MtC Block 3 Flashcards
(331 cards)
1
Q
Progeria
A
Premature aging, associated with shortened telomeres
2
Q
Maternal non-disjunction causes _________.
A
Down-Syndrome - Trisomy 21
3
Q
Mosaic down syndrome can be caused by
A
Mitotic non-disjunction - affections phenotype
4
Q
Trisomy 13 - Patau syndrome
A
Heart defects, midline defects, malfomred forbrain - cyclops - longterm survival rare
5
Q
Trisomy 18 - Edwards syndrome
A
Severe heart defects, profound developmental delay, overlapping digits - differnet CNS wiring - most lost before term
6
Q
Telomerase is active in
A
Germ and cancer cells
7
Q
Nearly all microscopically visible autosomal aneuploidy is _________
A
Deliterious
8
Q
Turners Syndrome (XO)
A
Short, streak ovaries, heart defects, normal intellect, infertile, 99% lost before term
9
Q
Turner’s syndrome is often due to
A
Loss of male Y
10
Q
Klinefelter’s XXY
A
Feminized, low androgen, small testes, normal IQ, - difficulty w/ relationships, infertile - sperm don’t mature
11
Q
XIST
A
All females have one fuctioning X - dosage comp - a few escape
12
Q
47XYY
A
Tall, fertile, sub-average IQ, impulsive, low confidence/anxiety - CNS hardwiring change
13
Q
Male determining locus - SRY
A
One gene on Y that determines maleness - causes problems with two - 47XYY
14
Q
3 types of prenatal genetic testing
A
Amniocentesis > 16 weeks
Chorionic villus > 9 weeks - more invasive
Non-invasive prenatal testing - 5-15% fetal DNA recoverd from blood sample from mother
15
Q
Most structural rearrangements occur from
A
Double-standed breaks
16
Q
Results of deleterious mutations of autosomal chromosomes (2)
A
- Haplo-insufficiency
- Expression of recessive gene
Ex. cri-du-chat
17
Q
Repairs of DS breaks can result in (3)
A
- Ring
- Inversion
- Translocation between non-homologous chromosomes
18
Q
Pedigree analysis applies most to
A
Monogenic disorders
19
Q
Characteristics of monogenic (Mendelian) disorders (3)
A
- Determined by a single mutant gene - very speicific point mutation in coding region usually
- Rare
- Show specific patterns of inheritance
20
Q
Characteristics of complex disorders (4)
A
- Polygeneic inheritance - more than one gene locus
- Multifactorial inheritance - combo of genetic and environmental factors
- Major group of human disease
- No specific patterns of inhericance - familial clustering
21
Q
Principle of Segregation
A
Alleles segregate so that each gamete is equally likely to contain either member of the pair
22
Q
Principle of Independent Assortment
A
During gamete formation, segregating pairs of alleles assort independently of eachother
23
Q
Pedigree
A
Graphic representation of family’s interrelationhsips and health problems - focused
24
Q
Three other important things to gather for a pedigree
A
- Ethnicity
- Religious heritage
- Country of origin
25
Two reasons to use a pedigree
1. Quantify risk of developing disease for family members - family planning
2. Analysis to obtain mode of inheritance
26
In a pedigree a male is represented by a _______ and a female by a __________
1. Square
| 2. Circle
27
An autosomal dominant disase will have what distinguishing characteristics on a pedigree (4)
1. Each affected individual has an affected parent - does not skip
2. Normal offspring will have normal offspring
3. Males and females affected equally
4. Each generation tends to have an affected individual
28
An autosomal recessive disease will have what distinguishing characteristics on a pedigree (4)
1. Can skip generations - carriers
2. Males and females affected equally
3. Normal parents can only have an affected offspring if both are carriers
4. The less frequent the allele in the population - the more likely the individuals are a product of a cosanguineous marriage
29
An X-linked dominant disease will have what distinguishing characteristics on a pedigree (3)
1. Trait is never passed from father to son
2. All daughers of an affected male and normal female are affected
3. Females are more likely to be affected than males
30
An X-liniked recessive disease will have what distinguishing characteristics on a pedigree (3)
1. Never passed from father to son
2. Passed from affected grandfather to carrier daughter to all of her sons??
3. Males more likely to be affected than females
Ex. Colorblindness
31
A Y-linked disease will have what distinguishing characteristics on a pedigree (2)
1. Always in males
| 2. Passed from father to son
32
A mitochondrial disorder will have what distinguishing characteristics on a pedigree
1. If the male is affected none of the children get it
| 2. If the female is affected they all do
33
What two things must you know to use a Punnett square
1. Mode of inheritance
| 2. Parental phenotypes
34
What are two problems with obtaining an accurate pedigree analysis
1. Variable expressivity - varying severity - trouble assigning disease to family members
2. Incomplete penetrance - person with genotype does not express diesase
35
Genetic anticipation
Members exhibit progressivley earlier age of onset and increased severity w/ each generation
-Seen in disorders involving multiple repeats
36
Mosaicism
Mutation originated as a somatic mutation during embryogenesis of one of the parents
37
Considerations for mosaicism in a pedigree
1. Risk to future offspring could be the same as from an affected parent
2. Shows features of both recessive and dominant
3. Consider a parent mosaic for a dominant allele before deciding its recessive
38
De novo mutation
Spontaneously originated in parental gamete - presents as recessive - may show dominnat inheritance in next generation
39
Genetic (locus) heterogeneity
Existance of multiple genes when mutated cause same phenotype
40
Lethality (2)
1. Recessive lethal - embryonic lethal
| 2. X-linked dominant disorders - male lethality
41
Linkage analysis
Statistical method used to ID position of human disease genes relative to known genetic markers
42
Syntenic genes
Two genes on the same chromosome - close enough that they don't segregate independently
