George Mason University Biology and Familiar Genetics Questions I have a genetics test and it is going to be 25 questions mostly multiple choices. I need t

George Mason University Biology and Familiar Genetics Questions I have a genetics test and it is going to be 25 questions mostly multiple choices. I need to work with someone major in biology and familiar with genetics course. ( the test it is only 50 minute)I have attached all the lecture slides for the test, please go over themI will start taking the test when are you ready and will copay and paste the questions here in the chat to answer.Thank you Cell Division
Part 1: Mitosis
CHAPTER 2
Lecture Presentation by
Dr. Cindy Malone,
California State University Northridge
Cellular Reproduction
The ability to reproduce is a fundamental
characteristic of life:
Cells divide when:
• an organism grows
• an organism becomes damaged and needs to produce
new cells
Cell Division
It is essential that any new cells produced contain genetic
information that is identical to the parent cell:
• How cell division (and thus tissue growth) is controlled is
very complex.
• Cancer occurs where regulation of the cell cycle goes wrong
and normal cell growth and behavior is lost.
Cell Division
Mitosis leads to production of two identical cells:
• Each with same number of chromosomes as parent cell
• Mitosis Partitions Chromosomes into Dividing Cells
Meiosis leads to production of four non-identical gametes
Cell Division: Mitosis v Meiosis
Mitosis leads to production of two identical cells
• Each with same number of chromosomes as parent cell
• Mitosis Partitions Chromosomes into Dividing Cells
Meiosis leads to production of four non-identical gametes
Cell Structure Is Closely Tied to
Genetic Function
There are two main types of
cells:
• Prokaryotic (bacteria, archaea)
• Eukaryotic (protists, plants,
fungi, animals)
All cells share some common
features:
• Plasma membrane
• DNA
• Ribosomes
Nucleus and Nucleoid
Nucleus
◦
◦
◦
◦
Found in eukaryotes
Membrane bound
Houses genetic material, DNA
DNA: complex array of acidic and basic
proteins into thin fibers
◦ During nondivisional phases, chromosomes
uncoil into a diffuse network within the
nucleus: chromatin
Nucleoid
◦ Found in prokaryotes
◦ Not membrane bound
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Cytoplasm
Functions of the cytoplasm:
• Regulates exchange of material outside the
cell
• Biosynthesis of macromolecules
• Generation of energy
• Cell movement
Components of the cytoplasm:
• Cytoplasmic organelles
• Cytoplasmic matrix or cytosol
• Cytoskeleton made of extensive system of
microtubules (tubulin) and filaments
(actin)
Centrioles
Centrioles are complex, microtubulebased structures:
• found in animal and plant cells
• form basal bodies required for the
formation of cilia and flagella
• near the nucleus, in the cytoplasm
• the major microtubule organizing center
(MTOC) in dividing cells
• organize the spindle fibers for movement
of chromosomes during meiosis and
mitosis
Homologous Chromosomes
Chromosomes exist in homologous
pairs in diploid organisms:
• Homologous chromosomes are
chromosome pairs (one from each
parent) that are similar in length, gene
position, and centromere location.
• However, the genes contain different
alleles
Homologous Chromosomes
Homologous
chromosomes:
• Are equivalent, but not
identical
• Carry genes for the same
inherited characteristics
• May carry different versions
of the same gene
The Cell Cycle
The cell cycle is an ordered set of
events, culminating in cell growth
and division into two daughter cells.
The stages are G1-S-G2-M.
G1, S & G2 are part of interphase:
• S phase: DNA is synthesized
• Two gap phases: G1 and G2
The Cell Cycle
The M stage stands for mitosis,
and is when nuclear and
cytoplasmic division occurs:
1. nuclear division –
chromosomes separate
2. cytoplasmic division cytokinesis
The Cell Cycle
Cells send most of their time
in interphase
Composed of interphase (90-95%
of the time) and mitosis (5-10%).
