In-class questions (group)

Discuss these questions with members of your group, come to a consensus answer fro each question (you may incorporate several opinions/ideas into one answer), and hand in your group’s answers via email after class (ONE set of answers per group, please include the first names of all contributors). Please also send a copy to all contributors, and if you feel so inclined, please feel free to include this piece of work in your portfolio.

 

Part I – The study of limb phenotypes (10 min)

 

1. What big processes of development are involved in the formation of a human limb?

• Pattern formation, differential gene expression, timing

 

2. Think about human limb development (wild-type or mutant) as a phenotype of interest. From a fundamental research perspective, why is it a useful phenotype to study? Why is it a good model system for the study of development? What are the advantages?

• Easy to see and compare at early stages
• Expression mechanism can explain phenotype/genotype
• Developmental problem, possible solution for disorders/illnesses

 

3. What is the difference between an isolated and a syndromic malformation, and what kinds of mutations are they postulated to be associated with?

• Isolated malformation is a defect in a single system and can have many causes, while syndromic malformation is a pattern of anomalies that have a single cause (made some corrections from the group discussion).

 

 

Part II – The study of cis-regulatory elements (20 min)

 

4. Select one of the loci discussed in the review by Bhatia and Kleinjan. As a group, prepare a model of its regulation (can be in words, diagrams, a mixture thereof, etc). Then:
   • list the evidence that the authors use as a basis for each part of the model;
   • evaluate the evidence (decide if it is sufficient to support the various parts of the model);
   • if applicable, select a part of the model for which we do not (yet) have much supporting evidence. What additional piece(s) of evidence would help strengthen the model? What experiment(s) could you do to obtain them?

• ZRS enhancer controls Shh expression in developing limb bud
• single base pair substitutions or duplications that encompasses the ZRS region
• The point mutation results in a wrong 3D structure that affects level of  Shh expression. Ex. it regulates the Shh because it binds to other regulatory protein at higher affinity. The change in Shh causes the bud to express extera digits (at the phenotype – Cuban and Belgian mutation)

 

5. What is synteny? How does progress in our identification of cis-regulatory elements help explain some cases of synteny? (And thus making the connection between genome structure, function and evolution relevant?)

 

 

•  Synteny is the degree to which the patterns/orders of genes are similar in 2 compared genomes. Some Cis-resulatory regions have been conserved in evolution. Recent common ancestors will have more synteny between their chromosomes.

Part III – Where do the cases are from, and who is the information for? (10 min)

 

6. Think about all the research conducted on human limb malformation. How do you think the subjects for the study were recruited? How do you think the information gained from these studies was disseminated? Who had access to it? Who could it be useful or interesting for? How are the phenotypes under study depicted?

• Subjects could be recruited via
  • Volunteers
  • Direct request from researchers
  • Paid
  • Anonymous information from hospitals
  • Depending on the researchers doing the study it could be free access on the web, in journals, or sold in a journal. The researchers and medical institutions could all have access to the information. It could be interesting for physicians, other researchers working in the same area and other individuals with the genetic condition. The phenotypes under study are depicted as descriptions, pictures or experimental data.

 

OR: (please answers only one of Q6 or Q7, not both)

 

7. Understanding human “pathologies” that have a genetic basis is almost always listed as one of the benefits of uncovering the genetic and molecular mechanisms that cause a given phenotype. How does the knowledge obtained in this field benefit the patients/subjects? How does it benefit the community at large?