Updated: 5/4/2022

Genetic Pearls

0%
Topic
Review Topic
0
0
0%
0%
Flashcards
21
N/A
N/A
Questions
9
0
0
0%
0%
Evidence
9
0
0
Topic
Images
https://upload.orthobullets.com/topic/9025/images/directions.jpg
  • Genetic conditions
      • Autosomal Dominant
      • Achondroplasia
      • FGFR3
      • Inhibition of chondrocytes proliferation
      • Apert Syndrome
      • FGFR2
      • 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 Dysplasia
      • COL2A1 / Type II collagen
      • Defect in cartilage matrix formation
      • MED - Type I
      • COMP
      • Type II collagen
      • MED - Type II
      • Type IX collagen
      • 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
      • RUNX2/CBFA1
      • Impaired intramembranous ossification
      • Osteogenesis Imperfecta
      • (Type I, II, III, IV, V)
      • COL1A1/COL1A2
      • Type I collagen
      • Autosomal Recessive 
      • Diastophic dysplasia
      • DTD
      • (Sulfate Transport Protein)
      • Defect in sulfaction of proteoglycan
      • Friedreich Ataxia
      • Frataxin
      • Osteogenesis Imperfecta
      • (Type VI)
      • SERPINF1
      • McKusick metaphyseal
      • RMRP gene
      • X-Linked Recessive
      • SED tarda
      • TRAPPC2 gene
      • 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.
        • Translocations
        • 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
          • Li-Fraumeni syndrome
  • 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
      • small interfering RNA; blocks translation of mRNA
      • useful for loss-of-function experiment designs

Please rate this review topic.

You have never rated this topic.

Thank you. You can rate this topic again in 12 months.

Flashcards (21)
Cards
1 of 21
Questions (9)
Question locked
Sorry, this question is for
PEAK Premium Subscribers only
Upgrade to PEAK
Question locked
Sorry, this question is for
PEAK Premium Subscribers only
Upgrade to PEAK
Question locked
Sorry, this question is for
PEAK Premium Subscribers only
Upgrade to PEAK

(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?

QID: 4525
1

Transgenes

7%

(282/4320)

2

Epigenetics

63%

(2725/4320)

3

Gene enhancers

7%

(284/4320)

4

Gene promoters

7%

(298/4320)

5

Transformation

16%

(680/4320)

L 4 D

Select Answer to see Preferred Response

(OBQ08.156) Which of the following laboratory tools is used to detect genetic translocations for prenatal screening?

QID: 542
1

Western blot analysis

5%

(69/1354)

2

Northern blot analysis

4%

(48/1354)

3

Enzyme linked immunosorbent assay (ELISA)

13%

(173/1354)

4

Cytogenetic analysis

75%

(1017/1354)

5

Flow cytometry

3%

(42/1354)

L 2 D

Select Answer to see Preferred Response

(OBQ07.266) Which of the following chromosomal translocations is associated with osteosarcoma?

QID: 927
1

SYT-SSX1

9%

(69/740)

2

CHOP-TLS

9%

(64/740)

3

EWS-FLI1

11%

(80/740)

4

FKHR-PAX3

7%

(54/740)

5

no translocation associated

64%

(471/740)

L 2 D

Select Answer to see Preferred Response

(OBQ07.82) What serum marker is most closely associated with colorectal carcinoma?

QID: 743
1

Carbohydrate antigen 125

14%

(230/1699)

2

Carcinoembryonic antigen

78%

(1317/1699)

3

Carbohydrate antigen 19-9

5%

(86/1699)

4

Cancer Antigen 15-3

1%

(18/1699)

5

Alpha fetoprotein

3%

(44/1699)

L 2 D

Select Answer to see Preferred Response

(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?

QID: 206
1

growth factor

0%

(3/761)

2

retro-oncogene

1%

(7/761)

3

proto-oncogene

17%

(130/761)

4

oncogene

11%

(81/761)

5

tumor suppressor

71%

(537/761)

L 1 D

Select Answer to see Preferred Response

(OBQ04.268) Which of the following sarcomas is correctly paired with its most common translocation?

QID: 1373
1

Alveolar rhabdomyosarcoma: t(9;22)

18%

(340/1877)

2

Synovial sarcoma: t(11;22)

7%

(140/1877)

3

Ewing's sarcoma: t(12;16)

5%

(103/1877)

4

Myxoid liposarcoma: t(X;18)

10%

(187/1877)

5

Clear cell sarcoma t(12;22)

58%

(1096/1877)

L 3 D

Select Answer to see Preferred Response

Evidence (9)
VIDEOS & PODCASTS (1)
EXPERT COMMENTS (18)
Private Note