Genetics of development Flashcards
When the zygote divides into 16 cells, what does it then become?
Morula
What does the morula turn into?
Blastocyst
What two layers of cells does the blastocyst form?
Epiblast and hypoblast cells
Which layer of cells develops into the embryo?
Epiblast cells
What are the three layers of cells derived from epiblast cells?
Ectoderm, mesoderm, endoderm
what is the first axis of the embryo?
primitive streak
When can cells of the developing embryo be mutated and have the remaining cells compensate for it?
Regulative phase (up until primitive groove formation I think)
What is the phase of development after the regulative phase?
Mosaic phase
What are the three axes that are defined in the developing embryo?
crainial-caudal
dorsal ventral
left-right
What is the first axis to be developed in the embryo? What is it defined by?
anterior/posterior
primitive streak
Where do ectodermal cells invade into the space between the epiblast and hypoblast cells?
primitive streak
Where is the node of the primitive streak?
At the anterior end
What are the proteins that are secreted to specify the cranial/caudal ends?
noggin and chordin
What is the protein that causes the left/right axis to develop due to its unequal secretion at either end?
Sonic Hedgehog
Where is the sonic hedgehog protein produced from?
notocord
What protein is secreted from the left side of the notocord and is responsible for development of that side?
nodal
A defect in the right/left axis development that leads to the inversion of all of the internal organs is called what?
situs inversus
What is situs ambiguus?
Random dispersal of internal organs
In the axis of the embryonic limb the thumb to the fifth finger is designated what?
Anterior/posterior
What is the process of patterning?
The process by which the developing embryo divides up what part of the developing cell mass become thorax, abdomen, head etc.
Patterning along the anterior/posterior axis is determined by what genes?
the homeobox genes (HOX)
How does HOX determine the anterior/posterior axis?
different ratio of expression at different sites
What are the 5 cellular mechanisms operating in development?
- Gene regulation by transcription factors/chromatin modification
- Cell-cell signalling
- development of specific cell shape and polarity
- movement and migration of cells
- programmed cell death
What are malformations?
Problems with development that result from an intrinsic abnormality in the development process
Originate from the organ itself
What are deformations?
Problems with development that result from an extrinsic influence on the development of the affected tissue
Do no originate from the organ itself
What is oligohydraminos?
Lack of amniotic fluid during development?
What are disruptions?
Problems with development that result from the destruction of developing tissue
What are isolated anomalies?
anomalies that affect a single body region.
What is a sequence in the context of birth defects?
It is a cascade of events that starts from an isolated anomaly, and leads to multiple malformations (phenotype)
What are syndromes?
Phenotypes that affect several body regions; disease phenotype caused by a single defect simultaneously
How are anomalies classified?
By the time at which they occur in development
What are the most severe anomalies?
when they occur within the first 1-4 weeks of development
What is the VACTERL association?
Vertebral, Anal atresia, Cardiac, Tracheo-Esophagal fistula, Renal/Radial defects, Limb defects
What is the major risk factor for VACTERL?
Mother DM
How do abnormalities occurring from week 5-8 present?
Specific organs affected, with single major abnormalities (congenital heart defects)
How do abnormalities occurring after week 9 present?
mild effects
How are MAJOR anomalies defined?
Anything the requires surgery or major cosmetic consequences
How are MINOR anomalies defined?
Have little impact on the well-being of the patient.
What percentage of children are born with genetic birth defects in the U.S.?
2-3%
What percentage of infant mortalities are due to birth defects? Prematurity?
20%, 20%
What are the five most common birth defects?
Heart defects (1/100-1/200) Pyloric stenosis (1/300) Neural tube defects (1/1000) Orofacial clefts (1/700-1/1000) Clubfoot (1/1000)
What percentage of genetic defects have a complex inheritance? chromosomal defects? single gene mutations?
50% for complex
25% for chromosomal
20% for single gene
5% for nongenetic factors
