Diseases Flashcards
Parkinson’s Disease
Parkin, an E3 ubiquitin protein ligase
α-Synuclein, a substrate for Parkin that can produce insoluble protein aggregates in selected regions of the brain
Angelman’s Disease
UBE3A: deletion of this E3 ligase contributes to the
mental retardation observed in Angelman syndrome
Hereditary Breast and Ovarian Cancer
BRCA1 and BRCA2: components of an E3 ubiquitin ligase that activate proteins involved in DNA repair (a non-traditional role for ubiquitination)
Hereditary tumors of the retina, brain, kidney and others tissues
VHL (von Hippel-Lindau protein): a component of an E3 ligase complex that targets HIF, a transcription factor that promotes angiogenesis
Prader-Willi Syndrome
Deletion of 15q11-q13 in paternal gene results in disease because maternal gene is imprinted off (methylated)
Truncal obesity, hypogonadism, small hands, short stature and mental retardation
Angelman Syndrome
Deletion of 15q11-q13 in maternal copy results in disease because paternal copy is imprinted off (methylated)
Wide stance and position of arms, short stature, mental retardation, spasticity and seizures
Myotonic dystrophy
autosomal dominant, muscle wasting, cataracts, myotonia, hypersomnia, insulin resistance
Female aneuploidies
Turner syndrome- monosomy X (45,X) Trisomy X (47,XXX)
Male aneuploidies
Klinefelter syndrome (47,XXY and 48XXXY) 47,XYY
Causes of aneuploidies
Nondisjunction during meiosis I- leads to two different copies
Nondisjunction during meiosis II- leads to two of the SAME copies
Patau Syndrome
Trisomy chromosome 13
1/22,700 live births
Down Syndrome
Trisomy 21
1/830 live births
Edward Syndrome
Trisomy 18
1/7500 live births
Digenic Retinitis Pigmentosa
Simplest example of multigenic trait—determined by additive effect of genotypes at multiple loci
No known environmental factors
2 photoreceptor proteins associate noncovalently in photoreceptors in retina: Peripherin and ROM1
Mutants of both must be present to cross threshold of cell damage, photoreceptor death and loss of vision
Hirschsprung Disease (HSCR)
Developmental abnormality of parasympathetic nervous system in gut; 1/5000
Affects ganglion cells of colon no peristalsis, severe constipation, symptoms of intestinal obstruction, massive colon dilation (megacolon) proximal to aganglionic segment
Complex genetics:
-relative risk in siblings high: λs about 200
-but MZ twins not show perfect concordance
-can occur through multiple generations, affect multiple siblings or both
Loss of a number of different genes can cause disease (locus heterogeneity): different forms behave as dominant, recessive or multigenic disorder (but risks not 50% or 25%)
males: 2-fold higher risk compared with females in same family
Type 1 IDDM (insulin dependent diabetes)
Develops in childhood, autoimmune disease with a strong genetic component
MHC locus plays an important role with certain haplotypes that predispose for disease, allow since siblings with the same haplotype have lower concordance than MZ twins there must be other genes that play a role in the disease
Idiopathic Cerebral Vein Thrombosis
Clots form in venous system of brain, cause catastrophic occlusion of cerebral veins in absence of inciting event (ie infection or tumor)
Affects young adults
Rare, but with high mortality rate: 5-30%
Three relatively common factors (cumulative)
-2 genetic + 1 environmental
-each individually increase risk
Mutant alles include factor V and prothrombin (oral contraceptive combined with either of these alleles increases risk)
Alzheimer disease
Fatal neurodegenerative disease; affects 1-2% of US; most common cause of dementia in elderly; responsible for > half of all cases of dementia
Most significant risk factors: age, gender, family history
E4 allele of apolipoprotein E (APOE) are 2 to 3x more likely to have AD
common form-late onset (>60yrs); no obvious Mendelian inheritance; yes familial aggregation and elevated relative risk ratio
Schizophrenia
possibly multi genetic, usage of recurrence risk table
Bipolar disorder
possibly multi genetic, usage of recurrence risk table
Anencephaly and neural tube defects
Lack of folic acid leading to under development of brain and neural tube (ex. spina bifida)
Multi Drug Resistant Protein (ABC transporter)
Pumps numerous drugs out of the cytosol
Expression increased in numerous cancers, making them resistant to drugs targeting them
Cystic Fibrosis Transmembrane conductance Regulator protein (CFTR)
Cl- channel that transports Cl- from the cell. When defective, these ions are trapped in the cell. This attracts more cations, because the electrochemical gradient for these ions changes. More ions in general in the cytoplasm induces water to enter the cell through osmosis. Its departure from the extracellular space induces a thick, pathological mucus, especially in lungs
Plasmodium falciparum (Malaria)
Utilizes an ABC transporter to pump chloroquine, an antimalarial drug, out of the disease causing protist
