Asynchronous Dev. Genetics

Question 1

describe malformations

Answer 1

• abnormality that arises because of a primary error in morphogenesis due to an abnormal developmental process
  
  • due to errors occurring in the initial formation of strcuture; a primary structural defect of an organ or part of an organ
• ex: congenital heart abnormalities, cleft lip,

Question 2

describe sequence

Answer 2

• sequence aka malformation sequence
  
  • cascade of effect resulting from a single primary malformation
    
    • multiple defects caused by primary problem
  • Pierre-Robin sequnce = head and facial abnormalities

Question 3

describe syndrome (aka malformation syndrome)

Answer 3

• pattern of features that known to have a unifying underlying cause
  
  • manifestations arise from several different points during morphogenesis
• example = Down syndrome
  
  • not all features need to be present to make diagnosis

Question 4

describe disruption

Answer 4

• due to destructino of a tissue or organ after it is formed
• results in an abnormal structure of a tissue or organ or as a result of external forces
• usually not a genetically controlled event
  
  • ex: amniotic band disruption, can lead to amputation

Question 5

describe deformations

Answer 5

• deformations might be thought of as a mechanical distortions by a physical force upon an otherwise normal structure
• occurs while tissue is forming
  
  • clubfoot is caused by lack of amniotic fluid
  • might be surgically corrected

Question 6

describe dysplasia

Answer 6

• an abnormality in a tissue structure caused by abnormal cellular organization
• ex: FGFR3 mutation (achondroplasia) which affects many aspects of skeletal structure

Question 7

describe association

Answer 7

• traits coincide more often than expected by chance
  
  • traits are seemingly unconnected
  • a single genetic cause is not known
• only a subset of conditions are needed to fit

Question 8

describe SHH

Answer 8

• involved in dorsal/ventral patterning
• SHH is expressed at different temporal periods during development to control different areas
• SHH also establishes the zone of polarizing activity
  
  • involved in limb patterning

Question 9

describe the pathway of SHH

Answer 9

• the normal function of PTCH is to inhibit SMO but when SHH is bound to PTCH, SMO is free to activate downstream signaling
• GLI protein and CREBBP interact and activate gene expression by binding regulatory sequence on the DNA

Question 10

describe function of HOX

Answer 10

• HOX genes pattern the anterior/posterior axis of the embryo
• In the limb bud, HOX gene expression is established as a result of the generation of a gradient of SHH protein that is produced by the Zone of Polarizing Activity (ZPA)

Question 11

HOX genes encode ______

Answer 11

HOX genes encode transcription factors

• Typically, these TFs must dimerize to bind to DNA
• May be homodimers
• May be heterodimers

Question 12

describe HOX genes during development

Answer 12

• HOX genes arranged in clusters (normal genes are not arranged in clusters)
• As a body segment (or body part) needs instruction to develop, the next HOX gene is expressed
  
  • sequential expression during development controls body part formation during development

Question 13

describe the function of FGFR3

Answer 13

• FGFR3 is a transmembrane receptor tyrosine kinase
• G380R mutation of FGFR3 causes unregulated activity
• Growth plate is prematurely converted to bone