Exam 2 Flashcards
(120 cards)
1
Q
Autosome
A
Chr1 - Chr22
Non sex Chromosome
2
Q
Allosome
A
ChrX or ChrY
“Sex chromosome”
“gonosome”
3
Q
Hemizygous
A
X-linked genes in males
4
Q
Pleiotropy
A
When one gene affects multiple phenotypes Ex: The wolves turned dogs - Behavior - Floppy ears - Curly tails
5
Q
Incomplete dominant trait
A
The heterozygote expresses an INTERMEDIATE phenotype
Ex: Flower color
- red x white = pink
6
Q
Codominant
A
The heterozygote expresses BOTH phenotypes
ex: ABO blood typing
7
Q
Haploinsufficiency
A
A single gene copy does NOT have the ability to express the WT phenotype
8
Q
Dosage compensation
A
One ChrX stochastically inactivated in each somatic cell
This is so each cell, in males or females, only have one copy of ChrX
- Random: 50/50 chance in any cell of either ChrX (dad’s or mom’s)
- Fixed: once inactivated, all descendent cells will follow suit
- Incomplete: some regions NOT inactivated
9
Q
Barr body
A
Highly condensed Chr visible in nucleus during interphase
10
Q
Expressivity
A
The severity of expression of the phenotype among individuals with the genotype
- Result of environmental factors (sex, exposure, …)
11
Q
Penetrance
A
The probability that a gene will express a phenotype AT ALL
“Incomplete penetrance” = any penetrance under 100%
12
Q
Early stage of embryogenesis
A
- 0 to 2 weeks
- starting with fertilization
- not sensitive to teratogens b/c not connected to mom yet
- right rate of lethality
13
Q
Embryonic stage of embryogenesis
A
- 3 to 8 weeks
- period of greatest teratogen sensitivity
- organogenesis (all organs formed here)
- each organ system has its own period of peak sensitivity
14
Q
Fetal stage of embryogenesis
A
- 9 to 38 weeks
- decreasing teratogen sensitivity
- period of functional maturation
15
Q
Teratogen
A
anything that causes birth defects
16
Q
Congenital
A
Present at birth
17
Q
Malformation
A
- The tissue itself is flawed
- Etiology: genetic, teratogenic —- morphogenic error
- ex: spina bifida, myelomeningocele
18
Q
Deformation
A
- Due to extrinsic factor
- Etiology: Extrinsic (fetal constraint), intrinsic (fetal akinesia) —> abnormla force
- ex: club foot
19
Q
Disruption
A
- Normal development stops
- Etiology: vascular, compressive, tearing —> vasculor occlusion (any abnormal force)
20
Q
Trisomy 21
A
Downs Syndrome
- Extra copy of chr21
- Growth/mental retardation
- Craniofacial defects: brachycephaly, small nose, …
- Cardiac defects: in 40%, septal defects of PDA
21
Q
Trisomy 18
“18 year olds want to fight”
A
Edward Syndrome
- Mental retardation
- Clenched fists: flexion of fingers/hands
22
Q
Trisomy 13
“13 in unlucky, people spit like puh-tooy for luck”
A
Patau Syndrome
- Mental retardation
- Deafness
23
Q
Trisomy 8
“the 8 is long in the trunk”
A
Warkany Syndrome
- Mental retardation
- Long, slender trunk
24
Q
47, XXY
A
Klinefelter Syndrome
- Male
- Presence of Barr bodies
- Sterile, testicular atrophy
- Gynechomastia
25
45, X
Turner's Syndrome
- In 80% of cases, due to paternal nondisjunction
- Short stature, broad chest, short neck
- Streak gonads (gonadal dysgenesis)
- The only monosomy capable of life
26
47, XXX
Triple X Syndrome
- Female
- 2 Barr bodies
- Amenorrheic
27
Cri du chat Syndrome
| "quatre cinq sounds like 'cat is 5' "
Partial deletion of 5p (short arm)
| - Characteristic cry like a cat because of malformed larynx
28
Deletion 4q syndrome
Partial deletion of 4q (long arm)
- Cleft lip
