Educational Immersion Experience Title: Genetic Regulation of Surfactant Deficiency
Mentor(s): F. Sessions Cole, M.D., and Aaron Hamvas, M.D.
Location: MPRB 5th floor
Educational goals:
1) Understand methodological issues related to sequencing and genotyping
2) Understand approaches for phenotyping of lung diseases
3) Understand informatics infrastructure necessary to manage large genotype and clinical data sets
4) Apply genetic epidemiologic strategies for univariate and regression analyses of genetic association
Weeks 1-3:
Participate in laboratory meeting (1 hour/week)
Genotype own DNA for SFTPB (PCR amplification, BigDye Terminator
sequencing), analyze with Phred, Phrap, and Consed (6 hours/week)
Meet with Drs. Hamvas and Cole (1 hour/week)
Weeks 3-6: Participate in laboratory meeting (1 hour/week)
Genotype own DNA ABCA3 (4 hours/week)
Seek informed consent for genetic research (2 hours/week)
Meet with Drs. Hamvas and Cole (1 hour/week)
Weeks 7-9: Participate in laboratory meeting (1 hour/week)
Analyze Missouri cohort SFTPB resequencing data (N=1,116) for evidence
of recombination hot spot (3 hours/week)
Analyze neonatal intensive care unit case (neonatal respiratory distress)control cohort (N=500) for associations between SFTPB and
ABCA3 genotypes and disease severity, using univariate and
regression analyses (3 hours/week)
Meet with Drs. Hamvas and Cole (1 hour/week)
Weeks 10-12: Participate in laboratory meeting (1 hour/week)
Analyze case-control cohort (N=500) for SFTPB-ABCA3 interactions (6
hours/week)
Present one hour seminar concerning association of candidate gene
variation and severity of neonatal respiratory distress (1
hour/week)
Meet with Drs. Hamvas and Cole (1 hour/week)
Suggested readings:
Hamvas, A., Madden K, Nogee LM, Trusgnich MA, Wegner DJ, Heins H, Cole F. S. (2004). Informed consent
for genetic research. Arch Pediatr Adolesc Med 158(6): 551-555
Whitsett, J. A., S. E. Wert, Y. Xu. (2005). Genetic disorders of surfactant homeostasis. Biol Neonate 87(4):
283-7.
Nogee, L. M. (2004). Alterations in SP-B and SP-C expression in neonatal lung disease. Annu Rev Physiol 66:
601-23.
Hamvas, A., Wegner, DJ, Trusgnich, MA, Madden, K, Heins, H, Liu, Y, Rice, T, An, P., Watkins-Torry, J., Cole,
FS (2005). Genetic variant characterization in intron 4 of the surfactant protein B gene. Hum Mutat 26(5):
494-5.
Carlson, C. S., M. A. Eberle, et al. (2004). Selecting a maximally informative set of single-nucleotide
polymorphisms for association analyses using linkage disequilibrium. Am J Hum Genet 74(1): 106-20.
Crawford, D. C., D. T. Akey, et al. (2005). The patterns of natural variation in human genes. Annu Rev
Genomics Hum Genet 6: 287-312.
Crawford, D. C., T. Bhangale, et al. (2004). Evidence for substantial fine-scale variation in recombination rates
across the human genome. Nat Genet 36(7): 700-6.
Myers, S., L. Bottolo, et al. (2005). A fine-scale map of recombination rates and hotspots across the human
genome. Science 310(5746): 321-4.
Przeworski, M. (2005). Genetics. Motivating hotspots. Science 310(5746): 247-8.
de Bakker, P. I., R. Yelensky, et al. (2005). Efficiency and power in genetic association studies. Nat Genet
37(11): 1217-23.