43
Lod Score Method
1. Log (Probablity assuming linked)/(Probability assuming not linked) >3 indicates linkage > -2 indicates not linked
44
________________ works better in conjucntion with linkage analysis.
Whole genome appraoch. Better if you have genomes from multiple family members
45
Personalized medicine can (3)
1. Help with genetic predisposition, early diagnosis
2. Pharmacogenetics - drug dosages
3. Predict outcomes
46
On average human DNA differs between individuals by ____?
.1% - majority are single base changes
47
SNP
Single nucleotide polymorphsim
48
_____ is the most common variation in human genome
SNP
- inversino/deletion
- block
- copy number - identical sequences repeated on some chromosomes, not others
49
Genetic markers
Identified physical location on a chromosome whose inhericance can be monitored
50
A genetic marker can distinguish between ____________ and determine which ____________.
2 copies of alleles; allele is inherited from parent to child
51
A __________ can ID regions that harbor disease causing mutations
genetic marker
52
Restriction Fragment Length Polymorphism
Cut the DNA with a restriction enzyme - Southern Blot - look at size of chunks
53
Short sequence length polymorphism
Short repeats of 2, 3, or 4 nucleotides - randomly disbursed thorughout genome - PCR - Southern Blot - See size variations
54
SNPs occur on average _______ and are _________.
1/1000bp; bialleleic
55
Most ____ are distribued across entire gneome and have no discernable function
SNPs
56
Types of SNPs (4)
1. Coding -synonymous - no change in aa sequence
2. Coding - non-synonymous - change aa sequence
3. Promoter - alter gene expression
4. Splice site SNP - alter RNA processing
57
Copy number variants
Relatively large duplications/deletions of specific regions 50-1Mbp
58
On average there are ____ CNV/individual
12
59
High throughput platforms allow you to...
...analyze large numbers of SNPs (300k - 1M)
60
Reverse genetics
ID a gene by positional cloning based on its molecular properties (Phenotype - gene)
61
Positional cloning
Finding a gnene of unkown function by mapping them relative to a gene/marker you can clone and walking down chromosome
62
Single gene disorder
Mutation of single gene is necessary and sufficient to cause the diseae - severity due to modifier gene
63
Triplet expansion disease
Threshold of repeats before disease occurs
| HD, Fragile X syndrome, Kennedy syndrome, Myotonic dystrophy
64
Cystic fibrosis
Deterioration of lungs, Autosomal recessive, IDed gene thru linkage analysis - RFLP to ch7
65
Cystic fibrosis transmembrane conductance regulator
Codes chloride channel responsible for salt balance - salty cellular secretions promotes bacteria build up
66
Symptoms of Huntington's Disease
Degenerative disorder of the brain with progressive dementia and uncontrolled movement
-no symptoms til puberty or middle age
67
Pedigree of Huntintons disease
Autosomal dominant w/ modifier genes,
genomic imprinting & anticipation
-when inherited from the father earlier onset and greater repeat expansion
68
Hungtintin gene
180 kb, 67 exons, protein s 3150aa
Repeats of CAG in coding region (microsatellite in coding region)
9-36 normal and 37-100 in diseased - higher repeats, the earlier age of onset
69
Epigenetics
Heritable changes affecting gene expression that do no result from alterations in DNA sequence
70
Genomic Imprinting
Epigenetic phenomenon in which the sex of the transmitting apretn determines whether particular genes are expressed in offspring or not
71
Beckwith-Wiedemann Syndrome
Methylation of imprinting control region of both gametes - turns off H19/turns on IGF2 - fetal overgrowth
72
Silver-Russell Syndrome
No methylation of ICR in either gamete - turns on H19/turns off IGF2 - fetal growth retardation
73
Prader-Willi Syndrome
Missing genes from dad - low muscle tone, short stature, cognitive disabilities - uniparental disomy (2 copies from mom) - epigenetically silenced gene from father - deletion of 15q11
74
Angelman Syndrome
Missing genes from mom - Neuro-genetic disorder w/ severe intellectual/developmental disability, sleep disturbance, seizure, usually happy demeanor - Uniparental disomy from dad - deletion of 15q11
75
What is the difference between a mutation and a SNP?
A mutation occurs in 1%
76
Transition
One purine or pyrimidine swapped for another
77
Transversion
Purine for pyrimidine - higher chance for damage
78
Each gamete has ______ de novo mutation
~75
79
Why do most mutations disappear?
