Exam 2 Flashcards
Autosome
Chr1 - Chr22
Non sex Chromosome
Allosome
ChrX or ChrY
“Sex chromosome”
“gonosome”
Hemizygous
X-linked genes in males
Pleiotropy
When one gene affects multiple phenotypes Ex: The wolves turned dogs - Behavior - Floppy ears - Curly tails
Incomplete dominant trait
The heterozygote expresses an INTERMEDIATE phenotype
Ex: Flower color
- red x white = pink
Codominant
The heterozygote expresses BOTH phenotypes
ex: ABO blood typing
Haploinsufficiency
A single gene copy does NOT have the ability to express the WT phenotype
Dosage compensation
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
Barr body
Highly condensed Chr visible in nucleus during interphase
Expressivity
The severity of expression of the phenotype among individuals with the genotype
- Result of environmental factors (sex, exposure, …)
Penetrance
The probability that a gene will express a phenotype AT ALL
“Incomplete penetrance” = any penetrance under 100%
Early stage of embryogenesis
- 0 to 2 weeks
- starting with fertilization
- not sensitive to teratogens b/c not connected to mom yet
- right rate of lethality
Embryonic stage of embryogenesis
- 3 to 8 weeks
- period of greatest teratogen sensitivity
- organogenesis (all organs formed here)
- each organ system has its own period of peak sensitivity
Fetal stage of embryogenesis
- 9 to 38 weeks
- decreasing teratogen sensitivity
- period of functional maturation
Teratogen
anything that causes birth defects
Congenital
Present at birth
Malformation
- The tissue itself is flawed
- Etiology: genetic, teratogenic —- morphogenic error
- ex: spina bifida, myelomeningocele
Deformation
- Due to extrinsic factor
- Etiology: Extrinsic (fetal constraint), intrinsic (fetal akinesia) —> abnormla force
- ex: club foot
Disruption
- Normal development stops
- Etiology: vascular, compressive, tearing —> vasculor occlusion (any abnormal force)
Trisomy 21
Downs Syndrome
- Extra copy of chr21
- Growth/mental retardation
- Craniofacial defects: brachycephaly, small nose, …
- Cardiac defects: in 40%, septal defects of PDA
Trisomy 18
“18 year olds want to fight”
Edward Syndrome
- Mental retardation
- Clenched fists: flexion of fingers/hands
Trisomy 13
“13 in unlucky, people spit like puh-tooy for luck”
Patau Syndrome
- Mental retardation
- Deafness
Trisomy 8
“the 8 is long in the trunk”
Warkany Syndrome
- Mental retardation
- Long, slender trunk
47, XXY
Klinefelter Syndrome
- Male
- Presence of Barr bodies
- Sterile, testicular atrophy
- Gynechomastia
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
47, XXX
Triple X Syndrome
- Female
- 2 Barr bodies
- Amenorrheic
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
Deletion 4q syndrome
Partial deletion of 4q (long arm)
- Cleft lip
- Limb abnormalities
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
Prader-Willi Syndrome
Microdeletion on 15q (on paternal chr)
- Obesity
- Hypotonia
- Hypogonadism
Miller-Dieker Syndrome
Microdeletion on 17p
- Lissencephaly (smooth brain)
- Microcephaly
- Sever mental retardation
Maternal imprimting
Means that mom’s genes are silenced
Epigenetic
Primordial Germ Cells
Arise from epiblast (Week 2)
Give rise to all gametes
Monosomy
Diploid individual who has only 1 copy of a chr
Trisomy
Diploid individual who has 3 copies of a chr
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
Sertoli cells
Supporter cells of primordial germ cells in males
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)
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
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
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)
Zona pellucida
- Layer between maturing oocyte and granulose cells
- Full of glycoprotein (secreted by both oocyte and follicle cells)
Antrum
- Empty space found in the maturing follicle
Cumulus oophorus
- The granulosa cells that exit the ovary along with the secondary oocyte during ovulation
Menstrual phase
- If fertilization does not occur, endometrial lining sloughs off
(requires progesterone)
Proliferative/Follicular phase
- As follicle develops in ovary
- Granulosa cells produce estrogen
- Causes endometrial lining to thicken
Secretory/Progestational Phase
- After ovulation
- Corput luteum produces progesterone to maintain endometrial lining
hCG
Human chorionic gonadotropic hormone
- Secreted by an implated embry
- Signals the corpus luteum to keep secreting progesterone
- (Progesterone maintains a thick endometrial lining)
Lipoprotein
- Transport lipids between intestines, liver, and other tissue
- Globular particules
- Core of triglycerides and cholesterol
- Surrounded by coat of protein, phospholipid, and cholesterol
5 Classes of lipoprotein
- VLDL
- IDL
- LDL
(these 3 synth. in liver for lipid transport to other tissue) - HDL
- Chylomicrons
Order of lipoprotein density
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Chylomicrons
Apolipoprotein
Surround lipoproteins to hold them together
Ex: apoB-100
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
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)
Carniting palmitoyltransferase I
CPT I
- Located in outer mitochondrial membrane, operates in intermembrane space
- FA-CoA —> fatty acylcarnitine + CoA
The 3 ketone bodies
D(-)3-hydroxybutyrate
Oxloacetate
Acetone
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
Acyl CoA Synthetase
FA + CoA + ATP —-> FA-CoA + AMP + PPi
- this is an activated FA
- FA-CoA can now enter the outer mitochondrial matrix
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)
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)
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
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
Carnitine
- Used to shuttle LCFA across inner mitochondrial membrane
- SCFA and MCFA (2C - 12C) can diffuse on their own
