Genetics, Biochem Flashcards
Turner’s syndrome
Missing X (XO phenotype)
- -> lose ovarian follicles after birth “streak ovaries”
- -> increased LH, FSH
Symptoms:
- Short, shield chest, webbed neck
- Lymphedema: cystic hygroma (posterior triangle of neck) at birth–> lymph outflow problems
- CV malformations= coarctation of aorta, bicuspid aortic valve, aortic dissection
- Horseshoe kidney
- Dysgerminoma
- most common cause of primary amenorrhea
Leukocyte adhesion syndrome
Genetic CD18 deficiency–> no integrin formation–> leukocytes can’t migrate from vasculature
Symptoms:
- No pus formation
- Late separation of umbilicus
- Poor wound healing
Labs:
- Neutrophilia
MPO deficiency
Can’t produce H2O2
Neutrophils turn blue on nitro blue tetrazolium test
Normal NADPH activity: close to normal/normal immune system function
Chronic granulomatous disease
No NADPH oxidase
- No respiratory burst in neutrophils
Symptoms:
- Susceptible to catalase-positive infections (can break down H2O2 produced by MPO)= S. aureus, E. coli, aspergillus
Labs:
- Neutrophils don’t turn blue on nitro blue tetrazolium test
- Abnormal dihyrorhodamine (DHR) flow cytometry test)
Late complement component deficiency
Increased risk of Neisseria infection
Carbamoyl phosphate
- de Novo pyramidine synthesis
- Urea cycle
- Ornithine transcarbamoylase deficiency (OTC)–> accumulation of carbamoyl phosphate–> orotic acid
Hydroxyurea
Inhibits ribonucleotide reductase
- UDP can’t be converted to dUDP (CTP buildup)
6-mercaptopurine (6-MP)
Blocks PRPP amidotransferase–> blocks de novo purine synthesis
- Azathioprine–> 6-MP
- de novo purine synthesis requires Glycine, Aspartate, Glutamine (GAG) and THF (tetrahydrofolate)
- PRPP amidotransferase also inhibited by AMP, GMP, IMP, allopurinol
5-fluorouracil (5-FU)
Inhibits thymidylate synthase
–> can’t produce dTMP
“F U thymidylate synthase”
Methotrexate (MTX)
Inhibits dihydrofolate reductase
—> can’t produce dTMP
Supplement with Folinic acid (Leucovorin) to reverse methotrexate toxicity
Trimethoprim (TMP)
Inhibits BACTERIAL dihydrofolate reductase
–> can’t produce dTMP
Orotic aciduria
UMP synthase defect (autosomal recessive)
- Can’t convert orotic acid to UMP
Symptoms:
- Orotic acid in urine (NO hyperammonemia)
- Megaloblastic anemia (can’t help with B12 or folic acid)
- Failure to thrive
Tx:
- Oral uridine monophosphate administration
OTC deficiency
Ornithine transcarbamoylase deficiency (OTC)–> accumulation of carbamoyl phosphate–> orotic acid
Symptoms:
- Orotic acid in urine
- Megaloblastic anemia (can’t help with B12 or folic acid)
- Failure to thrive
- Hyperammonemia
Adenosine deaminase deficiency
- -> buildup of excess ATP, dATP–> feedback inhibition of ribonucleotide reductase–> inhibition of DNA synthesis
- -> decreased lymphocyte count (high turnover cells)–> SCID
Autosomal recessive
Lesch-Nyhan syndrome
Absence of HGPRT
- Normally converts hypoxanthine to IMP, guanine to GMP
–> excess uric acid, de novo purine synthesis
X-linked recessive
- Retardation, self-mutilation, aggression, hyperuricemia, gout, choreoathetosis
Missense mutation
Changed amino acid
- Conservative change: new amino acid is similar in chemical structure/function
Nonsense mutation
Early STOP codon (Stop the nonsense!)
Frameshift mutation
Changed from multiples of 3–> all nucleotides downstream misread
–> truncated, non-functional protein
Xeroderma pigmentosum
Nucleotide excision repair defect
- Can’t repair thimine (pyramidine) dimers formed due to UV exposure (bulky adducts)
HNPCC
Hereditary nonpolyposis colorectal cancer
- Mutation in mismatch repair (unable to repair mismatched Watson-Crick nucleotides)
Ataxia telangiectasia
Mutation in nonhomologous end joining (bring together 2 ends of broken dsDNA)
Start codon
AUG
- Eukaryotes= methionine (may be removed before translation completed)
- Prokaryotes= formylmethionine
Stop codons
UGA (U Go Away)
UAA (U Are Away)
UAG (U Are Gone)
** Does not code for Amino Acid–> stop codon causes Releasing Factor (RF) to bind to ribosome
Amatoxins
Mushroom poison
Inhibits RNA polymerase II= halts mRNA synthesis–> cell death
- Found in Amanita phalloides= “death cap mushrooms)
- Severe hepatotoxicity if ingested