- Limb abnormalities
29
Angelman Syndrome
"Happy Puppet Syndrome"
- Microdeletion on 15q (on the maternal chromosome)
- Puppet-like gait
- Aphasia (absent speech)
- Prone to unprovoked periods of uncontrollable laughter
30
Prader-Willi Syndrome
Microdeletion on 15q (on paternal chr)
- Obesity
- Hypotonia
- Hypogonadism
31
Miller-Dieker Syndrome
Microdeletion on 17p
- Lissencephaly (smooth brain)
- Microcephaly
- Sever mental retardation
32
Maternal imprimting
Means that mom's genes are silenced
| Epigenetic
33
Primordial Germ Cells
Arise from epiblast (Week 2)
| Give rise to all gametes
34
Monosomy
Diploid individual who has only 1 copy of a chr
35
Trisomy
Diploid individual who has 3 copies of a chr
36
Spermatogenesis Flow
```
Starting at puberty
Anterior pituitary secretes LH/FSH
---> Leydig cells secrete testosterone
---> Stimulates primordial germ cells to differentiate
---> Spermatogonia Type A
---> Spermatogonia Type B
---> Primary spermatocytes
---> Meiosis 1
---> Secondary spermatocytes
---> Meiosis 2
---> Spermatids
---> Spermiogenesis
---> Mature spermatozoa
```
37
Sertoli cells
Supporter cells of primordial germ cells in males
38
Spermiogenesis changes
- Condensed nucleus
- Formation of acrosome (enzyme-filled)
- Formation of tail for motility (flagellum)
- Formation of middle piece (mitochondria)
- Shedding of cytoplasm (polar body)
39
Oogenesis flow
All before birth
- Primordia germ cells ---> Oogonia ---> Mitosis ---> Primary oocytes (rest at Prophase 1)
At puberty, one egg selected each month
- Finish Meiosis 1 ---> Primary oocyte + polar body ---> Meiosis 2 (rest at Metaphase 2 ---> Ovulation
If fertilized
- Finish meiosis 2 ---> Mature Ova + polar body
40
Follicle
Granulose Cells
- The epithelial cells surrounding the oocyte as it goes through oogenesis
- They make a capsule
- Until puberty, they for a single squamous layer around primary oocyte
41
Folliculogenesis flow
| + Characteristics
- Primordial follicle (single layer squamous cells)
- Primary follicle (stratified cuboidal cells + zona pellucida)
- Secondary follicle (bigger, + antrum)
- Mature (Graafin) follicle (cumulus oophorus, secondary oocyte)
42
Zona pellucida
- Layer between maturing oocyte and granulose cells
| - Full of glycoprotein (secreted by both oocyte and follicle cells)
43
Antrum
- Empty space found in the maturing follicle
44
Cumulus oophorus
- The granulosa cells that exit the ovary along with the secondary oocyte during ovulation
45
Menstrual phase
- If fertilization does not occur, endometrial lining sloughs off
(requires progesterone)
46
Proliferative/Follicular phase
- As follicle develops in ovary
- Granulosa cells produce estrogen
- Causes endometrial lining to thicken
47
Secretory/Progestational Phase
- After ovulation
| - Corput luteum produces progesterone to maintain endometrial lining
48
hCG
Human chorionic gonadotropic hormone
- Secreted by an implated embry
- Signals the corpus luteum to keep secreting progesterone
- (Progesterone maintains a thick endometrial lining)
49
Lipoprotein
- Transport lipids between intestines, liver, and other tissue
- Globular particules
- Core of triglycerides and cholesterol
- Surrounded by coat of protein, phospholipid, and cholesterol
50
5 Classes of lipoprotein
1. VLDL
2. IDL
3. LDL
(these 3 synth. in liver for lipid transport to other tissue)
4. HDL
5. Chylomicrons
51
Order of lipoprotein density
?????
?????
