Unit 2 - Week 2 Flashcards
______ is characterized by severe anemia in which RBCs are destroyed before being released into circulation.
Thalassemia Major
_______ can detect recognized microdeletions, recognized chromosomal rearrangements, and gene copy numbers; can be useful in diagnosing aneuploidies prenatally
FISH
_______ is less soluble than HbA and tends to form crystals
HbC
_______ are mutations common in hemoglobinopathies in Africa
alpha, beta-thal, C, and S
_______ are mutations common in hemoglobinopathies in East Mediterranean.
beta-thal and S
_______ are mutations common in hemoglobinopathies in Southeast Asia
alpha, beta-thal, and E
_______ are mutations common in hemoglobinopathies in West Pacific
Alpha, beta-thal, and E
_______ are qualitative hemoglobinopathies.
HbS, HbC, and HbE
_______ are quantitative hemoglobinopathies.
Thalassemias
_______ can detect aneuploidies, chromosomal deletions, duplications, or insertions of moderate to large size (>3-5 Mb), rearrangements
Chromosome Analysis
_______ can detect aneuploidies, unbalanced chromosomal rearrangements, chromosome deletions (>200kb), and chromosomal duplications (>400kb)
CMA
_______ can detect mutations in known genes, polymorphic variants, small deletions/insertions (~1-100nt); ideal for looking at sequence of known disease gene
DNA sequencing
_______ cannot detect deletions or rearrangements not tested for, duplications in gene regions, point mutations and small deletions
FISH
_______ cannot detect deletions/duplications below the limit of resolution, nucleotide mutations, balanced chromosomal rearrangement
CMA
_______ cannot detect regions of the gene outside of the region the test was designed for (specificity is frequently less than 100%); large deletions/insertions, rearrangements or most chromosomal abnormalities
DNA sequencing
_______ cannot detect single gene deletions, point mutations, small deletions, duplications, and insertions, methylation defects, and trinucleotide repeat abnormalities
Chromosome Analysis
_______ is 80% less soluble than HbA and forms long polymers that distort the shape of RBCs
HbS
_______ is a fatal condition due to homozygosity for the alpha-thalassemia-___ allele.
Hydrops fetalis; 1
_______ is caused by a decrease in β-globin synthesis due to mutations affecting transcription, RNA processing, or protein stability
Beta+ Thalassemia
_______ is caused by deletion of β-globin gene, nonsense mutation, frameshift mutation, or mutations that result in no RNA synthesis
Beta0 Thalassemia
_______ is caused by large deletions that remove the β-globin gene plus other genes in the β-cluster or LCR
Complex Thalassemia
_______ is characterized by attempted blood production results in thinning bone cortex, enlarged liver, and enlarged spleen.
Thalassemia Major
_______ is characterized by clinically normal symptoms and carrier status for the Beta-thalassemia allele.
Thalassemia Minor
_______ is less important genetically than other drug metabolism genes, because the population distribution of activity is continuous and unimodal
