Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

First Aid > Biochemistry > Flashcards

Biochemistry Flashcards

1
Q

Chromatin structure

A

DNA exists in condensed chromatin form in order to fit into nucleus.

  • DNA wraps around histones to make nucleosome
  • Histones are rich in lysine and arginine
  • H1 binds to nucleosome and to linker DNA
  • In mitosis: DNA condenses to form chromosomes.
  • DNA and histone synthesis occur during S phase
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Heterochromatin

A

Condense, transcriptionally inactive, sterically inaccessible

(HighlyCondensed)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Euchromatin

A

Less condensed, transcriptionally active

Eu= truely “transcribed”

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

DNA methylation

A

Template strand are methylated in DNA replication

  • allows mismatch repair enzymes to distinguish between old and new strands
  • Methylation at CpG islands represses transcription
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Histone Methylation

A

Reversibly represses DNA transcription, but can activate it in some cases

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Histone acteylation

A

Relaxes DNA coiling, allowing for transcription

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Purine

A

A, G

  • Start with sugar + phosphate (PRPP)
  • add base
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Pyrimidines

A

C,U,T

  • Thymine has a methyl
  • Uracil in RNA, Thymine in DNA

Synthesis

  • Make Orotic acid
  • add sugar & phosphate (PRPP)
  • modify base
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Leflunomide

A

inhibits dihydroorotate dehydrogenase

(carbamoyl phosphate—> Orotic acid)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Mycophenolate

Ribavirin

A

Inhibit IMP dehydrogenase

(IMP–> GMP)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Hydroxyurea

A

inhibits ribonuclotide reductase

  • UDP–> dUDP
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

6 Mercaptopurine (6MP)

Azathioprine (pro-drug)

A

inhibits de novo purine synthesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

5 Flurouracil (5FU)

A

Inhibits thymidylate synthase

dUMP–> dTMP

decreases deoxythymidine monophosphate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Methotrexate (MTX)

Trimethoprim (TMP)

Pyrimethamine

A

Inhibits dihydrofolate reductase

THF–> DHF

  • DHF required in dUMP–> dTMP
  • leads to decreased dTMP in humans, bacteria and protozoa
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Adenosine deaminase deficiency

A

Excess ATP and dATP imbalances nucleotide pool via feedack inhibition of ribonuclotide reductase

  • Prevents DNA synthesis and thus decrease lymphocyte count
  • one of themajor causes of autosomal recessive SCID
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Lesch-Nyhan Syndrome

A

Defective purine salage due to absent HGPRT

  • converts Hypoxanthine to IMP & guanine to GMP
  • results in excess uric acid production
  • x-linked recessive
  • Tx: allopurinol or febuxostat

HGPRT

  • Hyperuricemia
  • Gout
  • Pissed off (aggressive)
  • Retardation (intellectual disability)
  • DysTonia
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

DNA replication

A
  • Origin of replication
  • Replication fork: where leading and lagging strands are synthesized
  • Helicase: unwinds DNA
  • Single stranded binding proteines: prevents strands from re- annealing
  • DNA topoisomerases: creates a single or souble stranded break in helix to add or remove supercoils ( inhibited by fluoroquinolone)
  • Primase: makes an RNA primer on which DNA polymerase can initiate replication
  • DNA pol III: prokaryotic only ( elongation). Has a 3’–> 5’ exonuclease for proofreading
  • DNA pol I: prokaryotic only: decreases RNA primer & replaces it with DNA
  • DNA ligase: catalyzes the formation of phosphodiester bond within a second strand of dsDNA
  • Telomerase: RNA dependent DNA pol that adds DNA to 3’ end to avoid loss of genetic material
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Mutations in DNA

A

Transition: Purine to purine

Transversion: purine to pyrimidine

  • Silent: substitution codes for some amino acid
  • Missense: substitution results in changed amino acid
  • Nonsense: substitution results in early stop codon
  • Frameship: deletion or insertion of a number of nucleotides not divisible by 3 ( results in truncated, nonfunctional protein)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Nucleotide excision repair

