Developmental Abnormalities Mechanisms Flashcards
Developmental Diseases
Normal development is a complex process
Most developmental disease we recognize morphologically are due to abnormal embryogenesis
Congenital - Manifested at birth
Some deveolopmental diseases are manifested later in life due to abnormal postnatal development
Acquired - Occur after birth
Developmental Disease:
Causes
- Two main categories of factors contribute to developmental diseases
- Genetic Factors
- Environmental Factors
- A combination of these factors influences the development of many developmental diseases
- The cause of approximately 65% of congenital developmental disease is never determined
- of those whose cause is determined
- 70% are genetic
- 30% are environmental
- of those whose cause is determined
Genetic Factors
- Genetic factors can be placed into 3 major categories
- chromosomal abnormalities
- Single Gene Abnormalities
- Multifactor Abnormalities
Genetic Factors:
Chromosomal Abnormalities
- Most common abnormality associated with severe morphological defects
- Abnormalities are mainly due to changes in chromosome number or structure
- change in number
- monosomy:
- the cell has one less chromosome
- Trisomy:
- The cell has one extra chromosome
- monosomy:
- Some chromosomal abberations can be transmitted through some, but not all cell lines during embryonic development
- mosaicism
- Changes in Chromosome structure
- breakage can result in loss or rearrangement of chormosomes
- can be deleted, inverted, or translocated
- Most of these defects result in embryonic death, abortion, or stillbirth
- breakage can result in loss or rearrangement of chormosomes
- change in number
Genetic Factors:
Single Genes
This is a BIG DEAL
- Single gene abnromalities result in changes in a single protein
- protein may be structurally altered or expression may be affected
- These are often manifested as a functional abnormality
- These are not commonly associated with severe morphological defects
- Major Categories of Genes affected
- Structural Proteins
- Receptor Proteins
- Enzymes
- Regulatory Proteins
- Inheritance can be autosomal or sex-linked
- Autosomal
- Dominant: appear in every generation with onset generally later in life
- Recessive: may not appear in every generation with onset generally early in life
- Sex-linked
- Mainly X-linked recessive: Transmitted by asymptomatic females to some male offspring
- Autosomal
Genetic Factors:
Multifactorial
Disease due to two or more gene abnormalities usually along with some environmental factors
Multifactorial contributions are common with many normal traits, as well as both developmental and non-developmental diseases
Syndactyly
Syn = one
Dactyly = digit
Condition in cattle characterized by fusion or nondivision of the two functional digits
“Mulefoot”
One of the most common deformities of the hand and feet in humans
Bovine Syndactyly
- First reported in 1951
- autosomal recessive trait
- Peak incidence occurred in 1970s
- Defect was mapped to Bovine chromosome 15 in 1996
- conserved with human chormosome 11 and mouse chormosome 2
- Decet was mapped to 3.5Mb critical interval of the chromosome in 2006
- Defect due to a mutation in the LRP4 gene
- a 2 base-pair substitution in exon 33
- Glycine replaced cysteine
- a 2 base-pair substitution in exon 33
- Incidence of this condition has decreased due to progeny and genetic testing
Environmental Factors
These include any external factor that can affect embryogenesis
Could be infection, chemical, nutrition
Environmental Factors:
Infection
Fetal infection by a wide variety of agents can cause developmental anomalies
Bovine virus diarrhea virus
Feline panleukopenia virus
Bluetonge virus (cattle and sheep)
The age of fetal exposure has a critical impact on the nature of hte defect
Environmental Factor:
Infection:
Bovine Virus Diarrhea Virus
Fetal infection has different effects at different ages of development
- Exposure before 100 days
- fetal death
- Exposure between 100 -170 days
- various anomalies including cerebellar, cerebral, and ocular lesions
- Exposure after 170 days
- persistant infections and lympoid atrophy
Environmental Factors:
Infection:
Bluetongue virus in sheep
Viral exposure during development of cerebral hemispheres damages developing neurons and results in ventricular/cerebral anomalies
- Exposure between 50-55 days
- hydranencephaly
- Exposure at 75 days gestation
- porencephaly
Porencephaly
Hydranencephaly
Environmental Factors:
Chemical
- Maternal exposure to many different chemicals can cause fetal anomalies
- These are most common in grazing animals exposed to toxic plants
- Pharmacological agents and industrial chemicals can induce anomalies
- The nature of the defect is highly dependent on the time of exposure during gestation
