Inheritance Patterns

Question 1

X-Linked Recessive Disorders

Answer 1

1) Dystrophin associated muscular dystrophy
2) Glucose 6-phosphate dehydrogenase (G6PD) deficiency
3) Hemophilia A and B result in bleeding tendencies
4) Lesch-Nyhan syndrome [Hypoxanthine Guanine Phosphoribosyl transferase (HGPRT) deficiency]
-Causes hyperuricemia, gout & self mutilation
5) Red-green color blindness/deficiency (non-lethal)
6) X-linked SCID (defect in the SCIDX1 gene)
7) Rett Syndrome
8) Incontinentia Pigmenti
Mnemonic: “Lucky Girls Have Really Dirty Butt Sex”

Question 2

Process of Translation

Answer 2

1) Activation of the monomer
2) Initiation
3) Elongation
4) Termination
5) Processing the polymer

Question 3

Compounds Affecting Protein Synthesis

Answer 3

-Diphtheria toxin
-Antibiotics that inhibit initiation and elongation

Question 4

Diphtheria toxin

Answer 4

Inactivation of EF-2 by ADP-ribosylation

Question 5

Streptomycin (aminoglycoside)

Answer 5

Prevents assembly of ribosome (binds to 30s subunit)

Question 6

Tetracycline

Answer 6

4 (tetra) ring (cyclic) structure
-Block elongation by preventing aminoacyl-tRNA access to the A-site

Question 7

Erythromycin (macrolide)

Answer 7

Binds to the 50S subunit of the complete (70S) ribosome
-Blocks ribosome translocation

Question 8

Chloramphenicol

Answer 8

Inhibits peptidyl transferase activity in prokaryotes
-At high levels, may inhibit mitochondrial translation

Question 9

Cycloheximide

Answer 9

Inhibits eukaryotic peptidyl transferase activity

Question 10

Puromycin

Answer 10

Causes premature termination of translation in both prokaryotes and eukaryotes

Question 11

Types of post-translational modifications

Answer 11

1) Protein Folding (formation of disulphide bridges)
2) Covalent alterations (phosphorylation, glycosylation, hydroxylation)
3) Proteolytic processing (trimming, zymogen activation)
4) Addition of prosthetic groups (Heme of hemoglobin)
5) Prenylation (lipid anchoring, farnesylation)
6) Protein degradation (ubiquitination and degradation by the proteasome complex)

Question 12

Glycosylation

Answer 12

Alters the properties of proteins, changing their stability, solubility, & physical bulk

Question 13

O-linked Glycosylation

Answer 13

Carbohydrate chain attached to the OH group of Ser/Thr
-Glycan groups always face extracellular side
-Occurs only after the protein reaches the Golgi Apparatus

Question 14

N-linked Glycosylation

Answer 14

Carbohydrate chains attached to the amide nitrogen of Asn residue.
-Occurs in the ER & Golgi. In ER, modulates folding of proteins

Question 15

C-peptide

Answer 15

-essential for proper insulin folding
-C-peptide is good indicator of insulin production and secretion because its (C-peptide) half-life in the plasma is longer than that of insulin

Question 16

Protein Denaturation By:

Answer 16

1) Heat
2) Extremes in pH
3) Detergents: disrupt hydrophobic interactions
4) Reduction of disulphide bonds using mercaptoethanol and other reducing agents
5) Organic solvents
6) Chaotropic: urea/guanidium have a strong capacity to form hydrogen bonds

Question 17

A 20 year old woman with hyperlipoproteinemia type I was identified to have pathogenic mutations of the lipoprotein lipase gene. Gene analysis shows a Glu242Lys on one copy and Leu58Asp substitution on the second
copy of the gene. Which term describes this patient?

Answer 17

Compound heterozygote-This is describing an affected individual (Autosomal recessive enzyme deficiency disorder). They are two different mutations on the 2 copies of the gene coding lipoprotein lipase.

Question 18

Mitochondrial Inheritance

Answer 18

Mitochondria are inherited from the mother
-All offspring of an affected female are affected
-Only females transmit the disorder
-Affected father does not transmit the disorder to his children
-Both male and female children of an affected female are affected

Question 19

MELAS

Answer 19

Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes (Mitochondrial inheritance and heteroplasmy)

Question 20

Digenic disorders

Answer 20

Retinitis pigmentosa

Question 21

Imprinting

Answer 21

Prader Willi syndrome
Angelman syndrome
*Parent of origin effect

Question 22

Triplet repeat disorders with anticipation

Answer 22

Huntington disease
Myotonic dystrophy
**First 2 are autosomal dominant
-Fragile X syndrome (X-linked)

Question 23

Genetic Detection Methods: Direct (Hypothesis Driven)

Answer 23

-Southern-RFLP, PCR-RFLP, PCR sizing, ASO blot
-FISH (tag a specific place on a chromosome with a probe)
-Northern, Western
-Sanger Sequencing (one run at a time)

Question 24

Methods that may query (interrogate) the entire genome

Answer 24

-Karyotype (G-banding)
-Microarray: array CGH, SNP chip, expression arrays
-Spectral karyotype (paint each chromosome a different color)
-Next generation sequencing (multiplex): one gene, panel of related genes, all of the exomes (whole exome sequencing; WES), all of the genome (whole genome sequencing; WGS)

Question 25

Hybridization

Answer 25

Annealing of ssDNA probe to complementary ssDNA
-Sequencing (primer)
-Southern blots (DNA)
-Northern blots (RNA)
-RFLP (analysis)
-Allele specific oligonucleotide (ASO probes)
-Western blots (Protein)

Question 26

RFLP

Answer 26

Restriction Fragment Length Polymorphism
-Single base pair change in the DNA may cause creation or destruction of a restriction site
-Clinician (or scientist) must know this DNA variation to do the test
-Diagnosis of patient with suspected Sickle Cell Anemia

Question 27

Autosomal Dominant Disorders

Answer 27

1) Familial Hypercholesterolemia (Decrease in LDLR, haploinsufficiency)
2) Huntington Disease
3) Myotonic Dystrophy
4) Marfan Syndrome (FBN1, haploinsufficiency)
5) Osteogenesis Imperfecta (COL1A1, COL1A2, haploinsufficiency)
6) Achondroplasia (FGFR3)
7) Neurofibromatosis type 1 (NF1)
8) Acute intermittent porphyria (AIP: iron deficiency, anemia)

Question 28

Gain of function mutations

Answer 28

Result from increased levels of gene expression or gene activity or development of a new function of the gene (Ex. Huntington disease, Achondroplasia)

Question 29

Autosomal Recessive Disorders

Answer 29

1) Cystic Fibrosis
2) Sickle Cell Anemia
3) Phenylketonuria
4) Tay-Sachs Disease
5) Hemochromatosis
6) Galactosemia
7) Alpha 1 antitrypsin deficiency (AATD)
8) SCID (X-linked)
Mnemonic: “CRAZY HAGS CAST Potions and Hexes” or “CHAP GETS CASH”

Question 30

Friedrich Ataxia Triplet Repeat Region

Answer 30

GAA (ataxia with two AAs): in an intron resulting in formation of heterochromatin

Question 31

Fragile X syndrome triplet repeat region

Answer 31

CGG (G in fragile corresponds with promoter region of the gene)

Question 32

Huntington disease triple repeat region

Answer 32

CAG (Codes for glutamine: AG present in Huntington’s Disease (A in Disease, G in Huntington’s and CAG requires motor function: neurological defects)

Question 33

Myotonic Dystrophy triple repeat region

Answer 33

CTG (MyoTonic dystrophy) on intron