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)
Brown urine
Hyperammonemia
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
Arginino succinate synthetase
Urea cycle enzyme
- Allosteric inhibition my AMP
- Citrulline + ATP —> Arginosuccinate
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)
Ornithine transcarbamoylase
Urea cycle enzyme
- Allosteric activation by citrulline
- Ornithine + carbamoyl-P —> Citrulline (in mit. matrix)
Anticipation
Genetic disease gets worse with each generation
Usually due to expansion of trinucleotide repeats
Epigenetic markers (3)
DNA Methylation - silencing (on C of CpG)
Histone Methylation - silencing
Histone Acetylation - expressing
Gonadal Mosaicism
WT parent has unobservable mutation in sex cells, can pass on this mutation to offspring
Anaphase lag
- Another way to get aneuploidy (other than nondisjunction)
- One chr lags behind others during anaphase, left out of new nucleus
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
Chimera
Individual made of 2 genetically distinct cell populations arising from >1 zygote
Ex: Embryo fusion
Isochromosome
One arm is lost and the other is duplicated
2 p arms or 2 q arms
Robertsonian Translocation
- Between two acrocentric Chr (very small p arm)
- Gives one large chr and one very small (usually degraded)
Uniparental Disomy
- Both in a pair of Chr come from single parent
Linkage disequilibrium
- SNP is in such physical proximity that it’s always inherited with disease loci
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
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, …)
STRP Analysis
- Indirect genetic analysis
- Look for Short Tandem Repeat Polymorphisms of different lengths as markers for disease mutations
Amniocentesis
- Sample of amniotic fluid collected for genetic screening of embryo
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)
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
Capacitation
- Only capacitated sperm can penetrate zona pellucida
- Uterus secretions shed sperm of glycoprotein coat and seminal proteins
Fimbrae
- Finger-like projections on ampula of Fallopian tubes
- Work together with cilia on tube walls to beat and move egg down tube
4 things to look for in pegidree analysis
- Any skipped generations? (skipped = recess, not = dom)
- M/F equally affected? (No = X-linked)
- M to M transmission? (Yes = NOT X-linked dom)
- All offspring of affected F affected? (Yes = mitochondrial)
Heteroplasmy
Mitochondrial genomes may vary within a cell AND the proportion of each genome may be different cell to cell
Allelic Heterogeneity
Different mutations at same locus cause same phenotype
Locus Heterogeneity
A single disorder caused by mutations at different loci
Preeclampsia
Pregnancy-related high BP
Can be due to synctiotrophoblast cells not differentiating and not invading mothers arteries during trophoblast formation (~Days 10-12)
Synctiotrophoblasts
Part of the trophoblast
- secrete hCG when implanted
- secrete enzymes to break down endometrium ECM and invades endometrium
Depo-Provera
Depot-medroxyprogesterone acetate
- birth control
- progesterone analogue
- prevents ovulation
RU-486
Mifepristone
- Birth control
- Acts as anti-progesterone to prevent/reverse implantation
Placenta previa
- When the placenta covers the utero-vaginal opening
- Due to ectopic pregnancy that plants near that bottom part of the uterus
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
Persistent Trophoblastic Disease
- If a mole is not completely removed, it can become invasive
- ~5% of moles go on to form carcinomas
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
Chorion frondosum
The “rough” fetal placenta
- the ticker part with villi
- connects to the umbillical cord
- the “smooth” side is the CHORION LAEVE
Decidua basalis
The maternal part of the placenta
- “decidua” = it will shed with the placenta
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
Fetal circulation
Umbilical artery
- -> chorionic a
- -> fetal capillary in villus
- -> (exchange with maternal blood bath)
- -> chorionic v
- -> umbilical v
Oligohydramnios
Causes and Complications
Too little amniotic fluid Causes - Renal agenesis - amnion rupture - chr abnormalities Complications - Lung hypoplasia - Limb malformation - Low growth
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
Competence
development
Actively aquiring the ability to espond to an inductive signal
must have two things:
1. signal receptor
2. the signaling pathway
Permissive interaction (development)
All necessary genes are expressed but waiting for an environmental signal to proceed
Mesenchyme
- supporting cells
- loosely packed connective tissue
- mesodermal origin
Juxtacrine
- Non-diffusable signals
- Go to adjacent cells
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
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
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)
JAK/STAT Pathway
Paracrine Ligand: Prolactin Receptor: JAK (Tyrosine Kinase Receptor) Action: P STAT TF's which dimerize (fetal bone growth
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
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)
Notch signaling
Juxtacrine
Ligand: Delta (transmembrane on inducing cell)
Receptor: Notch (transmembrane on responder cell)
Action:
- Cytoplasmic tail of Notch cleaved by proteases —> TF
Integrins as receptors
- Transmembrane proteins
- Integrins bind ECM and IC actin
- Allows cell movement via actin contraction
- Involved in cell survival signaling
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
Animal/Vegetal poles
- Dictated by polar body (polar body = animal pole)
Dorsal/Ventral poles
- Determined by location of Inner cell mass
- Near blastocyst = ventral
- Near edge = dorsal (contact with trophoblast)
