Inheritance Patterns Flashcards
X-Linked Recessive Disorders
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”
Process of Translation
1) Activation of the monomer
2) Initiation
3) Elongation
4) Termination
5) Processing the polymer
Compounds Affecting Protein Synthesis
-Diphtheria toxin
-Antibiotics that inhibit initiation and elongation
Diphtheria toxin
Inactivation of EF-2 by ADP-ribosylation
Streptomycin (aminoglycoside)
Prevents assembly of ribosome (binds to 30s subunit)
Tetracycline
4 (tetra) ring (cyclic) structure
-Block elongation by preventing aminoacyl-tRNA access to the A-site
Erythromycin (macrolide)
Binds to the 50S subunit of the complete (70S) ribosome
-Blocks ribosome translocation
Chloramphenicol
Inhibits peptidyl transferase activity in prokaryotes
-At high levels, may inhibit mitochondrial translation
Cycloheximide
Inhibits eukaryotic peptidyl transferase activity
Puromycin
Causes premature termination of translation in both prokaryotes and eukaryotes
Types of post-translational modifications
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)
Glycosylation
Alters the properties of proteins, changing their stability, solubility, & physical bulk
O-linked Glycosylation
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
N-linked Glycosylation
Carbohydrate chains attached to the amide nitrogen of Asn residue.
-Occurs in the ER & Golgi. In ER, modulates folding of proteins
C-peptide
-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
Protein Denaturation By:
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
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?
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.
Mitochondrial Inheritance
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
MELAS
Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes (Mitochondrial inheritance and heteroplasmy)
Digenic disorders
Retinitis pigmentosa
Imprinting
Prader Willi syndrome
Angelman syndrome
*Parent of origin effect
Triplet repeat disorders with anticipation
Huntington disease
Myotonic dystrophy
**First 2 are autosomal dominant
-Fragile X syndrome (X-linked)
Genetic Detection Methods: Direct (Hypothesis Driven)
-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)
Methods that may query (interrogate) the entire genome
-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)
Hybridization
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)
RFLP
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
Autosomal Dominant Disorders
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)
Gain of function mutations
Result from increased levels of gene expression or gene activity or development of a new function of the gene (Ex. Huntington disease, Achondroplasia)
Autosomal Recessive Disorders
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”
Friedrich Ataxia Triplet Repeat Region
GAA (ataxia with two AAs): in an intron resulting in formation of heterochromatin
Fragile X syndrome triplet repeat region
CGG (G in fragile corresponds with promoter region of the gene)
Huntington disease triple repeat region
CAG (Codes for glutamine: AG present in Huntington’s Disease (A in Disease, G in Huntington’s and CAG requires motor function: neurological defects)
Myotonic Dystrophy triple repeat region
CTG (MyoTonic dystrophy) on intron