CYP3A
_______ is the mutational mechanism in achondroplasia
Gain of Function
_______ is the mutational mechanism in alpha-thalassemia
Loss of Function
_______ is the mutational mechanism in Charcot-Marie-Tooth Syndrome
Gain of Function
_______ is the mutational mechanism in Duchenne Muscular Dystrophy
Loss of Function
_______ is the mutational mechanism in Hemoglobin Kempsey
Gain of Function
_______ is the mutational mechanism in Hereditary Neuropathy with Predisposition to Pressure Palsy
Loss of Function
_______ is the mutational mechanism in Hereditary Persistence of Fetal Hemoglobin
Heterochromatic Expression
_______ is the mutational mechanism in Hereditary Retinoblastoma
Loss of Function
_______ is the mutational mechanism in Huntington Disease
Novel Property
_______ is the mutational mechanism in Osteogenesis Imperfecta Type 1A.
Loss of Function
_______ is the mutational mechanism in Sickle Cell Disease
Novel Property
_______ is the mutational mechanism in Turner Syndrome
Loss of Function
_______ is the step at which a mutation disrupts production of normal protein in Familial Hypercholesterolemia
Subcellular Localization
_______ is the step at which a mutation disrupts production of normal protein in Hemoglobin Kempsey
Function of correctly folded, assembled, and localized protein in normal amounts
_______ is the step at which a mutation disrupts production of normal protein in hemoglobinopathies
Protein folding
_______ is the step at which a mutation disrupts production of normal protein in Homocystinuria
Cofactor/Prosthetic Group Binding
_______ is the step at which a mutation disrupts production of normal protein in I-cell disease
Post-Translational Modification
_______ is the step at which a mutation disrupts production of normal protein in Osteogenesis Imperfecta
Assembly of monomers into a holomeric protein
_______ is the substrate for CYP2C9
Warfarin
_______ is the substrate for CYP2D6
Tricyclic Antidepressants; Codeine
_______ is the substrate for CYP3A.
Cyclosporin
_______ is the substrate for GP6D
Sulfonamide and Dapsone
_______ is the substrate for NAT
Isoniazid
_______ is the substrate for VKORC1
Warfarin
_______ is the substrate of TMPT
6-mercaptopurine; 6-thioguanine
_______ is used for small genomic deletions/insertions, probe size 100-200kb (much higher resolution than chromosome analysis).
CMA
_______ is used for suspected abnormality of chromosome number or structure.
Chromosome Analysis
_______ is used to detect chromosomal changes smaller than resolution of chromosomal analysis, works best in interphase cells.
FISH
_______ is used to find sequence changes in specific genes (must know or expect a diagnosis with an identified gene whose mutation is detectable and in a region actually sequenced.
DNA sequencing
_______ presents as disease-free since adequate levels of the γ chains are still made due to the disruption of the perinatal globin switch from γ to β
HPFH
_______-deficient individuals are susceptible to hemolytic anemia after drug exposures.
G6PD
6-mercaptopurine is metabolized by _______.
TMPT
6-thioguanine is metabolized by _______.
TMPT
alpha-thalassemia-__ allele is more common in Africa.
2
alpha-thalassemia-__ allele is more common in Southeast Asia.
1
alpha-thalassemia-__ allele is more common in the Mediterranean.
2
An individual who carries two different mutant alleles of the same gene
Compound heterozygote
Codeine is converted to ______ by _____ to be activated.
Morphine; CYP450
Codeine is metabolized by _______
CYP2D6
Cofactor administration may be a useful treatment in _______.
homocystinuria and biotinidase deficiency
Cylcosporin is metabolized by _______.
CYP3A
CYP2D6 is inhibited by _______.
Quinidine, fluoxetine, and paroxetine
CYP3A is induced by _______
Rifampin
CYP3A is inhibited by _______
Grapefruit Juice; Ketoconazole
Dapsone is metabolized by _______.
G6PD
Fluoxetine inhibits _______
CYP2D6
Grapefruit juice inhibits _______.
CYP3A
In emerging treatment models, what is a potential therapy for hemophilia?
Protein Replacement Therapy
In emerging treatment models, what is a potential therapy for Lysosomal storage diseases and alpha-1-antitrypsin?
Enzyme Replacement Therapy
Isoniazid is metabolized by _______.
NAT
Ketoconazole inhibits _______.
CYP3A
Paroxetine inhibits _______
CYP2D6
Presence of multiple common mutant alleles of the same gene in a population
Allelic heterogeneity
Quinidine inhibits _______
CYP2D6
Sandoff disease is largely caused by a defect in the ______ subunit of HexA
Beta
Sulfonamide is metabolized by _______.
G6PD
Tay-Sachs is largely caused by a defect in the ______ subunit of HexA
Alpha
Tay-Sachs is largely caused by accumulation of _______.
