Gen Flashcards
Promoter
Ex: Tata box
Chargoff’s Rules
Relate amounts of bases
dA=dT and dC=dG
Splice donor
GU (1st) 5’
Splice acceptor
AG (2nd) 3’
Lariat
intron spliced out (“A” branch point)
- RNA Pol I
- RNA Pol II
- RNA Pol III
- rRNA
- mRNA
- tRNA
Enhancer
Can be far ways. Increase the activation of the Pol. Increasing basal level of transcription
Cis regulatory element
DNA binding site (on DNA itself)
- Basal Promoter sequence (TATA BOX)
- Proximal control regions
- Enhancer sequence
Trans regulatory element
proteins that bind to CIS regulatory elements
- Ex: Transcription factors
Activators
Bind to it Enhancers
Regulatory sequence
regulates the rates at which transcription of the gene occurs
Extragenic DNA
- juck DNA (less than 2% of DNA coding DNA)
- role in regulation
Tandem Repeats
Setellite, Minisatellite (telomeric, Hypervariable), Microsatellite
(VNTR and STR)
Insterspersed
SINE and LINE (50% of genes)
Area of gene density
Subtelomeric region
VNTR and STR
- Tandem repeats, inherited in co-dominent
- fingerprinting
SINE
- <500bp
- 10%
- Alu
LINE
- 6000bp
- have reverse transcriptase (Transposable elements)
Pseudogenes
genes that are not expressed
P arm
q arm
- short arm
- long arm
Metacentric Chromosome
Centromere in center
- Chrom 1
Submetacentric Chromosome
Centromere off to one side
- Chrom 4
Acrocentric Chromosome
Centromere near the end
- Chrom 13, 14,15,21,22
Uniparental disomy
Both pairs of Chromosomes from one parent
X- inactivation gene
XIST gene (Xic) - not entirely inactive
Imprinting
- gene being methylated (inactive)
Huntingtion’s Gene
- Chromosome 4p
Labile Cells
Multiply throughout life (epitheial cells)
Stable Cells
Go phase, can divide if appropriately stimulated
Permanent Cells
Permanently in Go phase
Quenching
Repressor binds to the DNA-binding domain
Blocking
Repressor binds to the Activation domain
Response element
a short sequences of DNA within a gene promoter region that are able to bind a specific transcription factor and regulate transcription of genes
Dicer enzyme
turns double stranded RNA to ssRNA
Charcot-Marie Tooth
- Autosomal Dominant
- Locus Heterogeneity
Familial Hypercholesterolemia (LDL receptor deficiency)
-Autosomal Dominant
Huntington Disease
- Autosomal Dominant
- Tripple repeat expansion (CAG) [50 late onset, 100 early onset]
- Late onset (age-dependent penetrance
- Gain-of-function
Myotonic dystophy
- Autosomal Dominant
- Tripple repeat expansion (CTG)
- DMPK gene*
- Wasting of muscle, cataracts, heart conduction defect,endocrine changes, and myotonia
Marfan syndrome
- Autosomal Dominant
- Pleiotropy
- HOT SPOT
Osteogenesis Imperfecta
- Autosomal Dominant
- Dominant-negative
- Variable expression
- Pleiotropy
- Locus Heterogeneity (Chro 17 {COL1A1} Chro 7{COL1A2})*
- HOT SPOT
Achondroplasia
- Autosomal Dominant
- FGFDR3 gene*
- homo, not compatible with life (2/3)
- Gain of function
- HOT SPOT (FGFR3) (80% new mutations)
Neurofibromatosis Type 1
- Autosomal Dominant
- NF-1 gene*
- Allelic heterogeneity (compound hertrozygous)
- Variable expressivity
- cafè- au-lait spots, neurofibromas, litchi nodules in eyes
- HOT SPOT (NF1)
Acute intermittent porphyria
- Autosomal Dominant
Sickle Cell Anemia
- Autosomal recessive
- pseudo-autosomal dominant
Cystic fibrosis
- Autosomal recessive
- Allelic Heterogeneity (most common (delta F508)), N1303K
Phenylketonuria (PKU)
- Autosomal recessive
Tay-Sachs disease
- Autosomal recessive
Congenital desafness
- Autosomal recessive
Hemochromatosis
- Autosomal recessive
- Delayed age of onset
- Allelic heterogeneity
- H63D, S65C, C282Y*,
Alkaptonuria
- Autosomal recessive
- Delayed age of onset
Homocystinuria
- Autosomal recessive
- Variable expression
Galactosemia
- Autosomal recessive
SCID
- Autosomal recessive
- ADA deficiency
- Locus Heterogeneity
MOST ENZYME DIFICIENCEIS
- Autosomal recessive
Dystophin disorders
- X-linked Recessive
- HOT SPORT (Dysrophin gene)
Glucose-6-phosphate dehydrogenase (G6PD)
- X-linked Recessive
Hemophilia A and B
- X-linked Recessive
- low clotting factor 8
- Allelic heterogeneity
Lesch-Nyhan Syndrome
- X-linked Recessive
- HGPRT*
Red-green color blindness
- X-linked Recessive
X-linked SCID
- X-linked Recessive
- SCIDX1* (gamma chain)
- Locus Heterogenasis
Rett Syndrome
- X-linked Dominant
Incontinentia Pigmenti
- X-linked Dominant
Vitamin D resistant Rickters
- X-linked Dominant
Fragile X
- X-linked Dominant
- Triple repeat (CGG) [on FMR1 gene]
Various mutations in the SRY genes
- Y-linked
H-Y histocompatibility antigen
- Y-linked
Hairy ears
- Y-linked
Xerdoerma pigmentosum
- autosomal recessive
- Variable expression
Optic neuropathy
-Mitochondrial
MELAS
-Mitochondrial
MERRF
-Mitochondrial
Digenic disorders
- Retinitis Pigmentosa
- necessary to have both mutations for the disorder (ROM1 and peripherin)
Imprinting
- Methylate to science gene
- Prader Willie Syndrome(no father loci) (NO SNRPN [15q11-13])*
- Angelman Syndrome (no mother loci) (NO UBE3A [15q11-13])
Triple repeat disorders
- (anticipation) constent repeating of the same three nucleotides the higher the great chance of getting the disorder
- Friedrich ataxia
4 alpha and 2 beta globin genes are on what chrome.