Most are not in the germline and aren't passed down to offspring
80
Genetic drift
Random process by which some mutations rise in the population and others disappears - how most mutations become SNPs
81
Selection
Occurs if a mutations affects the reproductive fitness of an individual - positive helps - negative hurts reproductive success
82
Migration
Mating between two sub-populations - depends size of population over successive generations
83
_________ has lead to unique polymorphisms to different ethnic/regional gropus
Human migration
84
Hardy-Weinberg Equilibrium
Describes and predicts genotype and allele frequencies in a non-evolving population - if no evolution is occuring allele freq will remain in equilibruim
85
Assumptions of Hardy-Weinburg (5)
1. No mutation must occur - no new alleles
2. No gene flow can occur - no migration
3. Random mating
4. Population must be large - no genetic drift influencing fruqency
5. No selection can occur
86
Why did Sickle Cell Anemia depart from Hardy-Weinburg?
It conveyed some defense against malaria - postive selection
87
Linkage disequilibrium
Non-random assortment due to proximity of two SNPs
88
Haplotype
Patterns of SNP alleles on a single chromosome (haploid)
89
Does a high LD correlate to a high or low number of haplotypes?
Low - more linkage - fewer combinations
90
LD Blocks
LD does not continuously decline with distance - ∃ blocks that inform eachother - highly conserved
91
Tag SNPs
Minimum SNP set to ID a haplotype - Need ~500K tag SNPs for entire genome
92
Expect ___ haplotypes when genotyping 1000 individuals from MIlwaukee for X SNPs if in linkage equilibrium
2^x haplotypes
93
What did the HapMap project do?
Looked at 6 million SNPs and identified tag SNPs in each population - Only need to look at ~ 500k SNPs
94
Polygeneic disorders
Multiple genes with multiple phenotypes and multiple environmental factors
95
What are two characteristics of polygeneic disorders?
1. Have a genetic disposition - not Mendelian Inheritance
| 2. Variable due to environmental stresses
96
Association Studies
Test for assocaition of marker allele with the disease - look at presence of genotype w/ pheontype
97
Association studies are used to look at what type of diseases
Complex inheritance, common diseases, polygenic - Look at presence of genotype w/ phenotype - ID of associated alleles
98
Linkage studies are used to lok at what types of diseases?
Mendelian genes with high penetrance - correlate inheritance of genotype with phenotype - ID of linked region
99
Indirect association
Indirect association of each marker with a quantitative trait - frequency of allele T signficantly correlated w/ higher level of the trait
100
Common variant-Common disease model
Susceptibility to common disease is conferred by alleles that are commin the population and have modest phenotypic effect - affected indiviudals have an excess
101
What is the benefit of a genome wide association study?
Allows for search of common variants without any assumptions about their nature
102
Case control
GWAS selecting individuals from both categoreies and ID frequncy differneces between groups - Analysis by chi-square test
103
Population based study
Select indiviudals randomly from population and ID phenotypic differnces between genotype group - anlysis by t-test
104
Problems with candidate gene studies (3)
1. Replication
2. Selection of candidate genes
3. Selection of SNPs - comprehensive analysis better than analysis of individual SNPs
105
Significance in GWAS
(.05/# of SNPs) P-values must be < .5 X 10^-8
106
PPAR-γ
Nuclear hormone receptor on chr. 3 - over-expression in mice inhibits insulin release - associated with diabetes
107
Genotype quality control measures (3)
1. Testing sample duplicates - same platform/different platform
2. Blank tests - establish specificity distinguishing blanks from non-blanks
3. Comparison between observed frequency w/ HW
108
Heat Shock Serine Protease HTRA 1
Associated with wet from of age-related macular degeneration
109
Problems in complex disease genetics (4)
1. GWAS are difficult and elaborate
2. Phenotype/diseases are often heterogeneous - same clinical manifestation - differnt cause
3. Differing severity
4. Tag SNPs make ID of "true" causal mutations difficult
110
eQTL Analysis
Have there been changes in DNA that affect expression levels
111
Inbred strain
Individuals of a particular species which are nearly identical to each other in genotype due to long inbreeding
112
Quantitive Trait Loci Analysis
Cross inbred diabetes rat w/ normal rat
- F1 is normal
- F2 is combination generation - look at large panel of F2 and level of diabetes - LOD scores
113
Three structures of sperm
1. Flagellum
2. Acrosome
3. Nucleus
114
Layers around ovulated oocyte (outside to in)
Zona pellucida, PM, cortex, and cortical granules
115
Ovulations occurs from the _______. The oocyte is surrounded by __________ and __________.
1. Stigma
2. Follicular fluid
3. Cumulus cells - critical for oocyte pick up
116
Genetic abnormalities in gametes usually occur during _______________.
Gametogenesis
117
Ideally, fertilization occurs in the _________.
Ampulla - early part of fallopian tube.
118
Journey of sperm thru male reproductive tract
Testes, epididymis, vas deferens, urethra
119
Barriers to sperm in the female (4)
1. Low pH
2. Sperm antibodies
3. Cervical mucosa
4. Travel up wrong fallopian tube
120
Journey of ovulated oocyte
1. Oviduct moves up around ovary to capture cumulus mass
| 2. Oviduct has cilia to move oocyte and peristaltic contraction when it's in the ampulla
121
Capaciation
Sperm membrane changes, increased metabolism, hypermotility - sense temp gradient
122
Acrosome Rx
1st thing that happens right before sperm encounters cumulus mass - fusion btw cell membrane and outer acrosome - vesicles are shed - exposes enzymes
123
What receptor do sperm bind to?