Chylomicrons
52
Apolipoprotein
Surround lipoproteins to hold them together
| Ex: apoB-100
53
Chylomicrons
- Are de-lipidated in capillaries
- Deliver dietary TG to tissue, deliver dietary cholesterol to liver
- Their TG's are hydrolyzed (lipoprotein lipase) and tissue takes up monoacylglycerol and FA
- They are now cholesterol-rich chylomicrons that re-enter circulation ---> liver
54
Carbamoyl phosphate synthetase
- Rate limiting step of Urea Cycle
- 2 ATP + HCO3 + NH3 ---> carbamoyl phosphate
- In liver mitochondria
- Enzyme is activated by N-acetylglutamate (made when there's an excess of glutamate due to protein breakdown)
55
Carniting palmitoyltransferase I
| CPT I
- Located in outer mitochondrial membrane, operates in intermembrane space
- FA-CoA ---> fatty acylcarnitine + CoA
56
The 3 ketone bodies
D(-)3-hydroxybutyrate
Oxloacetate
Acetone
57
All proucts released from full B-oxidation of Palmitate
- Palmitate = C16
- 8 rounds of B-ox (each round gives A-CoA + NADH + - FADH2)
- Each A-Coa goes through Krebs (GTP + 3 NADH + FADH2)
- In total, after Oxidative Phosphorylation ----> 106 AP
58
Acyl CoA Synthetase
FA + CoA + ATP ----> FA-CoA + AMP + PPi
- this is an activated FA
- FA-CoA can now enter the outer mitochondrial matrix
59
CPT-I
Carnitine palmitoyltransferase I
- sits in outer mitochondrial matrix
- FA-CoA + Carnitine -----> FA-carnitine + CoA
- FA-carnitine can now enter the mitochondrial matrix using CAT (carnitine acylcarnitine transferase)
60
CPT-II
Carnitine palmitoyltransferase II
- sits in inner mitochondrial matrix
- FA-carnitine + CoA -----> FA-CoA + Carnitine
- Now, FA-CoA can do B-oxidation in the matrix
- Now, Carnitine can go back to intermembrane space (here, carnitine in the shuttle for FA-CoA)
- Shuttle = CAT (carnitine acylcarnitine transferase)
61
```
CPT-I deficiency
And treatment (3)
```
- Only affects liver, liver can't use FA's
- Hypoglycemia
- Treated with
1. Avoid fasting
2. Lower LCFA in diet
3. Carnitine supplement
62
```
CPT-II deficiency
And treatment (3)
```
- Affects skeletal muscle (muscle weakness with exercise)
- Hyperammonemia (brown urine)
- Death
- Treated with
1. Avoid fasting
2. Lower LCFA in diet
3. Carnitine supplement
63
Carnitine
- Used to shuttle LCFA across inner mitochondrial membrane
| - SCFA and MCFA (2C - 12C) can diffuse on their own
64
HMG-CoA
- A-CoA, instead of going into Krebs, will go to HMG-CoA (ketogenesis) during starvation because there is no oxaloacetate for it to enter Krebs
- A-CoA ---> HMG-CoA ---> Ketone bodies (Acetone, Acetoac., 3-hydroxybutyrate)
65
Brown urine
Hyperammonemia
66
Ketone breath
- Hyperketonemia
- KB's are water soluble so they entre blood streat and make it into lung where they are exhaled
- Acetone has a slightly sweet smell
67
Arginino succinate synthetase
Urea cycle enzyme
- Allosteric inhibition my AMP
- Citrulline + ATP ---> Arginosuccinate
68
Carbamoyl phosphate synthetase-1
Urea cycle enzyme
- NH4+ + HCO3- + 2ATP ---> Carbamoyl-P
- Allosteric activation by N-acetylglutamate (made when there's an excess of glutamate due to protein breakdown)
69
Ornithine transcarbamoylase
Urea cycle enzyme
- Allosteric activation by citrulline
- Ornithine + carbamoyl-P ---> Citrulline (in mit. matrix)
70
Anticipation
Genetic disease gets worse with each generation
| Usually due to expansion of trinucleotide repeats
71
Epigenetic markers (3)
DNA Methylation - silencing (on C of CpG)
Histone Methylation - silencing
Histone Acetylation - expressing
72
Gonadal Mosaicism
WT parent has unobservable mutation in sex cells, can pass on this mutation to offspring
73
Anaphase lag
- Another way to get aneuploidy (other than nondisjunction)
| - One chr lags behind others during anaphase, left out of new nucleus
74
Non-chromosomal mosaicism
Due to error in mitosis early in development, error passed to all offspring
Can results in 2+ populations of cells in an individual
75
Chimera
Individual made of 2 genetically distinct cell populations arising from >1 zygote
Ex: Embryo fusion
76
Isochromosome
One arm is lost and the other is duplicated
| 2 p arms or 2 q arms
77
Robertsonian Translocation
- Between two acrocentric Chr (very small p arm)
| - Gives one large chr and one very small (usually degraded)
78
Uniparental Disomy
- Both in a pair of Chr come from single parent
79
Linkage disequilibrium
- SNP is in such physical proximity that it's always inherited with disease loci
80
RFLP
Restriction Fragment Length Polymorphism
- When cut by restriction endonucleases, different alleles can have different lengths
- Detectable with Southern Blot
- Example of Indirect Genetic Diagnosis
81
Hardy Weinberg Equilibrium
There is no change in allele or genotype freq. in a population over generations
Assumes
- Large pop
- Random mating
- No evolutionary forces (genetic drift, selection, ...)
