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