ZP2 - sperm membrane protein is SED
124
Sperm-oocyte fusion occurs at the ________ region of sperm.
Equatorial
125
What proteins does a sperm need to fuse with an oocyte?
Feritlin B, IZUMO
126
What proteins does an oocyte need to fuse with a sperm?
Integrin, CD9
127
Polyspermy preventing reactions (3)
1. Ca++ Oscillation
2. Activates cortical granules - release into perivertellen space
3. Cross link zona pellucida proteins
128
What happens immediately after a sperm enters an oocyte (3)
1. Polyspermy preventing reactions
2. Resume meiosis of oocyte (MII metaphase)
3. M and F pronuceli form metaphase plate - zygote!!
129
What stage of IVF has the highest risk of failure?
Embryo transfer
130
At what stage are the embryos transferred to uterus?
The 4-8 cell stage
131
Preimplantation genetic diagnosis
Taking away one cell does not inhibit development or damage embryo
132
What main things happen during the embryonic period? (4)
1. Form body plan - 3 layers & 3 axes
2. 3 layers create 4 tissues - organs and organ systems
3. Segmentation, head, limb and trunk formation
4. Embryo folding
133
What two main things happen during the fetal period?
1. Growth and maturation
| 2. Continued development of some systems
134
What weeks make up the embryonic period?
Week 1-8
135
What weeks make up the fetal period?
Week 9-38
136
What is the difference between the fertilization age and the gestation age?
The fertilization age is the age of the embryo where gestational age starts from the last menstruation
137
What main events occur during Week 1? (3)
1. Fertilization
2. Cleavage - Blastocyst formation
3. Implantation initiated
138
Cleavage and formation of the blastocyst is controlled by what?
Maternal RNAs
139
The nucleus from an early cleavage state _________ is capable of generating a whole embryo.
Blastomere
140
The morula is formed at the 8-cell stage via __________ and the blastocyst is formed via ___________.
1. Compaction
| 2. Cavity formation
141
Cavity formation in a blastocyst forms the ____________ and the _________________.
Inner cell mass and outer cell mass
142
What is the result if nondisjunction occurs during an early cleavage?
Mosaic embryo
143
The outer cell mass forms the _____________.
Trophoblast
144
Trophoblast formation is an example of _____________.
Genomic imprinting - requires expression of unknown parental derived alleles
145
The ICM remodels to form the ____________.
Bilaminar disc (epiblast and hypoblast)
146
What will the hypoblast make?
Will make extraembryonic membrane - primitive endoderm
147
What will the epiblast make?
Will make the embryo - primitive ectoderm
148
What is the function of the ZP?
1. Keeps blastomeres together
2. Immunological barrier
3. Prevents premature implantation
149
How does the embryo shed the ZP?
Trophoblasts produce an enzyme to help it hatch out
150
Cleavage stage embryos have the potential for regulation. Define regulation.
The ability of an embryo to produce a normal embryo when parts have been removed or added.
151
What mediates the cell diversity in the blastomere? (4)
Cell position, number of divisions, cytoplasmic determinants, and cell-cell interactions
152
What is the difference between terminal differentiation and post-mitotic cells?
Terminally differentiated cells can not become anything else, some are post-mitotic - neurons & some are not - cells lining GI
153
Stem cells
Differentiated cell that retains some pluripotent capabilities
154
Gene expression is patterned, it occurs at different levels, along specific axes, is the result of ___________ mediated by ______________.
Gene expression, transcription factors
155
HOX genes
Differential expression of HOX is how patterning during development is developed
156
How are dizygotic (paternal) twins formed?
Two ovulation and two fertilizations
157
How are monozygotic twins formed?
Early or late cleavage - 65% at blastocyst stage
| 35% at two cell stage (between blastocyst and morula) - two embryos and two implantations
158
How are conjoined twins formed?
Monozygotic twins divide after formation of embryonic disc
159
What three main things have occurred at the end of week 2?
1. Complete implantation
2. Formation of bilaminar disc - amnion and umbilical vesicle
3. Formation of additional extraembryonic mesoderm
160
Implantation occurs between days _______
5-12
161
The decidual reaction of the attachment phase of implantation involves
1. Trophoblast binds to endometrium - forms of compact layer of endometrium - makes mass of cells for implantation of embryo
162
The 2 phases of implantation are
1. Attachment - receptor mediated
| 2. Penetration and embedment into compact layer
163
Phase 2 - Penetration and embedment - of implantation is characterized by what?
The formation of the syncytiotrophoblast
164
What are four characteristics of the syncytiotrophoblast?
1. No cell boundaries - lots of nuclei
2. Mediates invasion of endometrium - more is formed as embryo embeds further
3. Microvilli on surface help it incorporate nutrients
4. Lacunae (spaces) are formed for blood and glandular secretions
165
At 12-14 days the embryo is ________ ________.