A

specific endonucleases release the oligonucleotide containing damaged base

  • DNA polymerase and ligase fill and reseal the gap
  • repairs bulk helix distorting lesion
  • Defective in xeroderma pigmentosum which prevents repair of pyrimidine dimers because of UV light exposure
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Base Excision Repair

A

Base specific glycosylase recognize altered base and creates AP site (apurinic/apyrimidinic)

  • One or more nucleotides are removed by AP endonuclease which cleaves 5’ end
  • Lyase cleaves 3’ end
  • DNA polymerase B fills in gap
  • DNA ligase seals it
  • important in repair of spontaneous deamination
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Mismatch repair

A

Newly synthesized strand is recognized, mismatched nucleotides removed and gap is filled and resealed

  • Defected in HNPCC
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Nonhomologous end joining

A

Brings together 2 ends of DNA fragments to repair double stranded breaks

  • NO requirement for homology
  • mutated in ataxia telangiectasia
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

mRNA start codons

A

AUG

  • Eukaryotes: methionine ( can be removed)
  • Prokaryotes: formylmethionine (f-met)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

mRNA stop codons

A
  • UGA
  • UAA
  • UAG
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Regulation of gene expression:

Promoter

A

Site where RNA pol and other TR find to DNA upstream of gene locus

  • TATA box
  • CAAT
  • promoter mutation commonly results in dramatic decrease in gene expression
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Regulation of gene expression:

Enhancer

A

Stretch of DNA that alters gene expression by binding transcription factors

  • Enhancers and silencers may be located close or far from genes it regulates
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Regulation of gene expression:

Silencer

A

Site where repressors bind

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

RNA polymerase

A
  • RNA pol I: rRNA
  • RNA pol II: mRNA
  • RNA pol III: tRNA

RNA poly II opens DNA at promoter site

a-amanitin (death mushroom): inhibits RNA pol II– severe hepatotoxicity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

RNA processing

A

Initial RNA transcript is heterogenous nuclear RNA (hnRNA) and is then modified to become mRNA

  • 5’ cap
  • poly A tail (AAUAAA= polyadenylation signal)
  • splicing of introns

mRNA is transported out of nucleus into cytosol where it is translated

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

Splicing of pre-mRNA

A
  1. Primary transcript combines with small nuclear ribonucleoproteins (snRNPs) and other proteins to form spliceosome
  2. Loop intermediate is generated
  3. Loop is released to remove intron and join exons

ANtibodies to spliceosomal snRNPS (anti-smith antibodies) are highly specific for SLE

Anti-U1 RNP are highly associated with mixed connective tissue disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

Introns

A

Introns are intervening NON-coding regions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

Exons

A

Contain actual genetic information.

Exons are Expressed

  • abnormal splicing variants are implicated in some genetic disorders ( B-thalassemia)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

tRNA structure

A
  • Clover-leaf form
  • anti-codon end, 3’ aminoacyl end
  • amino acid is bound to 3’ end of tRNA
  • CCA= can carry amino acid
  • T-arm: necessary for tRNA ribosome binding
  • D-arm: necessary for tRNA recognition by correct aminoacyl tRNA synthetase
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

tRNA charging

A

Aminoacyl-tRNA synthetase checks amino acid before and after it binds to tRNA

  • incorrect: hydrolyzed
  • mischarged= reads usual codon but inserts wrong amino acid
  • Aminoacyl-tRNA synthetase adn binding of charged tRNA to the codon are responsible for accuracy of amino acid selection
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

tRNA wobble

A

Accurate base pairing is required only in the first 2 nucleotide positions of an mRNA codon so codons differing int he 3rd wobble position may code for the same tRNA /amino acid

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

Protein Synthesis:

  • Intiation
  • Elongation
  • Termination
A
  • Initiation: initiated by GTP hydrolysis.
    • Initiation factors assemble 40s ribosomal subunit with tRNA and are released when 60s unit assemble with the complex
  • Elongation:
    • amino-acyl tRNA binds to A site
    • rRNA (ribozyme) catalyzes peptide bond formation, transfer polypeptide to amino acid in A site
    • Ribosome advances 3’ nucleotides towards 3’ end, moving peptidyl RNA to P site (translocation)
  • Termination: stop codons recognized by release factor and completed poly peptide is released
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

