genetic differences
Solution 2: Use reared apart identical
twins and compare to random people
85
Fraternal twins have ________ _________,
while most identical twins share______
Fraternal twins have separate placentas, while most identical twins share placenta
86
Which of the following is TRUE about
twin studies?
A. Differences between identical twins can be
due to genes or the environment
B. Differences between fraternal twins are due
to the environment only
C. If there is a genetic component to a trait, you
would expect more variation between
identical than fraternal twins
D. If a trait has a heritability near 0, identical
twins reared apart from each other will
vary as much as two random people
D. If a trait has a heritability near 0, identical
twins reared apart from each other will
vary as much as two random people
87
*H2 near 1.0 -->
identical twins will have the
same value for the trait, even if they are reared apart*
88
H2 near 0 -->
identical twins reared apart
from each other are no more likely to have the same value for the trait than any two random people
89
Vaccines do not cause....!
autism
90
why are the genetics of autism complex?
identical twins reared apart
from each other are no more likely to have the same value for the trait than any two random people
PROBABLY both since many gene sare implicated in autism (some epistatic) but environment also plays a role
91
concordance?
is the likelihood that a pair of individuals will share a trait or characteristic if one of them does.
92
autism and concordance?
A 1977 study found 82% concordance in identical twins vs. 10% in fraternal twins.
93
Do organismal clones ever occur naturally?
bacteria
twins
plants
mitosis
94
explain the cloning the vertebrate from somatic cells
too cell and put UV radiation on it, then they inserted an intestinal cell of a baby frog and it became a cloned frog
95
cloning the first mammal pathway
take egg donor (black sheep) and remove nucleous from the egg, then add the mamary cells from white sheep and combine. The blastocyst is then placed in uterus of a surrogate EWe and DOLLY IS BORN
96
what is the result of cloning the first mammal
result is a genitally identical copy sheep
97
what is the only other way (other than cloning ) where mammals have the same exact genotype
identical twins
98
epigenetics?
is the study of heritable phenotype changes that do not involve alteration in the DNA sequence
99
why did the clone of the cat Rainbow result in a copy cat with diffent fur color
Even though two cats are genetically identical,
epigenetic process called X-inactivation causes
random orange making gene gene inactivation
during development
100
What causes rainbow fur color in calico Cats
x-inactivation
101
can make cats have rainbow color?
no, and yes in very rare instance
102
when was the first primate cloned
2018
103
Ethical issues with reproducing cloning of humans
Dozens of cloned embryos must be created and
placed into surrogate mothers to produce a single
live birth
* Dying, stillborn and deformed babies frequent
* Even those who have lived a long time (such as
Dolly) have a some of serious health problems
* It would diminish the sense of the uniqueness of an
individual
104
has reproductive cloning of human happened yet?
no
105
what is reproductive cloning
cloning to make a baby
106
Embryonic Stem Cells
(ES Cells) hold ....
a great
potential for treating
disease
107
ES cells have the theoretical. potential to ...
differentiate into any
cell in the body (->
they are pluripotent)
108
Some merits of therapeutic cloning
- Rebuild the pancreas of
someone with type-I diabetes
* Replace dead neurons in
patients with spinal cord
injuries
* Replace failed heart muscle
etc.
- If patients are treated with
stem cells derived from their
own tissue, immune rejection
will be less likely
109
ethical issues with therapeutic cloning of humans
- Therapeutic cloning, while offering the potential for
treating humans suffering from disease or injury,
would require the destruction of very early human
embryos in the test tube.
* Opponents argue that using this technique to
collect embryonic stem cells is wrong, regardless
of whether such cells are used to benefit sick or
injured people
110
DNA cloning synonym
molecular cloning
111
DNA cloning is...
is a molecular biology technique
that makes many identical copies of a piece of
DNA, such as a gene
112
DNA cloning greatly aids...
further study of that gene,
and its use in diagnosis or treatment
113
DNA cloning steps
1. A target gene is inserted into a circular piece of DNA
called a plasmid (Ligation).
2. The plasmid is introduced into bacteria via a
transformation, and bacteria carrying the plasmid
are selected using antibiotics.
3. Bacteria with the correct plasmid are used to make
more plasmid DNA
114
restriction site?
A short DNA sequence
that can be cleaved by a restriction enzyme
115
vector
a carrier for recombinant DNA
116
characteristics of vectors
- Typically small (<10 Kbp) extrachromosomal
element such as a plasmid or a phage
* Has restriction enzyme site and selection
marker (antibiotic resistance gene)
117
DNA ligase catalyzes
phosphodiester
bond formation between a free 3’ OH
and a free 5’ PO
118
Since the same sticky ends are on ‘both
sides’ of the vector and insert,
the insert
can ligate into the vector in either of two
orientations
119
How many different ligation
products besides desired will be isolated after transformation?
greater than 3
120
example application of DNA cloning
insulin production for diabetic patients + mRNA vaccines against COVID 19 you need to first clone the viral gene
121
4 applications of gene cloning -general
- Biopharmaceuticals (Insulin, human growth
hormones, mRNA vaccines etc.)