Completely embedded
166
What is the most common cause of spontaneous abortions in the first three weeks?
Chromosomal abnormalities
167
Placenta previa
Implantation occurs too close to the cervix
168
What is the most common site of extrauterine pregnancy?
Outer 1/2 of oviduct
169
Amnion
Extraembryonic membrane formed from epiblast - Surrounds embryo by Week 8
170
What is the function of the amnion?
1. Creates a space for amniotic fluid
2. Protects embryo and allows for symmetrical growth
3. Allows for proper growth of lung
4. Allows for movement
5. Assists in fluid homeostasis
171
Umbilical Vesicle (Yolk sac)
Exocoelomic membrane formed by hypoblast - bounded by extraembryonic membrane
172
What is the function of the umbilical vesicle?
1. Metabolism and transfer of nutrients from trophoblast to embryo
2. Site of initial blood and vascular formation
3. Primordial germ cells and hematopoiesis appear in wall
4. Portions may become primitive gut
5. Positions site of gastrulation - primitive streak
6. Controls epiblast cell migration
173
Extraembryonic mesoderm
Coats the inside of the trophoblast and outside of amnion and UV.
174
Mesenchyme
Free cells, non-polar, motile
175
Where does the extraembryonic mesoderm originate?
From exocoelomic membrane by delamination of cells - epithelial-mesenchymal transformation
176
Chorion
Extraembryonic mesoderm and trophoblast
177
Connecting Stalk
Bridge of extraembryonic mesoderm between chorion and embryo
178
What are 4 main things that happen in week 3?
1. Establish 3 primary germ layers
2. Beginnings of organogenesis
3. Embryo begins to fold - neural tube growing so fast it can't remain a disk
4. Establishment of asymmetry
179
Conceptus
Embryonic disc and chorionic sac
180
The trilamiar disc is formed via __________.
Gastrulation
181
Primitive Streak
Transient thickening of epiblast with a midline groove - converging epiblast cells
182
The first cells that pass the the PN form ______________, other cells pass thru and move to the opposite end of the disc to form ______________, the 2nd cells to pass thru the PS form _________________.
1. Definitive endoderm - replaced hypoblast
2. Prechordal plate (endoderm)
3. Intraembryonic mesoderm - between endoderm and epiblast
183
Epithelial-mesenchymal cell transformation occurs at ________________.
The primitive streak.
184
What is the ectoderm formed from?
Cell leftover from gastrulation
185
Primitive Node
An expansion at the cranial end of the primitive streak - also a side of E-M transformation
186
What axis does the primitive node establish?
Cranial and caudal
187
How is the notocord formed?
Cells from prechordal plate invaginate thru PN - migrate cranially, they join up with the endoderm temporarily - help form the neural tube
188
The primitive streak regresses, is restricted to the _____ and forms the ____________.
Tailbud, caudal eminence
189
At what two points of the embryo is there no mesoderm?
1. Oropharyngeal membrane cranially
| 2. Cloacal membrane caudally
190
Allantois
Diverticulum of umbilical vesicle - signaling center, becomes part of median umbilcal ligament
191
Teratoma
Neoplasm of multiple cell types - usually sacrococcygeal - most common tumor of newborns
192
What causes a teratoma?
Part of the primitive streak that didn't disappear
193
Caudal dysgenesis
Abnormalities of lumbosacral spine, lower limbs and urogenital system
194
What genes establish the cranial-caudal axis?
Otx2, Lim1, Hesx1
195
What genes establish the dorsal ventral axis?
Chordin, noggin, follistatin
196
What establishes bilateral symmetry?
The notochord
197
What establishes asymmetry L/R axis?
PN gene expression - Lefty 1, Lefty 2
198
Situs inversus
Lefty 2 misexpression on the right
199
Gastrulation
Three primary germ layers formed
200
Neurulation
1. Formation of neural plate - day 17
2. Neural plate cells get taller
3. Neural folds elevate - neural groove formed
4. Neural folds fuse
201
Neural crest
Mesenchyme derived - separate from tube jsut be fore fusion - Precursor for 1˚sensory neurons, PNS sheathing cells, neurons of autonomic ganglia, adrenal medulla, and pigment cells
202
Ectoderm will become
epidermis, CNS, parts of eye, ear, and sense of smell
203
Mesoderm will become
Organs, sk. muscle etc
204
Endoderm will become
Internal tube of GI, Resp, part of UG
205
Paraxial mesoderm will become
Sk. muscle and vertebral column
206
Intermediate mesoderm will become
Kidneys, gonads, and UG
207
Lateral mesoderm will become
Split
208
Paraxial mesoderm is segmented in the trunk and forms _______.
Somites
209
How are somites formed?
Mesenchyme aggregation and separation of somite pairs is mediated by segmentation clock and wave model
210
What patterns the somites along the cranial-caudal axis?
Homeobox Genes
211
Intracellular Ceolom
Splits lateral mesoderm - Somatic and Splanchnic Mesoderm
212
Somatic Mesoderm
Associates with ectoderm - body wall, limbs, epithelium and connective tissue of parietal layer lining body cavity
213
Splanchnic Mesoderm
Associates with endoderm - GI organs, reproductive
214
What does folding in the transverse plane yield?