Post-translational modifications

A
  • Trimming: removal of N or C terminal
  • Covalent alterations: phosphorylation, glycosylation, hydroxlation, methylation, etc
  • Chaperone proteins: protein folding
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

Tumor suppressor

A

p53 and hypophosphorylated Rb

  • inhibit G1 to S progression
  • mutation leads to unrestrained cell division
  • Li Fraumeni syndrome
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

Permanent cells

A

Remain in G0, rengerate from stem cells

  • Neurons, skeletal and cardiac muscle, RBC
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

Stable cells

A

Enter G1 from G0 when stimulated

  • Hepatocytes, lymphocytes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

Labile cells

A

Never go to G0

  • divide rapidly
  • most affected by chemotherapy
  • Bone marrow, gut epithelium, skin, germ cells
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

Rough Endoplasmic Reticulum

A

site of synthesis of secretory proteins

  • Nissl bodies (RER in neurons): synthesize peptide neurotransmitters for secretion
  • Mucus secreting goblet cells and anti-body secreting plasma cells are rich in RER
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

Smooth Endoplasmic Reticulum

A

Site of steroid synthesis and detoxification of drugs and poisons

  • Lacks surface ribosomes
  • liver hepatocytes and steroid hormone producing cells of adrenal cortex and gonads are rich in SER
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

Golgi

A

Distribution center for proteins and lipids from ER

  • Modifies N-oligosaccharides on asparagine
  • Adds O-oligosaccaride on serine and threonine
  • adds Mannos 6 phosphate to proteins (to lysosome)
  • Endosomes: send things to lysosomes for destruction or to Golgi for further use
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

I cell disease

A

Inclusion cell disease

  • Inherited lysosomal storage disease
  • defect in phosphotransferase
  • failure of golgi to phosphorylate mannose resides on glycoproteins
  • proteins are secreted extracellularly rather than to lysosomes
  • results in coarse facial features, clouded corneas, restricted joint movement, high plasma levels of lysosomal enzymes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

Signal recognition particle

A

Cytosolic ribonucleoprotein that traffics proteins from ribosome to RER

  • absent: proteins accumuate in the cytosol
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

Vesicular trafficking proteins

A

COP I:

  • Golgi to golgi
  • Golgi to ER

COP II

  • Golgi to golgi (anterograde)
  • ER to golgi

Clathrin

  • trans golgi to lysosomes
  • plasma membrane to endosomes (receptor mediated endocytosis)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
48
Q

Peroxisome

A

Membrane enclosed organelle involved in catabolism of very long chain fatty acid, branched chain fatty acid and amino acid

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

Proteosome

A

Protein complex that degrades damaged or Ubiquinated protens

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
50
Q

Microtubules

A

Composed of helical array of polymerized heterodimers of alpha and beta tubulin

  • each dimer has 2 GTp bound
  • incorporated into flageallal, cilia, mitotic spindles
  • involved in axoplasmic transport in neurons

Drugs that act on microtubules

  • Mebendazole
  • Griseofulvin
  • Colchicine
  • Vincristine/Vinblastine
  • Paclitaxel
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
51
Q

Molecular Motor Proteins

A

Transport cellular cargo toward opposite ends of microtubule tracks

  • Dynein: retrograde to microtubule ( + to -)
  • Kinesin: anterograde to microtubule ( - to +)
52
Q

Cilia Structure

A

9 +2 arragement of microtubules

53
Q

Kartagener Syndrome

A
  • Primary ciliary dyskinesis
    • Immotile cilia due to dynein arm defect
    • results in male and female infertility
    • increase risk of ectopic pregnancy
    • can cause bronchiectasis, recurrent sinusitis, situs inversus
54
Q

Intermediate filiament

Immunohistochemical stains

  • Vimentin
  • Desmin
  • cytokeratin
  • GFAP
  • Neurofilament
A
  • Vimentin: connective tissue
  • Desmin: Muscle
  • cytokeratin: epithelial cells
  • GFAP: neuroGlia
  • Neurofilament: neurons
55
Q