GM2 ganglioside
The _______ allele is characterized by a milder phenotype than β0 thalassemia because the γ gene is still active after birth instead of switching off as would normally occur
Delta-Beta Thalassemia
The following problems are challenges of which treatment therapy: expensive: deliver to proper location difficult, risk of immune response to recombinant protein, delivery across blood-brain barrier is challenging, does not always correct preexisting damage
Protein Replacement Therapy
The target of alpha1-antitrypsin (SERMINA1) is _______
elastase
Treatment dosage for children with ALL must be decreased for deficiency in _______.
TMPT
Treatment for PKU may involve _______
Low Phe diet, BH4 supplement, LNAA supplement, enzyme replacement therapy, gene therapy
Tricyclic antidipressants are metabolized by _______.
CYP2D6
Two causes of phenylketonuria are: _______
PAH defect (98%), tetrahydrobiopterin defect (1-2%)
Warfarin is metabolized by _______.
VKORC1 and CYP2C9
What are examples of compensation for novel deficits with novel drugs?
Farnesyl transferase inhibitors (progeria) and Angiotensin II Receptor Blockers (Marfan’s Syndrome)
What are examples of small molecules that may be used in treatment of genetic diseases
Imatinib (Gleevec) for CML, Pharmacologic Chaperones
What disoder is caused by mutation in the WT1 gene that results in sex reversal?
Denys-Drash and Frasier Syndromes
What disorder is caused by a mutation in FGFR3?
Achondroplasia
What disorder is caused by a mutation that decreases the body’s ability to convert testosterone to dihydrotestosterone?
5-alpha reductase deficiency
What disorder is caused by mutation in GJB2?
Non-syndromic Deafness
What disorder is characterized by ambiguous genitalia and other endocrine problems?
Congenital Adrenal Hyperplasia
What disorder is characterized by learning disabilities, speech delays, developmental delays, behavioral and emotional difficulties, autism spectrum disorders, and tall stature?
Jacob’s Syndrome
What disorder is characterized by short stature, normal intelligence, infertility, hormone dysfunction, broad chests, and low-set ears?
Turner Syndrome
What disorder is characterized by tall stature and increased risk of learning disabilities, delayed speech, delayed motor milestones, seizures, and kidney abnormalities?
Triple XXX Syndrome
What disorder is characterized by tall stature, small testes, reduced facial and body hair, infertility, hypospadias, and gynecomastia?
Klinefelter Syndrome
What disorder is characterized by the following observations in childhood: learning disabilities, delayed speech and language, tendency toward being quiet?
Klinefelter Syndrome
What disorder is characterized by the following symptoms at birth: prenatal cystic hygroma, webbed neck, puffy hands and feet, heart defects like coarctation of the aorta?
Turner Syndrome
What is the function of DHH?
Nuclear hormone receptor upregulated by WNT4 that downregulates SOX9
What is the function of FGF9?
Causes tubules from the mesonephric duct to penetrate the gonadal bridge (essential for differentiation of testes)
What is the function of RSPO1?
Coactivator of WNT4 pathway
What is the function of SF1/NR5A1?
Stimulate differentiation of Sertoli and Leydig cells
What is the function of SOX9?
Promotes production of Anti-Mullerian Hormone/Inhibits WNT4
What is the function of SRY?
Promotes production of Anti-Mullerian Hormone
What is the function of WNT4?
Extracellular signal for differentiation of the ovaries
What is the inheritance pattern of achondroplasia?
Autosomal Dominant
What is the inheritance pattern of alpha-1 antitrypsin deficiency?
Autosomal Recessive
What is the inheritance pattern of Duchenne Muscular Dystrophy?
X-linked Recessive
What is the inheritance pattern of Familial hypercholesterolemia?
Autosomal Dominant
What is the inheritance pattern of Fragile X syndrome?
X-linked Dominant
What is the inheritance pattern of Hemophilia A?
X-linked Recessive
What is the inheritance pattern of Huntington’s Disease
Autosomal Dominant
What is the inheritance pattern of Hypophosphatemic Rickets?
X-linked Dominant
What is the inheritance pattern of Kearns-Sayre?
Mitochondrial Inheritance
What is the inheritance pattern of Leber Hereditary Optic Neuropathy?