Tubular embryo - outer tuber - ectoderm ; inner tube - endoderm - Also the body plan
215
What does folding in the sagittal plane yield?
C-shaped embryo - embryo lifted into amniotic cavity
216
Result of folding (3)
1. Establishment of body form
2. Structures relocated from dorsal wall to ventral wall
3. Closure of ventral body wall
4. Embryo elevated into amniotic cavity
217
Characteristics of embryo at week 4
1. Heart is beating
2. Embryonic circulation is established and connected to the yolk sac and placenta
3. Neural tube is most closed
4. Folding has begun
5. Somites continue to form
6. Embryo is 2mm long
7. Chorionic sac is 2mm in diameter
218
Gastroschisis
Intestinal tract is out to side of umbilical cord - 10% are stilborn
219
Emphalaceal
Intestinal tract comes out thru umbilical cord covered by a membrane - harder to fix
220
Throachoabdomanoschisis
Ventrothorasic and ventroabdominal wall didn't close - organs outside body
221
Failure of ventral body wall to close can result in which three anterior body wall defects?
1. Gastroschisis
2. Emphalaceal
3. Throachoabdomanoschisis
222
What are the pleuropericardial folds formed by and what do they contain?
Growth of septum from body wall
| Contains a few veins and the phrenic nerve
223
Pericardio-peritoneal canals
Connect pleural cavity and peritoneal cavity
224
What is the diaphragm composed of? (3)
1. Pleuroperitoneal folds - diaphragm
2. Septum transversum - liver
3. Dorsal mesentery of esophagus - crura
225
What is the primitive node?
Signaling center at the cranial end of the primitive streak. Forms at day 16.
226
What is the prechordal plate?
An area of mesoderm caudal to oropharyngeal membrane and cranial to the notochord - important organizing and signaling center for head development
227
Mesenchymal-Epithelial Transformation
Cells lose cell processes, become polarized, and develop cell junctions that enable them to form a layer or sheet.
228
Anterior Ventral Endoderm
An area of endoderm located at the cranial most margin of bilaminar disc - prior to gastrulation - determines head
229
Describe the clock and wave model of signaling
1. Segmentation clock - negative feedback of notch signaling
2. Wave - gradient of Fgf8 expression that regulates the competence of paraxial mesoderm cells to respond
230
Intraembryonic coelom
Space within lateral mesoderm
231
What do hemeangioblasts form?
Lining of the vascular system and blood cells
232
What happens in Week 4? (3)
1. Embryo folding
2. Appearance of limbs and pharyngeal arches
3. Beating heart
233
What is the Critical Period and when is it?
The time when the embryo is most sensitve to external insult is between the 3rd and 8th week
234
Besides HOX, what are two other families of genes that mediate patterning in the embryo?
1. Paired Box (Pax)
| 2. POU genes
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What happens in Week 4? (3)
1. Embryo folding
2. Appearance of limbs and pharyngeal arches
3. Beating heart
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What is the Critical Period and when is it?
The time when the embryo is most sensitve to external insult is between the 3rd and 8th week
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Besdies HOX, what are two other families of genes that mediate patterning in the embryo?
1. Paired Box (Pax)
| 2. POU genes
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What are four things associated with increased incidences of birth defects?
1. Increasing parental age
2. Season of the year when the child is conceived
3. Country of residence
4. Familial tendencies
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What percentage of babies will be born with a clinically significant (major) birth defect?
2-3%
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What causes birth defects (4)
1. Genetic - 13-15%
2. Environmental 7-10%
3. Multifactorial 20-25%
4. The rest are unknown 50-60%
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What are four things associated with increased incidences of birth defects?
1. Increasing parental age
2. Season of the year when the child is conceived
3. Country of residence
4. Familial tendencies
242
What is a defect or malformation and give an example
A morphological abnormality from abnormal developmental mechanisms - cause is intrinsic to development can be inherited i.e. dysplasia
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What is a disruption?
A morphological abnormality resulting for a breakdown or interference with an originally normal development process - chemicals/drugs/infections - extrinsic factors
244
What is a deformation?
The abnormal form, shape, or position of a normally formed body part - caused by mechanical forces - can sometimes be reversed
245
Polytopic field defect
Pattern of anomalies derived from a disturbance o f a single developmental field
246
Normal variation
Morphological variation of a structure is a predictable variance - i.e. branching pattern, extra muscle belly
247
A syndrome
Patterns of multiple anomalies that are seen together and are thought to have a common cause - differs from a polytopic field
248
An association
A statistically significant, non-random occurrence of two or more individuals of multiple anomalies
249
Normal variation
Morphological variation of a structure is a predictable variance - i.e. branching pattern, extra muscle belly
250
Polyploidy
3n, 4n, etc
251
Teratogen
Any agent that can produce a congenital anomaly or raise the incidence of an anomaly
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What are the five major classes of teratogens?