G0: Point in G1 phase where cells
are nondividing, but a
metabolically active state
Sister chromatids
S phase resulted in the duplication of each chromatid.
Sister chromatids
Since there is only one
centromere on the sister
chromatids, we still call
them one chromosome
And because there are still
just 2 alleles at each locus,
the cell remains diploid (2n)
Mitosis
Mitosis partitions chromosomes into dividing cells
Mitosis (meaning ‘threads’, referring to the thread-like appearance of
the chromosomes) is basically the same in all organisms.
The Cell Cycle – Mitosis (M Stage)
There are four recognizable phases
to M stage:
•
•
•
•
Prophase (prometaphase)
Metaphase
Anaphase
Telophase
Mitosis
Stages of Mitosis
There are four recognizable phases to M
stage:
• Prophase (prometaphase)
• Metaphase
• Anaphase
• Telophase
Interphase
The cell is engaged in metabolic activity and
performing its duty as part of a tissue
The chromosomes are uncoiled and not visible
The DNA duplicates to prepare for mitosis
Interphase
The cell is engaged in metabolic activity and
performing its duty as part of a tissue
The chromosomes are uncoiled and not
visible
The DNA duplicates to prepare for mitosis
Cells have a distinct nucleus and a dark spot
called the nucleolus may be visible.
Prophase
1. The chromosomes condense (coil tightly) into
rod-shaped structures
2. The nuclear membrane dissolves and the
nucleolus dissappears
3. Proteins attach to the centromeres creating the
kinetochores.
4. Microtubules attach at the kinetochores,
centriole pairs migrate to opposite ends of the
cell and the spindle forms.
Kinetochore
Kinetochore
• Proteins associated with centromere
• Spindle fibers bind to kinetochore; chromosomes migrate
Prophase
1. The chromosomes condense
2. The nuclear membrane dissolves and the
nucleolus disappears
3. Proteins attach to the centromeres
creating the kinetochores.
4. Microtubules attach at the kinetochores
5. Centriole pairs migrate to opposite ends
of the cell and the spindle forms.
Metaphase
1. Chromosomes line up at the
equator of the spindle
2. Sister chromatids are attached to
separate spindle fibers by their
centromeres
Metaphase
1. Chromosomes line up at the
equator of the spindle
2. Sister chromatids are attached to
separate spindle fibers by their
centromeres
Anaphase
The paired chromosomes separate
at the kinetochores and move to
opposite poles of the spindle
Anaphase
Anaphase: Disjunction
1. Sister chromatids separate
2. Migrate to opposite poles
Separated sister chromatids are called
daughter chromosomes
Telophase
1. A new nuclear membrane forms
around each chromosome set
2. The nucleolus reappears
3. The chromosomes uncoil, disperse
and are no longer visible under the
light microscope.
4. Cytokinesis (partitioning of the cell)
occurs at the end of telophase and
ends with the division of the parent
cell into two daughter cells:
• Furrowing in animal cells
• Cell plate formation in plants
Telophase
4. Cytokinesis (partitioning of the cell) occurs at
the end of telophase and ends with the division
of the parent cell into two daughter cells:
• Furrowing in animal cells
• Cell plate formation in plants
The time spent in each interval of one complete cell
cycle of a human cell in culture.
© 2015 PEARSON EDUCATION, INC.