* Gene analysis for basic research (to study gene
function, need to clone it first)
* Gene therapy (fixed copy of a gene)
* Every molecular biology lab uses DNA cloning
122
How to understand the genetic basis of the trait or disease
step 1- map the genes responsible fro trait/disease
step 2 - clone the canidate gene
step 3- understand the function of the gene using model organisms (create a gene knowck out or a transgene)
step 4- designa drug or use gene editing to cure a genetic disease
123
positional cloning :
map the gene first then clone
124
HOw to map human genes
Linkage Analysis
Genome Wide Association Studies
Whole Genome or Exome Sequencing
125
Linkage analysis is based on
co-inheritance
of disease genes and neighboring regions
126
A genetic marker is a
DNA sequence with a known
physical location on a chromosome, a “landmark”
127
DNA segments close to each other on a
chromosome tend to be
inherited together (linkage)
128
Genetic marker that is close to the gene will be...
`inherited together with the gene because of linkage
129
Genetic markers ______ between individuals to the extend that ...
Genetic markers VARY between individuals to the
extent that they can be used to find a nearby gene
causing a certain disease or trait within a family.
130
LOD score is a
statistical estimate
whether a disease
gene and a marker,
are likely to be
located near each
other on a
chromosome.
131
LOD score >3 means that
marker and gene are likely
linked, and gene is mapped
132
GWAS (Genome-Wide Association Studies) are also
based on
co-inheritance of disease genes and
neighboring genetic markers (or polymorphisms) but
has much higher resolution
133
GWAS is especially powerful for identifying
genes responsible for complex traits
134
WGS or WES (Whole-Genome or WholeExome Sequencing) of patients is increasingly used to identify
gene mutations responsible for rare diseases
135
what is the caveat of WGS or WES
very expensive, price of DNA sequencing goes down every tear
136
How to clone a human genes
look at human genome take gene of interest and isolate from genome then insert that gene into plasmis and then that plasmid is inserted into bacterial population generating clones of this gene
137
why is it easy to clone a human gene now
because
we know entire human
genome sequence
--> Before 2003 when
human genome was
completed scientists
had to use sophisticated
method such as
screening DNA
libraries to clone
human genes
138
Many human disease genes were mapped & cloned using
positional cloning
139
How to study gene function once you
identified and cloned the gene?
* Create gene knock-out in a model organism
OR
Use transgenic technology to create transgenic
model organism
* Express recombinant protein (Insulin)
* Reveals properties of the gene
* Reveals where & when the gene is active
140
what is a gene knock-out
removing gene from the organism and see what happens --> reveals the purpose of the gene
141
what is transgenic technoloy
introducing foreign gene to the organism this reveals the properties of the gene and where and when the gene is activated
142
what can transgenic technology express/reveal
-express recombinant protein (insulin)
- reveal properties of the gene
-reveals where and when the gene is active
143
To create knock out mouse scientists first create
mouse embryonic stem cells harboring desired gene mutation (knock out)
144
what is a knock out mouse
A knockout mouse is a genetically engineered mouse in which one or more specific genes have been "knocked out" or intentionally inactivated, making them nonfunctional.
145
Since knock out mouse technology was developed in 1980...
thousands of human genes were knoched out in mice
146
Steps to create knock mouse
-target ES cells are injected into blastocysts which are implanted into foster mothers which give birth to chimeric mice --> mating between chimeric mouse and normal mouse create knock out
147
The phenotype of a knock out mouse reveals
the purpose of the unmated gene
148
Introducing foreign genes into genomes creates...
transgenic organisms
149
introduced gene into forign genome is called...
transgene
150
expression vectors are ...
specialized cloning vectors that contain regulartory sequences so that inserted trangenes will be expressed in the target organism
151
ex example of a typical expression vector is ...
