3. Developmental Genetics Flashcards
Define and discuss the basic classifications used in dysmorphology (objective)
Answer later
Discuss the basic principles of morphogenesisdevelopment (objective)
Answer later
Discuss broadly some of the clinical syndromes seen in human developmental biology, including the associated genes (objective)
Answer later
Congenital Anomalies (frequency)
Undescended testicles and heart defect most common
Cleft palate, craniosynostosis, syndactyly
Deformation
Unusual forces on normal tissue
Usually no inherent problem in the embryo/fetus/neonate
Mechanical forces result in altered morphogenesis, usually molding
Examples: uterine constraint, oligohydramnios, breech position, positional plagiocephaly
Recurrence risk is generally low
Disruption
Breakdown of normal tissue
Normal fetus subjected to destructive problem causing breakdown or loss of normal tissue
Causes: vascular, infection and mechanical problems
Example: amniotic band sequence (don’t need to karyotype)
Usually sporadic; but in large series there are more associated anomalies
Dysplasia
Abnormal organization of cells into tissue (seen microscopically)
Abnormal migration of cells
Not in use as widely currently
Malformation
Poor formation of tissue
A single localized abnormality in formation of tissue that initiates a chain of subsequent defects
Can be nearly normal or more severe
Can suggest a syndromic diagnosis
Many examples in JCB
Syndrome
A pattern of anomalies, at least one of which is morphologic, known or thought to be causally related
-A mutation in a key developmental gene may be associated with multiple malformations (called malformation syndrome)
Sequence
One or more secondary morphologic anomalies known or presumed to cascade from a single malformation, disruption, dysplasia, or deformation
Anomaly
An anatomic (microscopic and macroscopic) phenotype that represents a substantial departure from the appropriate reference population
Phenotypic Heterogeneity
Different mutations in a gene
Hypochondroplasia (H)
Thanatophoric dysplasia (T)
Achondroplasia (A)
Non-specificity of cleft lip/palate
Isolated cleft lip/palate
Vs.
Syndromic cleft lift/palate (EEC syn.)
Syndromic will see anomalies elsewhere as well
Syndromes related by Pathway
“Ras-opathies”
Different genes mutated in same pathway
All increase risk of cancer
Normal Developmental Processes (list)
Fundamental problem Proliferation Differentiation Migration Apoptosis Rac1
Fundamental Problem (development)
Turn a single cell (fertilized egg) into a fully and normally developed organism
Proliferation (development)
Increase cell number by division
Differentiation (development)
Formation of specialized cell types
Migration (development)
Cells move in characteristic patterns
Apoptosis
Cells die in the characteristic patterns
Rac1
Multiple roles in cellular functions, including actin cytoskeleton organization, cell adhesion, migration, proliferation, and apoptosis in mammalian cells
Probability
Inbred strains of mice, genetically identical
The same formin gene mutation causes renal aplasia in only 20% of the carriers of the mutation
What explains the difference in the occurrence in affected vs. unaffected?
Cell Proliferation
Needed for growth to occur
Excess cell reproduction causes abnormally large body structures, often with abnormal function
No karyotype needed, cell increase on one side
Ex. Hemihyperplasia
Human Tumors
Dysfunctional p53 proteins
Functional p53: tumor suppressor protein
Cell cycle clock, Cyclins, CDK
Inhibitory proteins like p53 induce cell death