Mitochondrial Inheritance
What is the inheritance pattern of Lesch Nyhan?
X-linked Recessive
What is the inheritance pattern of Marfan Syndrome?
Autosomal Dominant
What is the inheritance pattern of MELAS (Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-like episodes)?
Mitochondrial Inheritance
What is the inheritance pattern of Myotonic Dystrophy Type 1?
Autosomal Dominant
What is the inheritance pattern of Myotonic Epilepsy with Ragged Red Fibers (MERRF)?
Mitochondrial Inheritance
What is the inheritance pattern of neurofibromatosis?
Autosomal Dominant
What is the inheritance pattern of Osteogenesis Imperfecta 1?
Autosomal Dominant
What is the inheritance pattern of phenylketonuria?
Autosomal Recessive
What is the inheritance pattern of Polycystic Kidney Disease?
Autosomal Dominant
What is the inheritance pattern of retinoblastoma?
Autosomal Dominant
What is the inheritance pattern of Rett Syndrome?
X-linked Dominant
What is the inheritance pattern of Tay-Sachs?
Autosomal Recessive
What is the screening method for HbS?
MstII Endonuclease
What is the treatment method for hyperphenylalaninemias?
Low Phe diet, BH4 supplement
What is the treatment strategy for ADA deficiency?
Replace intracellular protein
What is the treatment strategy for Hemophilia A and alpha-1-antitrypsin
Replace extracellular protein
What is the treatment strategy in Gaucher’s disease?
Target intracellular protein
What is the treatment therapy for alpha-1-antitrypsin?
Protein Replacement Therapy
What is the treatment therapy for Fabry disease?
Protein Replacement Therapy
What treatment strategy can be effective in correcting enzyme deficiencies, especially for extracellular proteins?
Protein Replacement Therapy
Which disorder is caused by a single large deletion of mtDNA?
Kearns-Sayre
Which disorder is caused by defect in Hypoxanthine phosphoribosyltransferase (HPRT1)?
Lesch-Nyhan Disease
Which disorder is caused by defect in Methyl CpG Binding protein (MECP2)?
Rett Syndrome
Which disorder is caused by deletion of mtDNA (MT-ND1, MT-ND5, MT-TH, MT-TL1 (80%), MT-TV)?
MELAS
Which disorder is caused by hypermethylation at Xq27.3?
Fragile X
Which disorder is caused by Hypermethylation of FMR1, which codes for FMRP?
Fragile X
Which disorder is caused by mutation in 15q21.1?
Marfan Syndrome
Which disorder is caused by mutation in 16p13.3 (85% of cases)?
Polycystic Kidney Disease
Which disorder is caused by mutation in 17q11.2?
Neurofibromatosis
Which disorder is caused by mutation in 19q13.3?
Myotonic Dystrophy Type 1
Which disorder is caused by mutation in 4p16.3?
Achondroplasia
Which disorder is caused by mutation in 4p16.3?
Huntington’s Disease
Which disorder is caused by mutation in 4q22.1 (15% of cases)?
Polycystic Kidney Disease
Which disorder is caused by mutation in 7q21.3?
Osteogenesis Imperfecta 1
Which disorder is caused by mutation in COL1A1?
Osteogenesis Imperfecta 1
Which disorder is caused by mutation in DMD at Xp21-21.1?
Muscular Dystrophy
Which disorder is caused by mutation in DMPK?
Myotonic Dystrophy Type 1
Which disorder is caused by mutation in F8?
Hemophilia A
Which disorder is caused by mutation in FBN1?
Marfan Syndrome
Which disorder is caused by mutation in fibroblast Growth Factor Receptor 3 (FGFR3)?
Achondroplasia
Which disorder is caused by mutation in HTT
Huntington’s Disease
Which disorder is caused by mutation in LDLK, APOB, and PCSK9?
Familial Hypercholesterolemia
Which disorder is caused by mutation in MT-ND1, MT-ND, MT-ND4L, MT-ND6?
Leber Hereditary Optic Neuropathy
Which disorder is caused by mutation in MT-TK?
MERRF
Which disorder is caused by mutation in NF1 (neurofibromin) ?
Neurofibromatosis
Which disorder is caused by mutation in PHEX?
Hypophosphatemia
Which disorder is caused by mutation in Polycystin 1 and 2 (PKD1 and PKD2)?
Polycystic Kidney Disease
Which disorder is caused by mutation in RB1?
Retinoblastoma
Which disorder is caused by mutation in Xq28?
Hemophilia A
Which disorder is characterized by a disorder of ocular, skeletal and cardiovascular connective tissue, aortic root enlargement, Ectopia lentis, and a variety of other signs?
Marfan Syndrome
Which disorder is characterized by a malignant tumor of the retina?
Retinoblastoma
Which disorder is characterized by adult onset muscular dystrophy, progressive muscle wasting and weakening, myotonia, cataracts, and cardiac conduction defects?
Myotonic Dystrophy Type 1
Which disorder is characterized by bilateral renal cysts, cysts in other organs, vascular abnormalities, and end stage renal disease in 50% by age 60?
Polycystic Kidney Disease
Which disorder is characterized by café au lait spots, neurofibromas, plexiform neurofibroma, freckling in axillary or inguinal area, optic glioma, Lisch nodules, and osseus lesions?
Neurofibromatosis
Which disorder is characterized by high cholesterol and LDL levels, xanthomas, and premature coronary artery disease and death?
Familial Hypercholesterolemia
Which disorder is characterized by hypophosphatemia, short stature, and bone deformities?
Hypophosphatemia
Which disorder is characterized by intellectual disabilities (dysmorphic features: large ears, long face, macroorchidism), autistic behavior, social anxiety, hand-flapping/biting, and aggression?
Fragile X
Which disorder is characterized by loss of normal movement and coordination, loss of communication skills, failure to thrive, seizures, abnormal hand movements?
Rett Syndrome
Which disorder is characterized by multiple fractures, mild short stature, adult onset hearing loss, and blue sclera?
Osteogenesis Imperfecta 1
Which disorder is characterized by muscle symptoms, seizures, ataxia, dementia, ragged-red fibers?
MERRF
Which disorder is characterized by muscle weakness, seizures, repetitive stroke-like episodes, elevated lactic acidosis?
MELAS
Which disorder is characterized by neurological and behavioral abnormalities, overproduction of uric acid, self-injury?
Lesch-Nyhan Disease
Which disorder is characterized by o Eyes affected, cardiac conduction defects, ataxia, deafness, kidney problems?
Kearns-Sayre
Which disorder is characterized by progressive muscle weakness proximal to distal, calf hypertrophy, dilated cardiomyopathy, CK levels 10 times higher, onset before 15, wheelchair bound before 13, death in 30s?
Duchenne Muscular Dystrophy
Which disorder is characterized by progressive muscle weakness proximal to distal, calf hypertrophy, dilated cardiomyopathy, CK levels 5 times higher, onset later, wheelchair bound before 16, death in 40s?
Becker Muscular Dystropy
Which disorder is characterized by progressive neuronal degeneration causing motor, cognitive, and psychiatric disturbances that result in death~15 years after onset?
Huntington’s Disease
Which disorder is characterized by small stature (about four feet), rhizomelic limb shortening, short fingers, genu varum, trident hands, large head/frontal bossing, midfacial retrusion, small cranium magnum/craniocervical instability?
Achondroplasia
Which disorder is characterized by spontaneous bleeding into muscles, joints or intercranially, excessive bruising, prolonged bleeding after injury or excision, delayed wound healing?
Hemophilia A
Which disorder is characterized by vision loss (50% of males; 15% of females)?
Leber Hereditary Optic Neuropathy
Which disorder may be treated by cochlear implants?
Non-syndromic Deafness
Which disorder may be treated by treating complications and, more controversially, surgical limb lengthening and Growth Hormone therapy?
Achondroplasia