Sodium Potassium pump

A

located on plasma memebrane with ATP site on cytosolic side

  • 3 NA out
  • 2 K+ in
  • Oubain inhibits by binding K+ site
  • Cardiac glycosides ( digoxin adn digitoxin) inhibit NaK ATPase which leads to inhibition of Na/Ca exchange ( increase Ca leads to increase contractility)
56
Q

Collagen

A
  • Type I: Bone, Skin, Tendon, (Osteogenesis imperfecta)
  • Type II: Cartilage, vitreous body, nucleus pulposus
  • Type III: Reticulin: skin, blood vessels, uterus, fetal tissue, granulation tissue
  • Type IV: Basement membrane (Alport syndrome)
57
Q

Collagen synthesis

A
  1. Synthesis (RER): translation of collagen alpha chain (Gly-X-Y, proline/lysine)
  2. Hydroxylation of specific proline and lysine residues (requires vitamin C)
  3. Glycosylation of pro-alpha-chain hydroxylysine residues). Formation of procollagen (triple helix of alpha chain)
  4. Exocytosis: Exocytosis of procollagen into extracellular space
  5. Proteolytic processing: cleavage of disulfide terminal regions to make tropocollagen
  6. Cross-link: makes collagen fibrils (problems lead to Ehlers-Danlos)
58
Q

Osteogenesis Imperfecta

A

Genetic bone disorder

(brittle bone disease)

  • Autosomal dominant with decreased production of normal type I collagen
  • multiple fractures with minimal trauma
  • Blue Sclera due to translucency of connective tissue over choroidal veins
  • Hearing loss (abnormal ossicles)
  • Dental imperfections
59
Q

Ehlers-Danlos

A

Faulty collagen synthesis causing hyperextensible skin, tendency to bleed and h_ypermobile joints_

  • may be associated with joint dislocation, berry and aortic aneurysms, organ rupture
  • Classic type: mutation in Type V collagen
  • Vascular type: mutation in Type III collagen
60
Q

Menkes Disease

A

connective tissue disease caused by impaired copper absorption and transport

  • Leads to decrease activity of lysyl oxidase
  • results in brittle, kinky hair, growth retardation and hypotonia
61
Q

Elastin

A

Stretchy protein within skin, lungs, large arteries, elastic ligaments, vocal cords, ligamenta flava

  • rich in proline, glycine,
  • broken down by elastase which is normally inhibited by alpha 1 anti-trypsin
62
Q

Marfan syndrome

A

caused by defect in fibrillin ( glycoprotein that forms a sheath around elastin)

63
Q

PCR

A

Amplify a desired fragment of DNA

  1. Denaturation: DNA is denatured by heating to generate 2 separate strands
  2. Annealing: premade DNA primers anneal to specific sequence on each strand to be amplified
  3. Elongation: heat stable DNA polymerase replicates the DNA sequence following each primer
  4. agarose gel electrophoresis: used for size separation of PCR products compared to DNA ladder
64
Q

Southern Blot

A
  1. DNA sample is enzymatically cleaved into smaller pieces
  2. electrophoresed on a gel
  3. transfered to filter
  4. filter is soaked in denaturant and exposed to DNA probe that recognizes its complementary strand
  5. filter exposed to film to visualize DNA
65
Q

Northern blot

A

similar to Southern blot, but RNA sample is used to study mRNA levels ( gene expression)

66
Q

Western Blot

A
  1. Protein is separated using gel electrophoresis and transferred to filter
  2. labled antibody is used to bind to relevant protein
67
Q

South-western blot

A

Identifies DNA-binding proteins (transcription factors) using labeled oligonuclotide proteins

68
Q

Microarrays

A

Thousands of nucleic acid sequences are arranged on grids

  • DNA is hybridized to the chip and scanner detects relative amounts of complementary binding
  • used to profile gene expression
  • able to detect SNP and copy number variations
69
Q

ELISA

A

Used to detect the presence of either a specific antigen (direct) or specific antibody (indirect) in a patient’s peripheral blood

