Klein-waardenburg syndrome is due to mutation in the PAX gene which is responsible for the right time of fetal development Symptoms:- Limb abnormality Defense Pigmentary abnormality Distopia cnthorum (lateral displacement of the eye inner corner)

Purines are adenine and guanine

Thymine dimers damage caused by UV leads to XP if we have a missing excision endonuclease "G1"

RNA types rRNA most abundant tRNA carry amino acid to the riposom mRNA carry info of sequence (translated) hnRNA eukaryote , RNA precursor snRNA eukaryote , remove introns

Start codon (AUG) Stop(nonsense) codons (UAA,UGA,UAG)

Protein synthesis begins with methionine (met) in eukaryote Begin with formylmethionine (fmet) in prokaryotes

All amino acid have more than one codon except Met and Trp

In sickle cell anemia we have missense mutation Glu->Val Glutamate->valen Vasoclosive crisis and hemolysis can actually happen because of it

Mutations Silent mutation, missense mutation (sickle-cell) Nonsense mutation, (stop) frameshift mutation,( 1-2piece deletion or addition )

Mutations Large segment deletion-> α thalesmia Splice site - β thalesmia Triplet repeat expansion -> Huntington disease , miotonic dystrophy ,fragile x ,friedrech ataxia

Huntington disease : autosomal dominant mean age 43 to 48 symptoms : hyperreflexia 1st, mood disturbance ,memory\/ , abnormal gait, dysphagia , dementia

In proteins the peptide bond is between the carboxyl group and The amino group

Prokaryotic translation inhibitors are Striptomycin , Erythromycin , tetracycline ,chloramphenicol

Eukaryotic translation inhibitors cycloheximide , diphtheria toxins ,pseudomonas toxins

Grey baby syndrome symptoms : blue lips nailbeds and skin (cyanosis )death, Low blood pressure Trigger :chloramphenicol (antibiotic against meningitis)

DNA replication Unwinding :helicase Stabilization :SSB Synthesis of RNA Primers :primase Synthesis of DNA : polymrase ||| (prokaryotes) polymrase α , δ (Eukaryote)

Removal of RNA (Prokaryotes DNA POLYMRASE 1)(eukaryotes RNAase H) Replacement of RNA (Prokaryotes DNA POLYMRASE 1)(eukaryotes ) Joining of OkaZaki fragments ligase

Rnap1:rRNA (nucleolus) except 5s RNAP2:(nucleoplasm)hnRNA/mRNA some snRNA RNAP3:(nucleoplasm)tRNA,5S rRNA TFIID bind before RNA polymerase RNAP2 inhibited by α-amanitin(mushrooms)

Prokaryotes RNA α2ββ polymerase Requires sigma σ to initiate a promoter Requires rho ρ to terminate (sometime) Inhibited by rifampin and actinomycin D

Ubiquitin helps proteasomes

|-cell disease happens due to genetic defect in the phosphorylation of the protein oligosaccharide chain Symptoms- Gingival hyperplasia Scoliosis Lysosomes in blood Mitral valve defect

Collagen 1 - bone skin tendons (osteogenesis imperfecta+Enhler-danlos) 2-cartilage vitreous humor 3-vessels granulation tissue (enhler-danlos4+keloid formation) 4-basement membrane (good paasture+aplort+epidermolysis bullosa)

Scurvy Deficient hydroxylation secondary to ascorbate(c) deficiency Symptoms Loose teeth Bleed gum Poor wound healing Poor bone development

Osteogenesis imperfecta Due to mutation in collagen type 1 genes Symptoms Skeletal deformities fractures Blue Sclera

Ehlers-danlos syndrome Due to a defect in the 1 and 3 collagen genes Symptoms Hyper extensible fragile skin hypermobile joints Dislocation Varicose veins ecchymoses arterial and intestinal ruptures

Fibrates and thiazolidinediones(DM2) are used to do lower serum TGs

Fibrates activate PPARα Thiazolidinediones activate PPARγ PPARs R transcription factors ,thy bind to PPRES and regulate lipid metabolism PP stands for peroxisome proliferator (Zinc finger)

NFKB (nuclear factor kappa-b)is a specific transcription factor that binds to KB elements in the DNA to initiate inflammatory response It's inhibited by glucocorticoid Glucocorticoid \/ signaling

Zellweger syndrome a genetic disease caused by mutation in genes involved in peroxisome biogenesis which lead to fat accumulation Symptoms:- Enlarged liver high levels of Cu and Fe vision problems, failure to grow retardation,die within a year

Thalidomide is morning sickness treatment used for pregnant woman In th 60s it prevent the binding of the homeodomain protein to the enhancer portion which lead to limp abnormality

Focomelia is limb abnormality caused by thalidomide

Ζn finger protein All steroid hormones ( estrogen cortisol..) Thyroid hormone (lipid) Vitamin A,D

Glucagon is peptide hormone doesn't go inside the cell , its activate cAMB which activate CREB(cAMB response element binding)protein

In Cushing syndrome we have ^cortisol which lead to hyperglycemia which lead to^insulin which lead to hyperlipidemia

Blood -cells=plasma Plasma - clotting factor = serum

Osmolality =300

Major fluid loss treatment is isotonic saline "normal saline"

Hypertonic solutions infusion will cause seizures , CNS abnormalities ~>death

Loss of isotonic fluid due to hemorrhage,diarrhea,vomiting will lead to only ECF Volume decreasing

Loss of hypotonic fluid due to dehydration, diabetes insipidus , alcoholism will lead to ECF volume decreases Osmolality increase ICF volume decrease

Gaining isotonic fluid increases ECF volume only

Gaining of hypotonic saline or water intoxication will lead to ECF volume ^ Osmolality \/ ICF volume ^

Gaining of hyper tonic fluid(mannitol) will lead to ECF volume ^ Osmolality ^ ICF volume \/

Only arteriole control the blood flow "thy constrict"

Starling equation Qf=k[(Pc+DELTAif)-(Pif+DELTAc)] Delta=oncotic pressure P= hydrostatic pressure

Edema causes Pc^ -blood flow^e.g.,vasodilation Venues pressure ^e.g.,venous obstruction or heart failure Blood volume ^(Na retention)e.g.,heart failure

Edema causes 2 Oncotic if ^ due to thyroid disfunction (non pitting) Oncotic c \/ :- -liver failure -nephrotic syndrome

Edema causes 3 Increased capillary permeability (k) Circulating agents :- TNF alpha,bradykinin ,histamine burn.. Fluid ^

Pulmonary edema Cardiogenic due to ^left arterial pressure always have elevated wedge pressure treated with diuretic Non cardiogenic due to injury to alveolar epithelium or to capillaries causes are sepsis or aspiration pneumonia wedge pressure is low or normal