Craniofacial anomalies and genetics

Question 1

What is the Outcomes of the Human Genome Project (HGP)?

Answer 1

• 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 information in databases, making it available for data analysis,
• Has begun to address the ethical, legal, and social issues (ELSI) that arise from the project.
• Has catalyzed the multibillion-dollar U.S. biotechnology industry and analyses of the data will continue for many years.

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•Potential medical benefits through gene testing, gene therapy and pharmacogenomics.

Question 2

What are some modes of Inheritance?

Answer 2

• In every cell in our bodies is the same number of chromosomes and the same genetic material
• Paired chromosomes (22) plus a pair of sex chromosomes
• Gene pairs at same locus (alleles)
• They might be the same (homozygous) or different (heterozygous)
• These determine the expression of a characteristic

Question 3

What are Homeobox genes?

Answer 3

• Homeotic “Master” genes
• Encoding for transcription factors
• Involved in patterning, induction, apoptosis
• Control of epithelial /mesenchymal interaction

Question 4

How do Homeobox genes work?

Answer 4

• Through the neural crest cells (NCC)
• Ectomesenchyme of first branchial arch derived from the NCC
• Migration directed by homeobox genes

Question 5

What is the Origin of facial mesenchyme?

Answer 5

neural crest

Question 6

What is the Morphogenetic Cascade?

Answer 6

The basic morphogenetic processes of initiation, segmentation, patterning, migration and differentiation are mediated via a series of extracellular signalling molecules in a cascade of cellular events

Question 7

What gene is involved in Treacher Collins Syndrome?

Answer 7

The TCOF1 gene at 5q32 provides instructions for making a protein called treacle. This protein is active during early embryonic development in structures that become bones and other tissues of the face, and it appears to play a critical role in the formation of these structures.

Question 8

What is involved in the initiation, developmental position (patterning) and morphodifferentiation of tooth buds?

Answer 8

MSX1 and MSX2

Question 9

Facts:

• One gene = one protein
• Many genes = one character
• One gene affecting different characters = Pleiotropy

Answer 9

Facts:

• One gene = one protein
• Many genes = one character
• One gene affecting different characters = Pleiotropy

Question 10

What are Qualitative and Quantitative traits?

Answer 10

• Qualitative traits (discrete)
  
  • e.g. ABO blood antigens
• Quantitative traits (continuous)
  
  • e.g. Height, weight or tooth size

Question 11

What can Single Genes be?

Answer 11

• Dominant, e.g. Osteogenesis imperfecta
• Recessive, e.g. Cystic fibrosis
• X-linked, e.g. Amelogenesis imperfecta

Question 12

What is Penetrance and Expressivity?

Answer 12

• Penetrance: probability that presence of disease genotype will cause disease
• Expressivity: Variation in the severity of expression of a particular gene

EG: Treacher Collins Syndrome - full penetrance / variable expressivity

Question 13

What are X-linked inheritance: recessive?

Answer 13

• X-linked recessives 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

Question 14

What are X-linked inheritance: dominant?

Answer 14

• 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 (oro-facial-digital)