Developmental Diseases Flashcards
What are the two main categories of factors that contribute to developmental diseases
-Genetic factors
-Environmental factors
-Can be combo of the two
What factor is the most likely cause of congenital developmental disease
Genetic
3 major categories of genetic factors
-Chromosomal abnormalities
-Single gene abnormalities
-Multifactor abnormalities
Chromosomal abnormalities
Most common one associated with severe morphological defects. Usually due to changes in number or structures of chromosomes
Monosomy
One less chromosome
Trisomy
Extra chromosome
Result of chromosome abnormalities
Often cause embryonic death, abortion, or still births
Single gene abnormalities
Changes in single protein. Depending on that protein can have little or no effect or sever effects
Major categories of genes affected in single gene abnormalities
-Structural proteins
-Receptor proteins
-Enzymes
-Regulatory proteins
Inheritance of single gene abnormalities
-Autosomal
-Sex linked
Multifactorial
Disease due to two or more gene abnormalities
Syndactyly
Fusion of two functional digits “mulefoot” Can happen in humans. Common in bovines (autosomal recessive in holsteins)
Where is the bovine syndactyly defect found
On bovine chromosome 15 containing Lrp4 gene. 2 aa subsitution
LRP4 gene
Negative regulator of the Wnt-B-catenin pathway causing abnormal limb development and sometimes craniofacial anomalies and other mutations
Cenani-Lenz syndrome
Human syndactyly because of LRP4 mutation
Environmental factors that affect embryogenesis
-Infection (especially viruses)
-Chemicals
-Nutrition
-Age fetus exposed is critical to nature of the defect
Common viruses that causes developmental abnormalities
-Bovine diarrhea virus
-Feline panleukopenia virus
-Bluetongue virus
Exposure to BVD before 100 days
Fetal death
Exposure to BVD 100-170
Cerebellar, cerebral and ocular lesions
Exposure to BVD after 170
Persistent infection and lymphoid atrophy
Fetal infection with bluetongue virus in sheep
Damages developing neurons and get hydranencephaly earlier in gestation. Later in gestation get porencephaly
Chemicals that cause develpomental problems
Time of infection is very important. Generally comes from plants
Veratrum californicum in sheep
At 14 days gestation: cyclopia and severe craniofacial defects
29 days: metacarpal and metatarsal shortening
31 days: tracheal and larungeal stenosis
Cyclopia in sheep
Severe manifestation of holoprosencephaly
Holoprosencephaly
Disorder from failure of the embryonic forebrain to subdivide properly can be likd or severe
What is veratrum californicum
Corn lily has cholesterol-like alkaloids
What is the function of cholesterol
-Structural components of cell membranes. High ratios means low permeability and high stability
-Precursor of steroid hormones and bile acids
Shh gene/ hedgehog genes
Codes for protein needed for normal nervous system development during embryogenesis. It is a transcriptional regulatory protein. Must be cleaved by cholesterol to become active
HH genes
Regulate cell proliferation and growth factors post-natally
Shh mechanism of action
Shh binds to patched after activation to allow smoothened to function. When bound to patched is bound to Shh it senses cholesterol and regulates the amount in the cell and smoothened induces transcription and allows cholesterol trafficking and cell differentiation
Veratrum and Shh
Binds to Shh but won’t activate so this inhibits it leading to reduction in cholesterol activities and cell differentiation
Nutrition on embryogenesis
Without proper nutrition you can get abnormal fetal development, whether it is from the mother not getting proper nutrition or uterine or placental abnormalities that prevent proper nutrition
Vitamin A on embryogenesis
Involved in signal transduction pathways associated with development. Need to develop eyes, CVS, hindbrain, lungs, and skeleton
Hypovitaminosis A
Brain and musculoskeletal abnormalities
Hypervitaminosis A
CNS, craniofacial anomalies, cardiac, musculoskeletal and thymic malformation