Summary of Mitosis
Mitosis:
• Partitions chromosomes into dividing cells
• Produces daughter cells with a full diploid complement
of chromosomes
• Major differences between plants & animals are in
spindle formation (animals have centrioles, plants do
not) and in the method of cytokinesis
Cell Cycle and Regulation
Checkpoints
G1/S checkpoint
• Monitors size cell has achieved
• Evaluates condition of DNA
G2/M checkpoint
• Monitors if DNA replication is incomplete
• Monitors damaged DNA
M checkpoint
• Monitors successful formation of spindle fiber system and
attachment to kinetochores
Chromosomes
• Visible only during mitosis and meiosis
• Condense during prophase
• Chromatin fibers that make up chromosomes coil and
condense in these stages
• Electron microscopy has revealed the physical nature of mitotic
and meiotic chromosomes
Folded-Fiber Model
EM of mitotic chromosomes in varying states of coiling led to
postulation of the folded-fiber model
Mitosis Videos
The whole of mitosis lasts about 30 – 60 minutes in real time, here it
is shown speeded up:


Chromosome Mapping
CHAPTER 5
Lecture Presentation by
Dr. Cindy Malone,
California State University Northridge
Linkage Mapping
Chromosomes are the unit of
transmission in meiosis, not
genes
• Linked genes do not undergo
independent assortment
because they segregate
together
• Chromosome maps: Indicate
relative location of genes on
chromosome
Family Pedigree Analysis
Genetic Cross & Pedigree
analysis:
looks for an association
between the inheritance of a
genetic marker and a trait
Crossing Over
Crossing over – the exchange of chromosomal
material between homologous chromosomes
by breakages and reunion.
• Crossing over results in recombination
• Frequency of crossing over between two
sites (loci) on a single chromosome is
proportional to distance between them
• As distance increases, the chance of crossing
over increases
Meiotic Consequences
During meiosis, a limited
number of crossover events
occur in each tetrad
These recombination events
occur randomly along the length
of the tetrad
The closer two loci are together
on the chromosome, the less
likely that any single crossover
event will occur between them.
Crossing Over and Chiasmata
Chiasmata
• Synapsed chromosomes in meiosis wrap around each other
• X-shaped intersections with points of overlap
• Points of genetic exchange
Chiasmata present between
synapsed homologs during
the prophase I of meiosis.
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Chiasma
Percentage of offspring resulting from recombinant gametes
depends on distance between two genes on same
chromosome
Two genes located close to each other along a chromosome
are less likely to have chiasma
Sturtevant and Mapping
Sturtevant
• Compiled data from crosses
• Recombination frequencies between linked genes are additive
• Frequency of exchange is estimate of relative distance
between two genes
Map Units
• 1 map unit = 1 percent chance of recombination between
two genes on chromosome
• Also called centiMorgans (cM)
• Relative distances, not exact ones
Single Crossovers
Single crossover (SCO)
• Occurs between two nonsister chromatids
• Recombination is observed in 50% of gametes
• In genes 50 cM apart, crossing over can be expected between
100% of tetrads
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Single Crossovers
Single exchange between two nonsister chromatids in tetrad stage
• Two noncrossover (parental) gametes produced
• Two crossover (recombinant) gametes produced
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Multiple Exchanges
Determining the gene sequence during mapping requires
the analysis of multiple crossovers
Single crossover
• Used to determine distance between two linked genes
Double crossover
• Double exchanges of genetic material
• Used to determine distance between three linked genes
• Genes must be heterozygous for two alleles
Consequences of a double exchange
between two nonsister chromatids
centiMorgans (cM)
Percentage of recombination is measured in units of cM
3/25 = 12% = 12 centiMorgans (cM)
Map Distance
Expected frequency of multiple exchanges between two
genes predicted from distance between them
As the distance between two genes increases, mapping
estimates become more inaccurate
Genes farther apart increase the probability of undetected
crossovers
Linkage Ratio and Groups
Linkage ratio
• Complete linkage between two genes due to close proximity
• Unique F2 phenotypic ratio results
Linkage group
• Genes on the same chromosome are part of a linkage group
• Number of linkage groups should correspond to haploid
number of chromosomes
Interference (I)
Interference: in general, if there is a crossover at one spot
on a chromosome, this decreases the likelihood of a
crossover in a nearby spot:
• Inhibition of further crossover events
• Inhibited by another crossover event nearby
• Reduces expected number of multiple crossovers
Model Organisms have been
Extensively Mapped
Large number of mutants in organisms such as:
• Drosophila
• Maize
• Mice
Allows for construction of extensive chromosome mapping
Drosophila melanogaster Genetic Map
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Positional Cloning
Allows the molecular isolation of the genes involved in human inherited
diseases, in the absence of functional information about the gene
product. Positional Cloning or Reverse Genetics involves:
1.