E coli where we see an E.coli expression vector with
the human insulin
cDNA inserted into the
cloning site
152
Expression vector is a
vector with a
promoter
to direct expression of
insert in a particular
host organism
153
What was the first human gene to be expressed in E coli
an insulin gene
154
the bacterially expressed human insulin can be given to
diabetic patients
155
the bacterially expressed human insulin is better and ...
cheaper than getting insulin from pigs (where it used to come from)
156
some exampled of using genetic engineering for protein therapy
recombinat Human Insulin for treating Type 1 Diabetes
Recombinant Human Factor V111 for treating Hemophillia A
Recombinat Growth Hormone for treating dwarfism
157
where did human factor V111 come from before expression vectors
donated blood
158
where did growth hormone come from before expression vector
cadavers
159
Animal transgenes typically ....
integrate into the genome
160
what are the type types of transgenesis
random transgenesis
targeted transgenesis
161
what is random transgenesis
--> transgenes integrate into random locations of the genome
-no homology between the introduced DNA and the site of insertion required
162
What is targeted transgenesis
-transgenes intregrate into specific landing sites
-requires extensive homology between the introduced DNA and the site of insertion in the genome
163
How are transgenes introduced into animal model organisms?
via needle injection, electroporation or viral infection
164
Transgenes reveal the ...
properties of the gene
165
eyeless or Pax-6 is a ...
conserved gene which is essential for eye development in flies, mice and human
166
expression of mouse eyeless in Drosophila induced...
ectopic eye development in legs and antennae
167
the experiments surrounding the eyeless gene suggest that
eyeless gene is a master control gene for eye developement in all animals
168
Reporter Transgenes are used to investigate
gene regulation
169
Regulatory sequences for a gene of interest are fused
to the reporter gene, which will then be expressed in the pattern dictated by the regulatory sequences
170
how can you visualize the reporter gene expressiion-->
β-galactosidase from E. coli -> blue precipitate with X-Gal
Green Fluorescent Protein (GFP) from jellyfish*
Red Fluorescent Protein (RFP) from sea anemones*
171
Reporter transgenes reveal
where and when genes are active
172
CRISPR/ Cas 9 has the ability to...
change or edit the DNA of organisms (delete, insert, replace parts of DNA)
173
Bacteria has a ...
immune defense system against phages
174
CRISPR is a
bacterial immune system that recognizes and cuts the DNA of an invading bacteriophage
175
CRISPR stand for
clustered regularly interspaced Short Palindromic repeats in the bacterial genome
176
Scientists immediately suspected that these spacers in CRISPR are used by
bacteria to recognize invading phage viruses that bacteria has “seen” before
177
SPacers are
unique sequences that were acquired from invading phage viruses
178
CRISPR repeats ...
transcribe into pre-crRNA and cut into short
crRNAs
179
CRISPR locus also expresses
a tracrRNA and a DNA cutting enzyme called Cas
180
Bacteria uses CRISPR to recognize
invading phage viruses that bacteria has “seen” before
181
Charpentier and Doudna hypothesized that if you mix together....
Cas9 and crRNA it can be used as programable DNA cutter.
182
CRISPR allows scientists to
cut DNA at any gene or specific location of the genome of choice
183
Main advantage of CRISPR/CAS9 over restriction enzyme
Restriction enzyme can only cut that sequence that occurs every 2000 base pairs
CRISPR= You can cut any sequence you want almost anywhere you want --> Can also introduce any DNA modification of choice (deletion, insertion, replacement)
Can rewrite sequences
184
With CRISPR you can introduce any
DNA modification of choice
(deletion, insertion, replacement)
185
CLassic Knock out technology in mouse ES cells is very
inefficient --> For many loci you have to screen 1000s of clones to
get one clone with targeted mutation!
186
For CRISPR/Cas9 it is common to have what percent efficiency
90%
187
CRISPR/Cas9 system is easy to use bc to cut DNA at specific genome location you just need
short complementary crRNA
188
CRISPR/Cas9 editing is more
efficient, easier to use and is also faster in generating knock-out mice
189
ES cell targeting takes how long for a knock out mouse
1 year
190
CRISPR takes how long for knock out mouse
1-2 months
191
Why CRISPR/Cas9 revolutionized biology?
We could already introduce mutations
before
A.CRISPR/Cas9 is more efficient and is
easy to use
B. CRISPR/Cas9 is safer to use
C.Because they gave a Nobel prize for it
D.CRISPR/Cas9 does not have off-targets
(cutting in the wrong place)
A.CRISPR/Cas9 is more efficient and is
easy to use
192
With CRISPR we can swap DNA between species -> CRISPR technology enables what type of studies
evolution studies think serpentized mouse
193
CRISPR enables genome editing in ___________ in which it was simply not possible before
exotic animals
194
Crisper also benefits ....
AGRICULTURE ex--> leaver pics, no browning mushrooms, and improved crops
195
How CRISPR-based sickle cell treatment
works?
hematopoeitic Stem Clls removed from patient --> crispr-cas 9 repairs mutant B globin gene and reinfusion of edited cells and engraftment in bone marrow
196
Human heritable gene editing has been
performed by
Jiankui He --> for HIV
197
why was the human heritable gene preformed by Jiankui He unethical?
A. There are other ways to prevent HIV transfer
during IVF (e.g., wash sperm)
B. Mosaic embryos won’t prevent HIV enterance
C. Potential off-target mutations
D. Mother was given a misleading consent form