1. Infections - Rubella
2. Ionizing radiation and other physical agents
3. Drugs and chemicals - thalidomide, alcohol
4. Imbalance of essential metabolites and hormones - Congenital adrenal hyperplasia
5. Maternal factors - illness, T2D, smoking
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Teratology/Dysmorphology
Branch of science that studies the causes, mechanisms, and patterns of abnormal development
254
What are the major principles that describe how teratogens affect development? (5)
1. Susceptibility is dependent on age of embryonic development
2. Activity is most sensitive during periods of organ/structure development
3. Genotype of embryo and mother can modify susceptibility
4. Degree depends on dose and duration
5. Effects are due to specific mechanisms
255
What is on the A-list of drugs that cause birth defects?
Antibiotics, Anti-nauscants, anticoagulants, alcohol, anti-anxiety agents, antiHTN, antipsychotic, androgenic steriods
256
What is the defining characteristic of pluripotent stem cells?
Ability to generate all cell types of the body or form an entire organism
257
Where do embryonic stem cells come from?
Derived from inner cell mass of blastocyst - preimplantation stage embryo
258
What 2 methods can be used to produce pluripotent stem cells from differentiated cells?
1. Somatic cell nuclear transfer
| 2. Direct reprogramming
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How would you describe the potential of a mesenchymal stem cell?
Multipotent - osteoblasts, chondroblasts, and adipocytes
260
What is the main role of resident stem cells?
Primarily involved in tissue homeostasis and repair
261
What stage is the embryo in during the initial stage of implantation?
Bilaminar disk - epiblast and hypoblast
| Trophoblast - mitotically active when it attaches - syncytiotrophoblast
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Functional Zone
Outer 2/3 of the thickness of the endometrium - participates in cyclic changes of menstrual cycle - Implantation occurs here
263
Basal Zone
Inner 1/3 of endometrium adjacent to myometrium - generate new functional zone each menstrual cycle
264
What stage is the embryo in during the initial stage of implantation?
Bilaminar disk - epiblast and hypoblast
| Trophoblast - mitotically active when it attaches - syncytiotrophoblast
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Where is hCG secreted and what is its role?
By the syncytiotrophoblast - rescues corpus luteum until the placenta can take over production of estrogen and progesterone
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Decidual reaction
1. Stromal cells become enlarged - Compact layer
2. Enlargement of glands and the decidual cell thickens endometrium
3. Blood flow is increased
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Which zone of the endometrium participates in the decidual reaction?
The Functional zone?
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What are the layers of the decidua from the embryo out
Decidua basalis - adjacent to embryo
Decidua capsularis - surrounds chorionic sac
Decidua parietalis - remainder of uterine endometrium
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Primary chorionic villi
Little fingers of cytotrophoblast that extended into the syncytiotrophoblast toward the endometrium
270
Secondary chorionic villi
Occurs when extraembryonic mesoderm forms a central core - days 12-20
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Tertiary/Mature chorionic villi
1. Vascular precursor ells of extraembryonic mesoderm form a primitive vascular network within mesodermal core of villi
2. Connect with the vascular network in chorion
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What components of mature chorionic villi are formed in the placenta
1. Stem villi - central core/tree trunk
2. Intermediate (floating) villi - branches
3. Terminal Villi - leaves - contain sinusoids - exchange happens here
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Chorionic plate
Chorion that forms the wall of the chorionic sac - stem villi are rooted here
274
Cytotrophoblastic Shett
Extension of cytotrophobast from stem villus that join together - anchors the chorionic sac to the endometrium
275
Chorion Laeve
The chorionic villi formed in the disidua capsularis disappear as the chorion gets thinner w/ growht of fetus - smooth leftover layer
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Chorion Frondosum
Chorion adjacent to the decidua basilis
277
Umbilical vessels
Connects vasculatures of the embryo to the chorion
278
Vascular formation in Week 4
1. Vascular system of embryo is connected to the vasculature of chorion as well as the yolk sac
2. When blood vessels appear in embryo circulation becomes intraembryonic
279
Viteline vessels
Vessels connecting the vasculatures of the embryo to the yolk sac
280
Umbilical vessels
Connects vasculatures of the embryo to the chorion
281
In the placenta the chorionic villus trees are surround by intervillous spaces containing ____________. The _______________ deliver ________________.
1. maternal blood
2. endometrial arteries
3. blood to the intervillous space
282
What constitutes the placental barrier in the 1st trimester? (6)
1. Syncytiotrophoblast
2. Cytotrophoblast
3. Basement membrane
4. CT of villi
5. BM
6. Sinusoid endothelmium
283
What constitutes the placental barrier in the 3rd trimester? (4)
1. Think layer of syncytiotrophoblast
2. CT
3. BM
4. Sinusoid endothelium
284
After 4 months of development what changed occur in the placenta?
The syncytiotrophoblast thins and the cytotrophoblast begins to disappear
285
What is the difference between the fetal face and the maternal face of the placenta?
1. The fetal side is the shiny side - chorioamniotic membrane - placental blood vessels converging into umbilical vessels
2. Maternal side is the muddy side - cotyledons are visible
286
Cotyledon
Mature 3˚chorionic villus separated by placental septa
287
Placental septa
Partition of placental tissue separating adjacent intervillous spaces
288
What substance can cross the placenta?
Gasses, ions,glucose, proteins, hormones, some drugs, infectious agents, EtOH
289
How do proteins and larger molecules cross the barrier?