  • Indirect: uses a test antigen to see if a specific antibody is present in pts blood. secondary antibody coupled to a label is used to detect the first antibody
  • Direct: uses a test **antibody **to see if a specific antigen is present in the patient’s blood. secondary antibody coupled to a label used to detect antigen
70
Q

FISH

A

Fluorescent DNA or RNA probe to specific gene site of interest on chromosome

  • used for specific localizaton of genes and direct visualization of anomalies when deletion is too small to be seen on karyotype
71
Q

Cloning methods

A

Production of recombinant DNA molecule that is self perpetuating

  • Isolate eukaryotic mRNA of itnerest
  • Expose mRNA to reverse transcriptase to produce cDNA
  • Insert cDNA fragment into bacterial plasmids
  • transform recombinant plasmid into bacteria
  • surviving bacteria on antibiotic medium produce cDNA
72
Q

Cre-lox System

A

Inducibly manipulate genes at specific developmental point

73
Q

RNA interference (RNAi)

A

dsRNA synthesized that is complementary to mRNA sequence of interest.

DsRNA promote degradation of target mRNA knocking down gene expression

74
Q

Karyotyping

A

Process in which metaphase chromosomes are stained, ordered and numbered according to morphology, size, arm length ratio and banding pattern

  • can be preformed on blood, bone marrow, amniotic fluid, placental tissue
  • used to diagnose chromosomal imbalances, autosomal trisomies, sex chromosome disorders
75
Q

Co-dominance

A

Both alleles contribute to the phenotype of the heterozygote

76
Q

Variable Expressivity

A

Phenotype varies among individuals with same genotype

77
Q

Incomplete Penetrance

A

Not all individuals with a mutant genotype show the mutant phenotype

78
Q

Pleiotrophy

A

One gene contributes to multiple phenotyic effects

79
Q

Anticipation

A

Increased severity or earlier onset of disease in succeeding generations

80
Q

Loss of heterozygosity

A

If a pt inherits or develops a mutation in a tumor suppressor gene, the complementary allele must be deleted or mutated before cancer develops

(not true of oncogenes)

81
Q

Dominant negative mutation

A

Exerts a dominant effect. A heterozygote produces a nonfunctional altered protein that also prevents the normal gene product from functioning

82
Q

Linkage disequilibrium

A

Tendency for certain alleles at 2 linked loci to occur together more often than expected by chance.

  • Measured in a population not in a family
  • varies in different populations
83
Q

Mosaicism

A

Presence of geneticlly distinct cell lines in the same individual

  • arises from mitotic errors after fertilization
  • somatic mosaicism: mutation propagate through multiple tissues or orans
  • Gonadal mosaicism: mutation only in egg or sperm cells
84
Q

Locus Heterogeneity

A

Mutations at different loci can produce similar phenotype

85
Q

Allelic heterogeneity

A

Different mutations in the same locus produce the same phenotype

86
Q

Heteroplasmy

A

Presence of both normal and mutated mtDNA, resulting in variable expression in mitochondrial inherited disease

87
Q

Uniparental disomy

A

offspring recieves 2 copies of a chromosome from 1 parent and no copies from the other

  • Heterodisomy (heterozygous) indicates a meiosis I error
  • Isodisomy (homozygous) indicates a meiosis II error or postzygotic chromosomal duplication of one of a pair of chromosomes and loss of the other of the original pair
88
Q

Hardy Weinberg population genetics

A

If a population is in Hardy-Weinberg equilibrium and p and q are different frequencies of separate alleles

P2+2pq+q2= 1

  • p2 is freq. of homozygous for p
  • q2 is freq of homozygous for q
  • 2pq is freq of heterozygosity
  • Frequency of x-linked recessive disease in males is q and in females = q2

Assumptions

  • no mutation occuring at the locus
  • natural selection is not occuring
  • completely random mating
  • no net migration
89
Q

Imprinting

A

at some loci, only one allele is active

  • other is inactive ( imprinted/inactivated by methylation)
  • with one allele active, deletion of active allele leads to disease
  • Prader willi
  • Angelman syndrome
90
Q