- chromosomes 16(alpha) and 11 (beta)
Hemoglobinopathies
- Qualitatitive change, Mutation in nucleotide sequence of globin chain
Thalassemia
- QuaNtitative change (number): Decreased or absent globin chain synthesis
5-azacytidine and Decitabine
- Demethylating agent
Hydroxyurea
- Most commonly used to treat sickle cell anemia
Butyrate compounds
- Inhibit histone deacetylation
Sickle Cell Trait
- Carrier of sickle cell
a-Thalassemia cause…
- Unequal crossing over during homologous recombination
Hemoglobin H (HbH) disease
- α-thalassemia, 3 deletions
- hair on end
Hb Bart
- Dye at birth, all 4 alpha globins deleted
Malformations
- Genetics and environments ( abnormality at initial formation of organ)
- Single Abnormalities
Disruptions
- Disturbances after an organ has been formed
- Environment (shortened arms or legs resulting form vascular problem)
- Single Abnormalities
Deformations
- Mechanical distortions, (clubfoot)
- Single Abnormalities
Dysplasias
- Abnormalities in tissue organization
- Single Abnormalities
Sequences
- Cascades of effects
- Multiple Abnormalities
Syndromes
- Multiple Abnormalities
- Groups of anomalies, due to single underlying cause
Associations
- Where traits coincide more often than expected
- Multiple Abnormalities
SHH (Sonic Hedge hog)
- Chromosome 7 (7q36)
- Regulates gene formation
IF SHH mutated
- Holoprosenchephaly (HPE3) [savorily varieis]
- Polydactyly [postulated]
Hypertelorism (double face)
- over expression of SHH
Polydactyly
- Over expression of SHH or mutation in Gli3
- disruption of Hoxd13 gene
Holoprosencephaly
- mutation in SHH or Six3 gene (regulator of SHH)
Smith- Lemi- Opitz Syndrome
- mutation in 7-dehydroholestrol reductase
Gorlin Syndrome (Nevoid basal cell carcinoma)
- Mutation in Patched (PTCH)
- Rib defects
Pallister- Hall Syndrome
- Mutation in Gli
- brain tumors, polydactyl
Rubinstein-Taybi Syndrome
- Mutation in the CREBBP gene
- broad thumbs and toes, short stature, small head, facial features
HOX gene
- Dont change between species
- Transcription factors
- Segmentation ( confer identity to individual body segments
Cancer and cervical ribs
- mutation in HOX??
- Higher frequency of cancer than general population
De La Chapelle Syndrome
- recombination of SRY gene ( XX male)
- infertility, 10% show hypospadias
Pure Gonadal Dysgenesis
- XY female, loss of function of SRY GENE
Pharmacokinetic Variation
- Variation in proteins involved in drug metabolism or transport
- Enzymes that catalyze drug metabolism
Pharmacodynamic Variation
- Variation in drug targets
potency
Butyrlcholinesterase (BChE)
- Breaks down Succinylcholine (fast)
- Defect in BChE is AUTOSOMAL RECESSIVE*
- Normal # above 75
under 20 (homo)
N-acetlytransferase 2 (NAT2)
- Breaks down Isoniazid (Acetylation way of metabolization)
- Autosomal recessive
- lower then 3 in plasma concentration
CYP2D6
- Breaks down antidepressants, antiarhythmics, analgesics
- Debisoquine(antihypertensive) and sperteine (oxytotic)
- Autosomal recessive
- Breaks down: metoprolol, haloperidol, codeine, dextromethorphan, fluoxetine, imipromine, desipromine
Thiopurine S-Methyltransferase (TPMT)
- break down method is S-methylation
- 6-mercaptopurine and azathioprine
CYP2C9
- Warfarin Breakdown
Idiosyncratic
- result from interactions between the drug and a unique aspect of the physiology of the individual patient
G6PD
- protects RBC from oxidative injury (NADPH)
Malignant Hyperthermia
- fatal genetic disorder of skeletal muscle
- Autosomal dominant
- main couse of death due to anesthesia
- altered control of Ca++ release
- Ryanodine receptor gene (RYR1)
- Caffeine-Halothane Muscle Contracture Test
- Halothane Test
- Caffeine Test
- tests for Malignant Hyperthermia
Quantitative trate
- Number of dominance alleles determine phenotype
liability
- All factors that contribute to a disease
- Genetic is hight
Threshold
- At a certion point in which you will get the illness
Concordance
- both twins have the same disorder
- if 100% disorder is genetically determined
Discordance
- one twin has the disorder and the other does not
