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Flashcards in Genetics, Biochem Deck (138)
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1

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

2

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

3

MPO deficiency

Can't produce H2O2

Neutrophils turn blue on nitro blue tetrazolium test

Normal NADPH activity: close to normal/normal immune system function

4

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)

5

Late complement component deficiency

Increased risk of Neisseria infection

6

Carbamoyl phosphate

1. de Novo pyramidine synthesis
2. Urea cycle
- Ornithine transcarbamoylase deficiency (OTC)--> accumulation of carbamoyl phosphate--> orotic acid

7

Hydroxyurea

Inhibits ribonucleotide reductase
- UDP can't be converted to dUDP (CTP buildup)

8

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

9

5-fluorouracil (5-FU)

Inhibits thymidylate synthase
--> can't produce dTMP

"F U thymidylate synthase"

10

Methotrexate (MTX)

Inhibits dihydrofolate reductase
---> can't produce dTMP

Supplement with Folinic acid (Leucovorin) to reverse methotrexate toxicity

11

Trimethoprim (TMP)

Inhibits BACTERIAL dihydrofolate reductase
--> can't produce dTMP

12

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

13

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

14

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

15

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

16

Missense mutation

Changed amino acid
- Conservative change: new amino acid is similar in chemical structure/function

17

Nonsense mutation

Early STOP codon (Stop the nonsense!)

18

Frameshift mutation

Changed from multiples of 3--> all nucleotides downstream misread
--> truncated, non-functional protein

19

Xeroderma pigmentosum

Nucleotide excision repair defect
- Can't repair thimine (pyramidine) dimers formed due to UV exposure (bulky adducts)

20

HNPCC

Hereditary nonpolyposis colorectal cancer
- Mutation in mismatch repair (unable to repair mismatched Watson-Crick nucleotides)

21

Ataxia telangiectasia

Mutation in nonhomologous end joining (bring together 2 ends of broken dsDNA)

22

Start codon

AUG
- Eukaryotes= methionine (may be removed before translation completed)
- Prokaryotes= formylmethionine

23

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

24

Amatoxins

Mushroom poison
Inhibits RNA polymerase II= halts mRNA synthesis--> cell death
- Found in Amanita phalloides= "death cap mushrooms)
- Severe hepatotoxicity if ingested

25

RNA polymerases

Eukaryotes:
- RNA Pol I= rRNA
- RNA pol II= mRNA (opens DNA at promoter site)
- RNA pol III= tRNA
** No proofreading function

Prokaryotes:
- RNA polymerase= multisubunit complex (all 3 RNA types)

26

snRNPs

Splice pre-mRNA
- Make lariat that is spliced out (intron), 2 exons joined

** Lupus= antibodies to spliceosomal snRNPs

27

I-cell disease

Inclusion cell disease
- Failure to add mannose-6-phosphate to lysosome proteins (needed to traffic protein from golgi to lysosome)
- Lysosome enzymes secreted outside cell instead of to lysosome

Symptoms:
- Coarse facial features
- Clouded corneas
- Restricted joint movement
- High plasma levels of lysosomal enzymes
- Fatal in childhood

28

Chediak-Higashi syndrome

Mutation in lysosomal trafficking regulator gene (LYST)
- Need LYST for microtubular sorting of endosomal proteins--> late multivesicular endosomes

Symptoms:
- Pyogenic infections (defective destruction of bacteria)
- Partial albinism (can't transport melanin)
- Peripheral neuropathy (can't transport proteins)

29

Kartagener's syndrome

Dynein (retrograde + --> - microtubule movement) arm defect in cilia

Symptoms:
- Male infertility (immotile sperm)
- decreased female fertility
- Bronchiectasis
- Recurrent sinusitis
** Associated with situs inversus (reversed organs)

30

Osteogenesis imperfecta

Type I collagen defect
- Type I collagen= Bone, skin, tendon, dentin, fascia, cornea, wound repair

Pathogenesis:
- Normal: Glycosylation of pro-alpha-chain hydroxylysine residues, formation of procollagen (H- and S-S bonds)--> triple helix
- OI= problem with formation of triple helix in Endoplasmic reticulum

Autosomal dominant (incomplete penetrance)

Symptoms:
- Multiple fractures with minimal trauma
- Blue sclerae (translucent connective tissue over choroidal vins)
- Hearing loss (abnL middle ear bones)
- Dental issues (lack of dentin= type I collagen)