Prader Willi Syndrome

A

Maternal imprinting

  • Gene from mom is normally silent
  • Paternal gene is deleted/ mutated
  • results in hyperphagia, obesity, intelectual disability, hypogonadism and hypotonia
91
Q

Angelman Syndrome

A

Paternal imprinting

  • gene from dad is silent
  • Maternal gene is deleted or mutated
  • results in inappropriate laughter ( happy puppet)
  • seizure, ataxia, severe intellectual disability
92
Q

Autosomal dominant

A
  • often due to defects in structural genes
  • many generations
  • both male and female affected
  • often pleotrophic
93
Q

Autosomal recessive

A
  • 25% of offspring from 2 carrier affected
  • often due to enzyme deficiencies
  • usually seen in only 1 generation
  • Commonly more severe than dominant disorder
  • increase risk consanguineous families
94
Q

X-linked recessive

A
  • Sons of heterzygous mothers have a 50% chance of being affected
  • no male to male transmission
  • commonly more severe in males
  • females have to be homozygous to be affected
95
Q

x-linked dominant

A
  • Transmitted through both parents
  • mothers transmit to 50% of daughters and sons
  • fathers transmit to all daughters but no sons
  • Hypophospahtemic Rickets (vitamin D resistant rickets): inherited disorder resulting in phosphate wasting at proximal tubule
96
Q

Mitochondrial inheritance

A
  • transmitted only through mother
  • all offspring of affected females may show signs of disease
  • variable expression in a population or within a family due to heteroplasmy
  • Mitochondrial myopathies
    • present with myopathies, lactic acidosis and CNS disease
    • secondary to failure in oxidative phosphorylation
    • muscle biopsy shows “ragged red fibers”
97
Q

Autosomal Dominant Diseases

A
  • AD polycystic kidney disease (ADPKD)
  • Familial Adenomatous polyposis
  • Familial Hypercholesterolemia
  • Hereditary Hemorrhagic telangiectasia
  • Hereditary Spherocytosis
  • Huntington disease
  • Marfan syndrome
  • MEN
  • Neurofibromatosis type I
  • Neruofibromatosis type 2
  • Tuberous sclerosis
  • von Hippel-lindau disease
98
Q

Autosomal Recessive Diseases

A
  • Albinism
  • ARPKD
  • cystic fibrosis
  • glycogen storage diseases
  • hemochromatosis
  • kartagener syndrome
  • mucopolysaccharidoses (except Hunter)
  • phenylketouria
  • sicle cell anemia
  • sphingolipidoses ( except: Fabry)
  • thalassemia
  • wilsons disease
99
Q

X-linked Recessive Disorders

A
  • Bruton agammaglobulinemia
  • Wiskott Aldrich syndrome
  • Fabry disease
  • G6PD deficiency
  • Ocular albinism
  • Lesch-Nyhand syndrome
  • Duchenne and Becker muscular dystrophy
  • Hunter Syndrome
  • Hemophilia A and B
  • Ornithine transcarbamylase deficiency

(Be Wise, Fool’s GOLD Heeds Silly HOpe)

100
Q

Autosomal Trisomies

A
  • Down Syndrome (trisomy 21)
  • Edward’s syndrome (trisomy 18)
  • Patau syndromes ( trisomy 13)
101
Q

autosomal polycystic kidney disease

A
  • always bilateral
  • massive enlargement of kidneys due to multiple large cysts
  • most due to mutation in PKDI (chromosome 16)
    • 16 letters in polycystic kidney
  • or PKD2 on chromosome 4
102
Q

Familal Adenomatous polyposis

A

colon becomes covered with adenomatous polyps after puberty

  • Progresses to colon cancer unless colon is resected
  • mutation on chromosome 5 (APC gene)
    • 5 letters in polyp
103
Q

Familial Hypercholesterolemia

A

Elevated LDL due to defective or absent LDL receptor

  • Leads to severe atherosclerotic disease early in life
    • tendon xanthomas ( typically in achilles tendon)
104
Q