82
STRP Analysis
- Indirect genetic analysis
| - Look for Short Tandem Repeat Polymorphisms of different lengths as markers for disease mutations
83
Amniocentesis
- Sample of amniotic fluid collected for genetic screening of embryo
84
Chorionic villus sampling
- Transabdominal/transcervical removal of chorionic villus sample
- Villi are of fetal origin
- Can do early in development, but higher risk to fetus (infection)
85
Kartagener Syndrome
"Primary ciliary dyskinesia"
- genetic
- dynein arms are missing/dysfunctions
- cilia/flagellum useless
- affects ALL systems that use ciliary transport
- high risk of ectopic pregnancy in females with syndrome
86
Capacitation
- Only capacitated sperm can penetrate zona pellucida
| - Uterus secretions shed sperm of glycoprotein coat and seminal proteins
87
Fimbrae
- Finger-like projections on ampula of Fallopian tubes
| - Work together with cilia on tube walls to beat and move egg down tube
88
4 things to look for in pegidree analysis
1. Any skipped generations? (skipped = recess, not = dom)
2. M/F equally affected? (No = X-linked)
3. M to M transmission? (Yes = NOT X-linked dom)
4. All offspring of affected F affected? (Yes = mitochondrial)
89
Heteroplasmy
Mitochondrial genomes may vary within a cell AND the proportion of each genome may be different cell to cell
90
Allelic Heterogeneity
Different mutations at same locus cause same phenotype
91
Locus Heterogeneity
A single disorder caused by mutations at different loci
92
Preeclampsia
Pregnancy-related high BP
Can be due to synctiotrophoblast cells not differentiating and not invading mothers arteries during trophoblast formation (~Days 10-12)
93
Synctiotrophoblasts
Part of the trophoblast
- secrete hCG when implanted
- secrete enzymes to break down endometrium ECM and invades endometrium
94
Depo-Provera
Depot-medroxyprogesterone acetate
- birth control
- progesterone analogue
- prevents ovulation
95
RU-486
Mifepristone
- Birth control
- Acts as anti-progesterone to prevent/reverse implantation
96
Placenta previa
- When the placenta covers the utero-vaginal opening
| - Due to ectopic pregnancy that plants near that bottom part of the uterus
97
Hydatidiform Mole
Mole = "false pregnancy"
- embryo fails to develop, trophoblast does develop
- complete mole = results from fertilization of empty oocyte
- partial mole = poorly developed embryo (usually triploid)
- secrete high levels of hCG
98
Persistent Trophoblastic Disease
- If a mole is not completely removed, it can become invasive
- ~5% of moles go on to form carcinomas
99
Rhogam
- To prevent hemolytic disease of the fetus (erythroblastosis fetalis)
- Given ~Week 28
- Rh- mom can attack Rh+ baby, especially if it's her second Rh+ baby
- Rhogam attacks Rh factors and mom is prevented from memory B-cell formation
100
Chorion frondosum
The "rough" fetal placenta
- the ticker part with villi
- connects to the umbillical cord
- the "smooth" side is the CHORION LAEVE
101
Decidua basalis
The maternal part of the placenta
| - "decidua" = it will shed with the placenta
102
Placenta Accretia
When embryonic placenta eats through to the uterus
- Accretia (75%) = eats through decidua basalis
- Incretia (15%) = eats through some myometrium
