Genetic Diseases in Craniofacial Morphology and Dysmorphology Flashcards
What are the outcomes of the Human Genome Project (HGP)?
- Identified all the approximately 20,000-25,000 genes in human DNA and the sequences of the 3 billion chemical base pairs that make up human DNA
- Stored this info in databases, making it available for data analysis
- Has begun to address the ethical, legal and social issues that arise from the project
- Has catalyzed the multibillion-dollar U.S. biotechnology industry and analyses of the data will continue for many years.
- Potential medical benefits through gene testing, gene therapy and pharmacogenomics.
What is Homeobox genes?
- Homeotic “master” genes
- encoding for transcription factors
- involved in patterning, induction, apoptosis
- Control of epithelial/mesenchymal interaction
How does Homeobox genes work?
- Through the neural crest cells (NCC)
- Ectomesenchyme of first branchial arch derived from NCC
- Migration directed by homeobox genes
What is the origin of facial mesenchyme?
Neural crest
What is the Morphogenetic Cascade?
The basic morphogenetic processes of initiation, segmentation, patterning, migration and differentiation are mediated via a series of extracellular signalling milecules in a cascade of cellular events
What is the homeobox genes and tooth development?
MSX1 and MSX2 in the initiation developmental position (patterning) and morphodifferentiation of tooth buds
Info expressed thorugh mesenchymal growth factors (FGF, EGF, TGFs and BMPs)
What does one gene, many genes and one gene affecting different charaters mean?
One gene = one protein
Many genes = one character
One gene affecting different charaters mean = Pleiotropy
What does Penetrance and Expressitivity mean?
Penetrance: probability that presence of disease genotype will cause disease
Expressitivity: Variation in the severity of expression of a particular gene
What is X-linked inheritance recessive?
- more common
- only males affected - females are carriers
- affected males may not survive or lack reproductive fitness
- female carrier transmits allele to half her sons and half daughters will be carriers
- male can transmit to daughters but not to sons
What happens in X-linked inheritance?
- Heterozygous female may show features of the condition
- due to non-random X-inactivation
- if X-chromosome with mutant allele remains active in some cells (disease)
- In those with normal allele - no disease manifestation
What is X-linked inheritance dominant?
- Acts like AD in that 50% males and 50% females will be affected
- more likely to be lethal in hemizygous males
- Females also affected (not just carriers)
- Rare - one craniofacial example being OFD syndrome