Finding a genetic marker whose alleles are coinherited with disease
symptoms in affected families (a “linked” marker)
2.
Generating more markers in the area to refine the genetic candidate
region through the identification of chromosomal recombinations
3.
Cloning the genomic DNA within the candidate region
4.
Isolating genes from the genomic clones
5.
Determining which gene harbors mutations that cause the disease
DNA Markers and RFLPs
DNA markers:
• Short segments of DNA with known sequence and location
• Useful landmarks for mapping
• Earliest examples of DNA markers:
• RFLPs and microsatellites
RFLPs and Microsatellites
RFLPs: Restriction fragment length polymorphisms:
• Polymorphic sites
• Generated when specific DNA sequences are recognized and
cut by restriction enzyme
Microsatellites
• Short repetitive sequences
• Found throughout genome
Huntington’s Disease
Huntingtin (HTT) was the first
disease-associated gene
mapped to a human
chromosome (1983):
• two large families with
Huntingdon’s Disease
• analyzed for the inheritance of a
restriction fragment length
polymorphisms (RFLPs) and
Huntington’s Disease (HD) in their
family pedigrees.
Huntington’s Disease (HD)
RFLP analyses of chromosomal
DNA digested with the
restriction enzyme HindIII
• Inheritance of the 4.9 kb RFLP in
HindIII-digested DNA was
associated with HD
• The RFLP had a 65:1 chance of
being linked to the HD gene in an
Iowa family of 27 members
• The RFLP had a 106:1 chance of
being linked to the HD gene in an
analysis of RFLPs in a pedigree of 75
individuals from Venezuela
Gusella et al., 1983
Huntington’s Disease
RFLP analyses of
chromosomal DNA digested
with the restriction enzyme
HindIII
• Inheritance of the 4.9 kb RFLP
DNA fragment was associated
with HD
• The 4.9 kb RFLP site was
localized to the short arm (p)
of chromosome 4
Gusella et al., 1983
Huntington’s Disease
Ten years later, scientists identified the DNA
sequence and determined that the HTT gene
contains a region where the triplet nucleotide
CAG is repeated several times.
The number of CAG repeats present in the
HTT gene determines whether an individual
will have Huntington’s Disease.
Unaffected: 6-35 CAG repeats
Increased risk: 36-39 repeats will be at
increased risk for HD
Individuals with 40 or more CAG repeats will
get the disease.
Cystic Fibrosis
Cystic fibrosis
• Gene located by using DNA markers
• Life-shortening autosomal recessive disorder
• In 1989, a gene mapped to chromosome 7:
Approx. 70% of cystic fibrosis patients have a 3 bp deletion mutation
Mutation results in the loss of a phenylalanine residue at amino acid
position 508 of a chloride channel
Cystic Fibrosis
The first Mendelian disease gene to
be cloned was the CFTR transporter
involved in cystic fibrosis in 1989:
• > 1,000 mutations in the CFTR gene have
been identified in people with cystic fibrosis
• Most of these mutations change single
amino acids in the CFTR protein or cause
deletions in the CFTR gene
• The most common mutation, called delta
F508, is a deletion of one amino acid at
position 508.