- Percretia (5%) = eats through entire myometrim/perimetrium
- These can all require hysterectomy at birth because placental/uterine tissue won't separate
103
Fetal circulation
Umbilical artery
- -> chorionic a
- -> fetal capillary in villus
- -> (exchange with maternal blood bath)
- -> chorionic v
- -> umbilical v
104
Oligohydramnios
| Causes and Complications
```
Too little amniotic fluid
Causes
- Renal agenesis
- amnion rupture
- chr abnormalities
Complications
- Lung hypoplasia
- Limb malformation
- Low growth
```
105
Polyhydramnios
| Causes and Complications
```
Too much amniotic fluid
Causes
- GI Obstruction
- Maternal diabetes
- Chr defecs
- High urine output by fetal kidneys
Complications
- High risk for placental abruption
```
106
Competence
| development
Actively aquiring the ability to espond to an inductive signal
must have two things:
1. signal receptor
2. the signaling pathway
107
```
Permissive interaction
(development)
```
All necessary genes are expressed but waiting for an environmental signal to proceed
108
Mesenchyme
- supporting cells
- loosely packed connective tissue
- mesodermal origin
109
Juxtacrine
- Non-diffusable signals
| - Go to adjacent cells
110
Sonic Hedgehog Pathway
```
Ligand: Hedgehog (cholesterol-activated)
Receptor: Patched
Action:
- Activated Smoothened
- Inhibits proteins from P-ing and U-ing Ci
- Ci is now a TF
```
111
Receptor Tyrosine Kinase Pathway
```
Paracrine
Ligand: FGF's and other Growth Factors
Receptor: Receptor Tyrosin Kinase
Action:
- Induce dimers that are activate kinases
- Sequence of phosphorylating
- Ras-MEK-ERK pathway ---> TF's
```
112
Smad pathway
Paracrine
Ligand: TGF-B family (ex: Nodal which does L-R axis)
Receptor: TGF-B Receptors( like Receptor Tyrosine Kinase)
Action: Receptors dimerize and P SMAD TF's
(This pathway involved in mesoderm formation)
113
JAK/STAT Pathway
```
Paracrine
Ligand: Prolactin
Receptor: JAK (Tyrosine Kinase Receptor)
Action: P STAT TF's which dimerize
(fetal bone growth
```
114
FGFR3
Fetal Growth Factor Receptor 3
- Uses JAK/STAT Pathway
- Signals chondrocytes to stop dividing and differentiate into cartilage
- Gain-of-function mutation results in dwarfism
115
Wnt Pathway
```
Paracrine
Ligand: Wnt
Receptor: Frizzled
Action:
- ligand binding inhibits Disheveled
- APC complex now active (usually disheveled inhibits it)
- This frees up B-catenin (a TF)
(APC Complex is a tumor suppressor, implicated in colon cancer)
```
116
Notch signaling
Juxtacrine
Ligand: Delta (transmembrane on inducing cell)
Receptor: Notch (transmembrane on responder cell)
Action:
- Cytoplasmic tail of Notch cleaved by proteases ---> TF
117
Integrins as receptors
- Transmembrane proteins
- Integrins bind ECM and IC actin
- Allows cell movement via actin contraction
- Involved in cell survival signaling
118
Connexins as receptors
- Found at gap junctions
- Create a small opening between cells for small soluble molecules to pass
- Can couple changes in ionic concentrations in two cells
119
Animal/Vegetal poles
- Dictated by polar body (polar body = animal pole)
120
Dorsal/Ventral poles
- Determined by location of Inner cell mass
- Near blastocyst = ventral
- Near edge = dorsal (contact with trophoblast)
