Diseases

Question 1

Parkinson’s Disease

Answer 1

Parkin, an E3 ubiquitin protein ligase

α-Synuclein, a substrate for Parkin that can produce insoluble protein aggregates in selected regions of the brain

Question 2

Angelman’s Disease

Answer 2

UBE3A: deletion of this E3 ligase contributes to the

mental retardation observed in Angelman syndrome

Question 3

Hereditary Breast and Ovarian Cancer

Answer 3

BRCA1 and BRCA2: components of an E3 ubiquitin ligase that activate proteins involved in DNA repair (a non-traditional role for ubiquitination)

Question 4

Hereditary tumors of the retina, brain, kidney and others tissues

Answer 4

VHL (von Hippel-Lindau protein): a component of an E3 ligase complex that targets HIF, a transcription factor that promotes angiogenesis

Question 5

Prader-Willi Syndrome

Answer 5

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

Question 6

Angelman Syndrome

Answer 6

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

Question 7

Myotonic dystrophy

Answer 7

autosomal dominant, muscle wasting, cataracts, myotonia, hypersomnia, insulin resistance

Question 8

Female aneuploidies

Answer 8

Turner syndrome- monosomy X (45,X)
Trisomy X (47,XXX)

Question 9

Male aneuploidies

Answer 9

Klinefelter syndrome (47,XXY and 48XXXY)
47,XYY

Question 10

Causes of aneuploidies

Answer 10

Nondisjunction during meiosis I- leads to two different copies
Nondisjunction during meiosis II- leads to two of the SAME copies

Question 11

Patau Syndrome

Answer 11

Trisomy chromosome 13

1/22,700 live births

Question 12

Down Syndrome

Answer 12

Trisomy 21

1/830 live births

Question 13

Edward Syndrome

Answer 13

Trisomy 18

1/7500 live births

Question 14

Digenic Retinitis Pigmentosa

Answer 14

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

Question 15

Hirschsprung Disease (HSCR)

Answer 15

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

Question 16

Type 1 IDDM (insulin dependent diabetes)

Answer 16

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

Question 17

Idiopathic Cerebral Vein Thrombosis

Answer 17

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)

Question 18

Alzheimer disease

Answer 18

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

Question 19

Schizophrenia

Answer 19

possibly multi genetic, usage of recurrence risk table

Question 20

Bipolar disorder

Answer 20

possibly multi genetic, usage of recurrence risk table

Question 21

Anencephaly and neural tube defects

Answer 21

Lack of folic acid leading to under development of brain and neural tube (ex. spina bifida)

Question 22

Multi Drug Resistant Protein (ABC transporter)

Answer 22

Pumps numerous drugs out of the cytosol

Expression increased in numerous cancers, making them resistant to drugs targeting them

Question 23

Cystic Fibrosis Transmembrane conductance Regulator protein (CFTR)

Answer 23

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

Question 24

Plasmodium falciparum (Malaria)

Answer 24

Utilizes an ABC transporter to pump chloroquine, an antimalarial drug, out of the disease causing protist

Question 25

Cystinuria

Answer 25

individuals have genetic defect in amino acid transporter responsible for removing cystine (cysteine dimers) causing the development of cystine stones in their bladders