Hereditary Hemorrhagic telangiectasia

A

Inherited disorder of blood vessels

  • telangiectasia, recurrent epistaxis, skin discoloration, arteriovenous malformations, GI bleeding, hematuria
  • Oscler Weber Rendu syndrome
105
Q

Hereditary Spherocytosis

A

Spheroid erythrocytes due to spectrin or ankyrin defect

  • Hemolytic anemia
  • increased MCHC
  • Tx: splenectomy
106
Q

Huntington Disease

A
  • Depression, progressive demetia, choreiform movements, caudate atrophy
  • derease levels of GABA and Ach in brain
  • Gene on Chromosome 4
  • Trinuclotide repeat disorder (CAG)
  • increase repeats–> decrease in age of onset
107
Q

Marfan Syndrome

A

Fibrillin -1 gene mutation

  • connective tissue disoder affectin skeleton, heart and eyes
  • tall with long extremities, pectus excavatum, hypermobile joints, long tapering fincers and toes
  • Cystic medial necrosis of aorta –> aortic incompetence and dissecting aortic aneurysms
  • floppy mitral valve
  • subluxation of lenses, typically upward and temporally
108
Q

Multiple Endocrine Neoplasias

A
  • Characterized by familal tumors of endocrine glands
  • affects pancreas, parathyroid, pituitary, thyroid, adrenal medulla
  • MEN2A and MEN2B are associated with the Ret gene
109
Q

Neurofibromatosis Type I

Von Recklinghausen disease

A
  • Neurocutaneous disorder characterized by cafe-au-lait spots and cutaneous neurofibromas
  • Autosomal dominant
  • 100% penetrance, variable expression
  • caused by mutations in NF1 gene on Chromosome 17
    • 17 letters in von Recklinghausen
110
Q

Neurofibromatosis type 2

A
  • Bilateral acoustic schwannomas, juvenile cataracts, meningiomas and ependymomas
  • NF2 gene on chromosome 22
111
Q

Tuberous Sclerosis

A

Neurocutanous disorder with multiorgan system involvement

  • characterized by hamartomas
  • incomplete penetrance, variable expression
112
Q

Von hippel-lindau Disease

A

Characterized by development of numerous tumors, both benign and malignant

  • deletion of VHL gene (tumor suppressor) on chromosome 3
    • VHL= 3
113
Q

Cystic Fibrosis

A
  • Autosomal recessive
  • Defect in CFTR gene (chromosome 7)
  • commonly a deletion on Phe508
  • CFTR encodes an ATP gate Cl- channel that secretes Cl- in lungs and GI Tract and reabsorbs Cl- in sweat glands
  • Mutations leads to misfolder proteins that is retained in RER and not transported to cell membrane
  • leads to decrease in Cl- secretion and increase in Cl- leads to compensatory increase in Na reabsorption via ENaC
  • increases H20 reabsorption leading to abnormally thick mucus in lungs and GI tract
  • Diagnosis: increase Cl- concentratioon in sweat is diagnostic
  • Presentation
    • contraction alkalosis and hypokalemia
    • ECF water and Na loss with K+/H+ wasting
  • Complication
    • recurrent pulmonary infections, chronic bronchitis, bronchiectasis
    • pancreatic insufficiency, malabsorption, steatorrhea, nasal polyps
    • meconium ileus in newborns
    • infertility in males
    • fat soluble vitamin deficiency
  • Treatment
    • N- acetylcysteine to loosen mucus plugs
    • dornas alfa (DNAse) to clear leukocytic debri
114
Q

Duchenne MD

A
  • X-linked frameshift mutation
  • truncated dystrophin protein
  • causes accerated muscle breakdown
  • weakness begins in pelvic girdle muscles and progresses superiorly
  • pseudohypertrophy of calf muscles due to fibrofatty replacement of muscle
  • Gower maneuer: patients use upper extremity to help them stand up
  • onset before 5 years
  • Dilated cardiomyopathy common cause of death
  • Loss of dystrophin resuls in myonecrosis, increase CPK and aldolase
  • Western blot and muscle biopsy to confirm diagnosis
115
Q

