Developmental genetics
mechanisms and pathways responsible for normal human development in utero
Dysmorphology
a study of congenital birth defects that alter the shape or form of one or more parts of the body of a newborn child (Or a study of destruction or interruption of normal tissue)
Three major categories of birth defect:
Malformation
Deformation
Disruption
Malformation
from intrinsic abnormalities in one or more genetic programs operating in development, e.g., extra fingers due to mutations
disruption
result from destruction of irreplaceable normal fetal tissue (loss normal tissue)
Deformations
are caused by extrinsic factors that impact physically on fetus development, e.g., contractions of the joints
Pleiotropy
a single causative agent results in abnormalities
of more than
one organ systems
Syndrome Pleiotropy
causative agent (mutation or teratogen) causes multiple
abnormalities
in parallel, collection of abnormalities
Sequence Pleiotropy
a mutant affects only a single organ system at a
point in time, that causes rest
of related organs or tissue →
secondary effects
What is developmental genetics?
?mechanisms and pathways responsible for normal human development in utero
How many % of deaths were attributed to birth defects in the US?
6 deaths / 1000 live births (~0.6%)
What program(s) or clinics can help with early diagnosis and
decreasing infant
deaths?
Clinics of genetic counseling and prenatal diagnosis help with early diagnosis, therefore decreasing infant deaths
Developmental Genetics
An action of genes interacting with cellular and environmental factor; Developmental disorders are caused by chromosomal, sub-chromosomal or gene mutations
Probability
not only genes, but also other processes are regulators of development. Probability plays in normal development or a range of developmental outcomes (normal and abnormal).
Environmental Factors
in a cell or tissue play a central role in providing a normal developmental context. Unexpected environment agents (e.g., drugs, X-rays, or other agents) can be teratogens → interfere with molecules in the pathways
Four basic cellular processes
proliferate, differentiate, migrate and apoptosis
Cellular Growth Process
Four basic cellular processes (proliferate, differentiate, migrate
and apoptosis)
act in various combinations →allow growth and
morphogenesis → create an
embryo containing normal organs of
size, shape, and location, and consisting of
tissues and cells
with correct architecture, structure, and function
During development
cells divide (proliferate), acquire novel functions or structures (differentiate), move within the embryo (migrate), and undergo programmed cell death (often through apoptosis)
Fundamental Mechanisms in Development
1. Gene regulation by transcription factors
2. Cell-cell
signaling by direct contact and by morphogens
3. Induction of
cell shape and polarity
4. Cell movement
5. Programmed cell death
Cell-cell signaling
communication system consisting of cell surface receptor and a ligand
ex) insulin receptor and insulin
Ligand binding
receptors transmit their signals through intracellular signaling pathways
Induction of cell shape and polarity
Cells must organize themselves with respect to their position and polarity in their microenvironment
Induction of cell shape and polarity (IN DISEASE)
Cells fail to sense fluid flow or to activate or repress signal
transduction
pathways→ cells continue to proliferate and do not
undergo appropriate
polarization→ formation of cysts,
fluid-filled spaces lined by renal tubular cells
Cell movement and programmed cell death
#4. Cell movement is critical, such as cells in the central nervous
system (CNS)
#5. Programmed cell death (apoptosis): necessary for
morphological
development of many structures
Apoptosis
one major form of programmed cell deaths, which destroy
cells
that represent a threat to our body (e.g., tissue, cells)
For
example:
- cells infected with viruses
- cells with DNA
damage
- cancer cells (uncontrolled proliferated cells)
Necrosis v Apoptosis
necrosis - NOT programmed
apoptosis - programmed