• The mutated channel breaks down shortly
after synthesis, so it never reaches the cell
membrane to transport chloride ions
Genetic & Physical Maps
Genetic & Physical Maps
Genetic maps are
based on %
recombination
Physical maps are
based on DNA
sequencing
Lod Score Method
Chromosome mapping is now possible using DNA markers
and annotated computer databases
Lod (log of odds favouring linkage) score method:
• Relies on probability calculations
• Demonstrates linkage between two genes when linkage
analysis relies primarily on pedigrees
• Assesses probability that pedigree with two traits reflects
genetic linkage between them
Modern Gene Mapping Techniques
Genome Sequencing &
Mapping: SNPs
SNPs: Single-nucleotide
polymorphisms
• Found throughout genome
• Used by geneticists to identify
and locate related genes
• Used to screen for diseases:
•
•
•
•
•
•
Diabetes
Crohn’s disease
Hypertension
Heart disease
Arthritis
Obesity
Rare Genetic Disorders (RGDs)
De novo and inherited rare
genetic disorders (RGDs) are a
major cause of human
morbidity:
• Recent advances in genomic
technologies and data sharing have
revolutionized the identification
and diagnosis of RGDs
• Several therapeutic strategies are
being developed for rare genetic
diseases
Human Genetic Diseases of
Known Molecular Basis
After the first draft of the
human genome sequence in
2001, the rate of discovery
of Mendelian disease genes
increased dramatically.
Online Catalog of Human
Genes and Genetic Disorders
Online Mendelian Inheritance in Man: https://omim.org/
Systems Affected by Single
Gene Rare Genetic Disorders
The molecular basis of
>70 % of all human
single-gene diseases, is
now known.
Reading
Chapter 2
Chapter 5
(Chapter 2.3)
(Chapters 5 & 15.1)
DNA Organization
in Chromosomes
CHAPTER 12
Lecture Presentation by
Dr. Cindy Malone,
California State University Northridge
Bacterial and Viral Chromosomes
Viral and Bacterial Chromosomes
Are Simple Molecules:
• Single nucleic acid molecule
• Largely devoid of associated
proteins
• Much smaller than eukaryotic
chromosomes
• Contain less genetic information
Viral Chromosomes
Viral nucleic acids:
• Either DNA or RNA, single or
double stranded
• Circular or linear molecules
• Viral genetic material is inert until
released into host cell
• Able to package long DNA into a
small volume, just like bacteria
and eukaryotic cells
• Bacteriophage DNA is 17 μM long
• Capsid is 0.1 μM wide
Electron micrograph of bacteriophage T2, which has had its DNA
released by osmotic shock
Bacterial Chromosome Structure
Bacterial chromosomes
• Circular, double-stranded DNA
compacted into nucleoid
• E. coli DNA is 1200 μm long
• E. coli are 2 μm wide
Bacteria DNA is associated with a few
DNA-binding proteins
• high % of positive-charged amino acids
• help to fold & bend DNA, compacting
Bacterial chromosomes are readily
replicated and transcribed
Electron micrograph of the bacterium Escherichia coli, which
has had its DNA released by osmotic shock
© 2015 PEARSON EDUCATION, INC.
Supercoiling
Supercoiling facilitates compaction of DNA:
Supercoiled DNA
• Closed-circular molecules
• More compact
Topoisomerases
Topoisomerases
• Enzymes that cut one or both DNA strands
• Wind or unwind helix before resealing ends
Supercoiled DNA and topoisomerases are found in
eukaryotes
Prokaryote and eukaryote DNA
• Replication and transcription create supercoils
downstream as double helix unwinds
Packing Problem
How is DNA packed into a
smaller nucleus?
• The length of a typical human
chromosome is ~34 mm
• All 46 chromosomes ~2 meters
long (6 feet)
• Nuclear diameter ~10 μm
Chromatin
DNA is organized into chromatin in eukaryotes
• At interphase, eukaryotic chromosomes uncoil and
decondense into a form called chromatin
• Chromatin has a large amount of associated protein
• During interphase, chromatin is dispersed throughout
nucleus
• During cell division, chromatin coils and condenses back
into visible chromosomes
Histones
Positively charged proteins associated with chromosomal DNA in
eukaryotes:
• Contain large amounts of the positively charged lysine and arginine
• Electrostatically bond to negatively charged phosphate
Five main types of histones:
• H1, H2A, H2B, H3, and H4
Nucleosomes
Nucleosomes:
• Section of DNA wrapped around 8 histone proteins
• Resemble beads on a string…
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