Becker MD

A
  • usually x-linked point mutation in dystrophin gene ( no frameshift)
  • less severe than Duchenne
  • onset in adolescence or early adulthood
116
Q

Myotonic type I muscular dystrophy

A
  • CTG tri-nucleotide repeat expansion in DMPK gene
  • abnormal expression of myotonin protein kinase
  • myotonia, muscle wasting, frontal balding, cateracts, testincular atrophy, arrthythmia
117
Q

Fragile X syndrome

A
  • X-linked defect affecting the methylation and expression of FMRI gene
  • second most common cause of genetic intellectual disability ( after Downs)
  • Post-puberty macroorchidism ( enlarged testes)
  • long face with large jaw, large everted ears, autism, mitral valve prolapse
  • Trinucleotide repeat (CGG)
118
Q

Trinucleotide repeat expansion disorders

A
  • Fragile X Syndrome: CGG
  • Friedreich ataxia: GAA
  • Huntington disease: CAG
  • Myotonic dystrophy: CTG
119
Q

Down Syndrome

A
  • Trisomy 21
  • Intellectual disability, flat facies, prominent epicanthal folds, single palmar crease, gap between 1st 2 toes, duodenal atresia, Hirshsprung disease, concenital heart disease, ostium primum type atrial septal defect, Brushfield spots
  • associated with increase risk of ALL, AML and Alzheimers disease
  • most cases due to meiotic non-disjunction of homologous chromosomes
  • 4% of cases due to Robersonian translocation
  • 1% of cases due to mosaicism
  • First trimester
    • US increased nuchal translucency & hypoplastic nasal bone
    • serum PAPP-A decreased, free B-hCG is increased
  • Second trimester
    • decreased a-fetoprotein
    • increased B-hCG
    • decreased estradiol
    • increased inhibin A
120
Q

Edwards Syndrome

A
  • Trisomy 18
  • Severe intellectual disability, rocker bottom feet, micrognathia, low set ears, clenched hands, prominent occiput, congenital heart disease
  • Death usually within 1 year of birth
  • First trimester
    • Decreased PAPP-A and free B-hCG
    • decreased a-fetoprotein
    • decreased B-hCG
    • decreased estradiol
    • normal inhibin A
121
Q

Patau syndrome

A
  • Trisomy 13
  • Severe intellectual disability
  • rocker bottom feet, micropthalmia, microcephaly, cleft lip/palate, holoprosencephaly, polydactylyl, congenital heart disease
  • death usually in first year of birth
  • First trimester
    • decrease free B- hCG
    • decreased PAPP-A
    • increased nuchal translucency
122
Q

Robertsonian Translocation

A

non-reciprocal chromosomal translocation that commonly involves chromosomes 13, 14,15,21, 22

  • occurs when the long arm of 2 acrocentric chromosomes fuse at the centromere and the 2 short arms are lost
  • Unbalanced translocations can result in miscarriage, stillbirth, and chromosomal imbalance
123
Q

Cri-du-chat syndrome

A

Congenital microdeletion of short arm of chromosome 5

  • 46, AA or XY, 5p-
  • Microcephaly, moderate to severe intellectual disability, high pitched crying/ mewing, epicanthal folds, cardiac abnormalities (VSD)
124
Q

Williams Syndrome

A

Congenital microdeletion of long arm of chromosome 7

  • deleted region includes elastin gene
  • “elfin” facies, intellectual disability, hypercalcemia (increased sensitivity to vitamin D)
  • well developed verbal skills, extreme friendliness with strangers, cardiocascular problems
125
Q

22q11 deletion

A
  • due to aberrant development of 3rd & 4th branchial pouches
  • Presentation: Catch 22
    • Cleft palate
    • Abnormal facies
    • Thymic aplasia
    • Cardiac defects
    • Hypocalcemia (2* to Parathyroid aplasia)
  • Microdeletion of chromosome 22q11
  • DiGeorge Syndrome: thymic, parathyroid, cardiac defects
  • Velocardiofacial syndrome: palate, facial, cardiac defects
126
Q
A

First Aid (8 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions