Pediatric Dwarfisms Genetic Pearls of Skeletal Dysplasia Autosomal Dominant Achondroplasia FGFR-3 Inhibition of chondrocytes proliferation Apert Syndrome FGFR-2 Inhibition of chondrocytes proliferation CMT (80-90%) PMP22 Nerve demyelination Pseudoachondroplasia COMP Abnormal cartilage formation SED congenita COL2A1 / Type II collagen Defect in cartilage matrix formation Kniest's Syndrome Type II collagen Type II collagen MED - Type I COMP Type II collagen MED - Type II Type IX collagen Jansen's metaphyseal chondrodysplasia PTHrP Functional defect in parathyroid hormone Schmid's metaphyseal chondrodysplasia Type X Collagen Defect in cartilage matrix formation Cleidocranial dysplasia CBFA-1 Impaired intramembranous ossification Osteogenesis Imperfecta (Type I, IV) COL1A1/COL1A2 Type I collagen Autosomal Recessive Diastophic dysplasia DTD (Sulfate Transport Protein) Defect in sulfaction of proteoglycan Friedreich's Ataxia Frataxin Osteo. Imperfecta (Type II, III) COL1A1/COL1A2 Type I collagen McKusick metaphyseal Unknown X Linked Recessive SED tarda COL2A1 Type II collagen CMT (10-20%) connexin gene Nerve demyelination Epigenetics Overview epigenetic changes include inheritable genetic alteration (developmental or environmental cues) that do NOT involve DNA mutation DNA methylation, histone modification, nucleosome location, or noncoding RNA are components of epigenetics osteoarthritis is thought to have epigenetic mechanisms that influence the disease process Translocations Overview translocations allow expression of genes (oncogenes) that are usually not active. cytogenetic analysis allows for the detection of gene translocations by evaluating the size and number of chromosomes isolated from the cell nucleus. Examples present in up to 95% of sarcomas. Disease Translocation Gene Ewing's sarcoma t (11:22) Fusion protein (EWS-FLI1) Rhabdomyosarcoma t (2:13) Pax3-FKHR Myxoid liposarcoma t (12:16) TLS-CHOP Synovial sarcoma t (X:18) SYT-SSX1, 2, or 4 fusion protein Clear cell sarcoma t (12:22) Fusion protein EWS-ATF1 Chondrosarcoma (Myxoid Variant) t (9:22) Fusion protein EWS-CHN Tumor Suppressor Genes Definition inhibit cell proliferation therefore a mutation interfering with normal function causes leads to uncontrolled cell growth Examples retinoblastoma protein (pRB-1) acts as a regulator of gene expression recessive suppressor both alleles must be mutated to have uncontrolled growth Rb mutation in 100% of retinoblastomas 35% of osteosarcomas abnormal state is phosphorylated and unable to bind to DNA to regulate p53 normal protein prevents entrance into S-phase of cell cycle when DNA is damaged dominant suppressor single allele must be mutated to have uncontrolled growth mutation in this gene found in 50% of all tumors osteosarcoma (20-65%) chondrosarcoma Oncogenes Definition induce uncontrolled growth normal function causes leads to uncontrolled cell Examples FAK focal adhesion kinase) Erb-2 epidermal growth factor variant Tumor Antigens Definition tumor antigens are used in the diagnosis, monitoring of treatment response, and are being researched for treatment options as anti-cancer vaccines Examples carcinoembryonic antigen (CEA) colorectal carcinoma carbohydrate antigen 19-9 (CA-19-9) pancreatic cancer carbohydrate antigen 125 (CA-125) ovarian cancer cancer antigen 15-3 (CA-15-3) breast cancer alpha fetoprotein (AFP) can be seen in many cancers, but is most commonly seen in hepatocellular carcinomas Assays Western blot detects protein Southern blot detects DNA Northern blot detects RNA Southwestern blot detects DNA binding proteins RT-PCR reverse transcription PCR highly sensitive, detects low copy number of RNA reversed transcribed into complimentary DNA (cDNA) may be used together with Northern blot siRNA blocks translation of mRNA useful for loss-of-function experiment designs
QUESTIONS 1 of 7 1 2 3 4 5 6 7 Previous Next Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK (OBQ07.266) Which of the following chromosomal translocations is associated with osteosarcoma? Review Topic QID: 927 1 SYT-SSX1 7% (32/435) 2 CHOP-TLS 9% (41/435) 3 EWS-FLI1 11% (48/435) 4 FKHR-PAX3 8% (34/435) 5 no translocation associated 64% (279/435) ML 2 Select Answer to see Preferred Response PREFERRED RESPONSE 5 (OBQ12.165) DNA methylation, histone modification, nucleosome location, or noncoding RNA are hypothesized to contribute to the process whereby inheritable genetic alterations occur that do not involve DNA mutation. Which of the following terms best defines this process? Review Topic QID: 4525 1 Transgenes 7% (246/3633) 2 Epigenetics 61% (2209/3633) 3 Gene enhancers 7% (249/3633) 4 Gene promoters 7% (266/3633) 5 Transformation 17% (620/3633) ML 4 Select Answer to see Preferred Response PREFERRED RESPONSE 2 (OBQ07.82) What serum marker is most closely associated with colorectal carcinoma? Review Topic QID: 743 1 Carbohydrate antigen 125 14% (206/1436) 2 Carcinoembryonic antigen 77% (1105/1436) 3 Carbohydrate antigen 19-9 5% (75/1436) 4 Cancer Antigen 15-3 1% (14/1436) 5 Alpha fetoprotein 2% (33/1436) ML 2 Select Answer to see Preferred Response PREFERRED RESPONSE 2 (OBQ06.95) A mutation of the retinoblastoma gene RB-1 leads to the development of malignancies such as retinoblastoma and osteosarcoma. Which term best characterizes the RB-1 gene? Review Topic QID: 206 1 growth factor 0% (0/412) 2 retro-oncogene 1% (3/412) 3 proto-oncogene 17% (69/412) 4 oncogene 11% (45/412) 5 tumor suppressor 71% (294/412) ML 3 Select Answer to see Preferred Response PREFERRED RESPONSE 5 (OBQ04.268) Which of the following sarcomas is correctly paired with its most common translocation? Review Topic QID: 1373 1 Alveolar rhabdomyosarcoma: t(9;22) 19% (272/1421) 2 Synovial sarcoma: t(11;22) 7% (104/1421) 3 Ewing's sarcoma: t(12;16) 4% (51/1421) 4 Myxoid liposarcoma: t(X;18) 9% (132/1421) 5 Clear cell sarcoma t(12;22) 60% (856/1421) ML 3 Select Answer to see Preferred Response PREFERRED RESPONSE 5 (OBQ08.156) Which of the following laboratory tools is used to detect genetic translocations for prenatal screening? Review Topic QID: 542 1 Western blot analysis 5% (47/953) 2 Northern blot analysis 4% (36/953) 3 Enzyme linked immunosorbent assay (ELISA) 14% (131/953) 4 Cytogenetic analysis 75% (711/953) 5 Flow cytometry 3% (24/953) ML 2 Select Answer to see Preferred Response PREFERRED RESPONSE 4