Updated: 8/23/2019

Genetic Pearls

Topic
Review Topic
0
0
Questions
7
0
0
Evidence
5
0
0
https://upload.orthobullets.com/topic/9025/images/directions.jpg
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
    • small interfering RNA; blocks translation of mRNA 
    • useful for loss-of-function experiment designs
 
 

Please rate topic.

Average 3.7 of 31 Ratings

Thank you for rating! Please vote below and help us build the most advanced adaptive learning platform in medicine

The complexity of this topic is appropriate for?
How important is this topic for board examinations?
How important is this topic for clinical practice?
Questions (7)
Question locked
Sorry, this question is for
PEAK Premium Subscribers only
Upgrade to PEAK

You have 100% on this question.
Just skip this one for now.

(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
Type in at least one full word to see suggestions list
1

Transgenes

7%

(250/3725)

2

Epigenetics

61%

(2273/3725)

3

Gene enhancers

7%

(254/3725)

4

Gene promoters

7%

(275/3725)

5

Transformation

17%

(629/3725)

L 4

Select Answer to see Preferred Response

SUBMIT RESPONSE 2

You have 100% on this question.
Just skip this one for now.

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

QID: 542
Type in at least one full word to see suggestions list
1

Western blot analysis

5%

(49/1006)

2

Northern blot analysis

4%

(38/1006)

3

Enzyme linked immunosorbent assay (ELISA)

14%

(138/1006)

4

Cytogenetic analysis

75%

(753/1006)

5

Flow cytometry

2%

(24/1006)

L 2

Select Answer to see Preferred Response

SUBMIT RESPONSE 4

You have 100% on this question.
Just skip this one for now.

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

QID: 927
Type in at least one full word to see suggestions list
1

SYT-SSX1

8%

(40/476)

2

CHOP-TLS

9%

(42/476)

3

EWS-FLI1

11%

(50/476)

4

FKHR-PAX3

7%

(34/476)

5

no translocation associated

65%

(309/476)

L 2

Select Answer to see Preferred Response

SUBMIT RESPONSE 5

You have 100% on this question.
Just skip this one for now.

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

QID: 743
Type in at least one full word to see suggestions list
1

Carbohydrate antigen 125

14%

(208/1462)

2

Carcinoembryonic antigen

77%

(1127/1462)

3

Carbohydrate antigen 19-9

5%

(76/1462)

4

Cancer Antigen 15-3

1%

(14/1462)

5

Alpha fetoprotein

2%

(34/1462)

L 2

Select Answer to see Preferred Response

SUBMIT RESPONSE 2

You have 100% on this question.
Just skip this one for now.

(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
Type in at least one full word to see suggestions list
1

growth factor

0%

(2/458)

2

retro-oncogene

1%

(3/458)

3

proto-oncogene

17%

(76/458)

4

oncogene

11%

(51/458)

5

tumor suppressor

71%

(324/458)

L 3

Select Answer to see Preferred Response

SUBMIT RESPONSE 5

You have 100% on this question.
Just skip this one for now.

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

QID: 1373
Type in at least one full word to see suggestions list
1

Alveolar rhabdomyosarcoma: t(9;22)

19%

(277/1459)

2

Synovial sarcoma: t(11;22)

7%

(107/1459)

3

Ewing's sarcoma: t(12;16)

3%

(51/1459)

4

Myxoid liposarcoma: t(X;18)

9%

(136/1459)

5

Clear cell sarcoma t(12;22)

60%

(882/1459)

L 3

Select Answer to see Preferred Response

SUBMIT RESPONSE 5
ARTICLES (9)
Topic COMMENTS (16)
Private Note