Zen and Colleen to present @ the upcoming Student Seminar: 11.20.08

Student Seminar is coming up again on Thursday, November 20th in 2289 CBRB @ noon.  Zen and Colleen will be presenting their latest and greatest research.  Keeping up with the tradition of the last couple of seminars, I’ve asked Zen and Colleen to provide some background information that will be useful for their talks.  See you Thursday.  

Zen Abrera-Abeleda’s Talk

The Role of the Alternative Pathway of the Complement System in the Development of Membranoproliferative Glomerulonephritis Type 2 or Dense Deposit Disease


Membranoproliferative glomerulonephritis 2 (MPGN2) or Dense Deposit disease (DDD; OMIMWikipedia) is a complex and rare disease affecting children and leading to end stage renal disease. It has been associated with the alternative pathway of the complement system. Our hypothesis is that the pathophysiologic basis of the development of MPGN2/DDD is due to the uncontrolled activation of the complement cascade leading to damage of host tissues. The goals for this project are to understand the role of the components of the alternative pathway of the complement system in the development of MPGN2/DDD by identifying allele variants, evaluating gene expression levels and determining changes in the activity and function of specific complement proteins. The long-term goal is to develop an effective treatment for MPGN2/DDD patients.

erik’s note: Zen has published on this topic twice.  

Abrera-Abeleda, M. A., Xu, Y., Pickering, M. C., Smith, R. J., and Sethi, S. (2007). Mesangial immune complex glomerulonephritis due to complement factor D deficiency. Kidney Int 71, 1142-1147. (Link)

Abrera-Abeleda, M. A., Nishimura, C., Smith, J. L., Sethi, S., McRae, J. L., Murphy, B. F., Silvestri, G., Skerka, C., Jozsi, M., Zipfel, P. F., et al. (2006). Variations in the complement regulatory genes factor H (CFH) and factor H related 5 (CFHR5) are associated with membranoproliferative glomerulonephritis type II (dense deposit disease). J Med Genet 43, 582-589. (Link)


Colleen Campbell’s Talk

Mapping of a novel Ménière’s disease locus to chromosome 1q32.1-q32.3
C.A. Campbell1,2, J. Webster3, C. Li4, D.A. Stephan3, R.J.H. Smith1,2.

1) Otolaryngology, University of Iowa, Iowa City, IA; 2) Interdepartmental PhD Program in Genetics, University of Iowa, Iowa City, IA; 3) Neurogenomics Division, Translational Genomics Research Institute, Phoenix, AZ; 4) Dept of Biostatistics, Harvard School of Public Health, Boston, MA.

Ménière’s disease (MD; OMIM; Wikipedia) is a complex disorder of unknown etiolog characterized by vertigcolleen_campbell2o, sensorineural hearing loss and tinnitus. Its reported incidence in Caucasians is 1-2 per 10,000(Morrison 1995), but most cases of MD are sporadic and only occasional families are identified with multiple affected persons (Oliveira 1992). The dearth of such families and the reduced penetrance of MD make classic linkage analysis difficult.

We identified a Chilean family segregating autosomal dominant MD over three generations and completed a genome-wide linkage scan using the Affymetrix GeneChip® Mapping 50K array. Five family members had definite MD, one individual had possible MD, 5 individuals were unaffected, and 4 individuals were too young to classify. Multi-point parametric linkage analysis assuming dominant inheritance and using DNA-Chip Analyzer software (dChip) (www.dchip.org) identified probable linkage to chromosome 1q32.1-q32.3 with a maximum LOD score of 2.36. The candidate gene interval determined by haplotype reconstruction spans 8.3 Mb (201.71- 210.29cM) and includes 79 known genes. No deafness locus maps to this region. The next linkage peak greater than 1 in this family was a LOD score of 1.66 at 17p12. This region spans 382 kb (12.65 – 13.03cM) and includes 6 genes.

Our study is significant because it identifies a locus for MD on 1q32. Since the phenotypes associated with sporadic and familial MD are indistinguishable, the identification of the causative gene in this family may have relevance to the definitive diagnosis of MD in sporadic causes. Furthermore, since little is known about MD and its initiating factors, the identification of a genetic contribution to this disease may help to clarify disease pathogenesis and possibly lead to better therapies.

erik’s note: Colleen has published four times on hearing-related genetics.

Hildebrand, M. S., de Silva, M. G., Klockars, T., Campbell, C. A., Smith, R. J., and Dahl, H. H. (2007). Gene expression profiling analysis of the inner ear. Hear Res 225, 1-10. Link

Vore, A. P., Chang, E. H., Hoppe, J. E., Butler, M. G., Forrester, S., Schneider, M. C., Smith, L. L., Burke, D. W., Campbell, C. A., and Smith, R. J. (2005). Deletion of and novel missense mutation in POU3F4 in 2 families segregating X-linked nonsyndromic deafness. Arch Otolaryngol Head Neck Surg 131, 1057-1063. Link

Chen, W., Campbell, C. A., Green, G. E., Van Den Bogaert, K., Komodikis, C., Manolidis, L. S., Aconomou, E., Kyamides, Y., Christodoulou, K., Faghel, C., et al. (2002). Linkage of otosclerosis to a third locus (OTSC3) on human chromosome 6p21.3-22.3. J Med Genet 39, 473-477.  Link

Campbell, C., Cucci, R. A., Prasad, S., Green, G. E., Edeal, J. B., Galer, C. E., Karniski, L. P., Sheffield, V. C., and Smith, R. J. (2001). Pendred syndrome, DFNB4, and PDS/SLC26A4 identification of eight novel mutations and possible genotype-phenotype correlations. Hum Mutat 17, 403-411.  Link


Posted on November 18, 2008, in Student Seminar and tagged , , , . Bookmark the permalink. Leave a comment.

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