Via endocytosis or pinocytosis
290
What does the placenta produce?
1. Steroid, peptide, glycopeptide hormones
2. Placental proteins
3. Can make glycogen, cholesterol, and FA
291
What factors prevent the mother from rejecting the fetus?
1. Absence of paternal-derived histocompatibility antigens on the surface of the syncytiotrophoblast
2. Selective suppression of maternal immune system
3. Creation of immunologically privileged site by decidual reaction
292
Basal plate
Formed by the deciuda basalis (functional zone) and chorionic tissue
293
Placental base
Basal zone next to placenta - remains to form new functional zone
294
Placental abruption
Unexpected hemorrhage can mediate premature separation of the placenta - blood acts like a wedge that separates the placenta from the uterus
295
What can cause placental abruption?
1. Smoking
2. Maternal malnutrition
3. Hypertension
4. Trauma
5. Drug abuse
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Molar pregnancy
Only paternally-derived DNA is present in trophoblastic tissue (genomic imprinting)
297
What is an indicator of a molar pregnancy
Abnormally high hCG
298
Placental accreta
Implantation extends into basal zone - separation is impossible - otherwise it becomes cancerous
299
Velamentous cord insertion
Umbilical vessels extend into chorioamniotic membrane
300
Field defect
Pattern of anomalies derived from a disturbance of a single embryonic field - midline, tailbud region - rare
301
Syndrome
Pattern of multiple primary anomalies which are seen together and causally related - fetal alcohol syndrome
302
Sequence (defect)
Pattern of anomalies which results from a single primary anomaly - insufficient amniotic fluid - compressed facial features
303
Chronic granulomatous disease
Inherited NADPH oxidase deficiency - infections
304
Reperfusion injury
Ischemia - resumption of blood flow causes damage - inc. hypoxanthine and inc. xanthine oxidase - increased formation of oxygen-derived radicals
305
How do you treat a reperfusion injury?
Allopurinol, antioxidant enzymes, iron chelators
306
How do you form singlet oxygen?
Photosensitive dye - oxygen with empty orbital - very short lived oxidizes target very quickly
307
Photodynamic therapy
Using singlet oxygen to selectively bind dye to tumor - localized light delivery
308
Cutaneous porphyria
Defective heme synthesis - accumulates in skin - sun causes skin blistering/swelling due to formation of singlet oxygen
309
Peroxynitrite
Potent oxidant - reacts with lipid, protein, and DNA - also removes NO required for vasodilation
310
NO synthase
L-arginine, NADPH, O2, (cofactors: calmodulin, Ca, and BH4)
311
LNAME and LNMMA
Inhibit NO
| LNAME - nonspecific
312
Inhibitors of BH4 synthesis will _______ nitric oxide biosynthesis
Inhibit
313
NADPH oxidases
Generate superoxide and hydrogen peroxide - only known function
314
NOX1 etc.
(NADPH Oxidase) Multi-enzyme complex - different types
315
Inhibition and interception of ROS and RNS (3)
Small molecular weight antioxidants (vitamin E, C glutathione)
2. Antioxidant gene expression (heme, glutathione syn)
3. SOD - not completely detox - reduces superoxide
316
Catalase
Reacts with hydrogen peroxide - use in conjunction with SOD
317
Glutathione peroxidases
Removes hydrogen peroxide - uses up one NADPH - pentose phosphate pathway
318
Small Molecule Antioxidants (4)
1. Vitamin C
2. Vitamin E
3. Glutathione (GSH)
4. Beta-carotene
319
Cross talk between lipophilic and hydrophilic antioxidants
Vitamin E is lipophilic - Vitamin C is hydrophilic
| Vitamin E radical is recycled back to Vita E by reacting w/ ascorbate at the surface
320
Oxidative stress
Imbalance between prooxidant and antioxidant levels - favoring prooxidants
321
Oxidative damage
Modification of lipids, proteins, DNA
322
When will antioxidant therapy work?
Kwashiorkor (low levels of glutathione) - chronic inflammatory conditions - iron overload - vitamin deficiency
323
Lipid peroxidation
Associated with atherosclerosis - cycle can go on and on - need terminating reaction i.e. Vitamin E
324
Keap1-Nrf2-ARE pathway
ROS activate this pathway to transcribe more antioxidant genes (SOD, Heme oxygenase)
Nrf2 = TF
325
Curcumin
Activates Keap1-Nrf2 pathway
326
Mitohormesis
Links physical exercise and formation of ROS to insulin sensitivity and antioxidant defense
327
Adverse side effects of chemotherapy (doxorubicin)
From ROS/RNS - cardiomyopathy years later
328
What is the cause of cardiotoxicity with doxorubicin use?
Mitochondrial DNA damage, protein oxidation, lipid peroxidation (From Fe + H2O2)
329
What is given to avoid doxorubicin toxicity?
Iron chelators and vitamin E
330
Cisplatin
Chemotherapy - nephrotoxicity - DNA damage, inhibits DNA repair - increases NOX, iNOS
331
Cisplatin
Chemotherapy - nephrotoxicity - DNA damage, inhibits DNA repair - increases NOX, iNOS
