Genomic convergence

Genomic convergence is a multifactor approach used in genetic research that combines different kinds of genetic data analysis to identify and prioritize susceptibility genes for a complex disease.

Early Applications

In January 2003, [http://wwwchg.duhs.duke.edu/faculty/mhauser.html Michael Hauser] along with fellow researchers at the [http://wwwchg.duhs.duke.edu Duke Center for Human Genetics (CHG)] coined the term “genomic convergence” to describe their endeavor to identify genes affecting the expression of Parkinson disease (PD). Their work successfully combined serial analysis of gene expression (SAGE) with genetic linkage analysis. The authors explain, “While both linkage and expression analyses are powerful on their own, the number of possible genes they present as candidates for PD or any complex disorder remains extremely large” [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12620972&query_hl=3&itool=pubmed_docsum(1)] . The convergence of the two methods allowed researchers to decrease the number of possible PD genes to consider for further study.

Their success prompted further use of the genomic convergence method at the [http://wwwchg.duhs.duke.edu CHG] , and in July 2003 [http://wwwchg.duhs.duke.edu/faculty/y-jli.html Yi-Ju Li] et al published a paper revealing that glutathione S-transferase omega-1 (GSTO1) modifies the age-at-onset (AAO) of Alzheimer disease (AD) and PD [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14570706&query_hl=5&itool=pubmed_docsum(2)] .

In May 2004, [http://www.mihg.org/weblog/people/2007/11/margaret-pericakvance-phd.html Dr. Margaret Pericak-Vance] , then the Director of the [http://wwwchg.duhs.duke.edu CHG] , articulated the value of the genomic convergence method at a [http://www.nyas.org/index.asp New York Academy of Sciences (NYAS)] keynote address entitled "Novel Methods in Genetic Exploration of Neurodegenerative Disease." She stated, "No single method is going to get us where we need to be with these complex traits. It is going to take a combination of methods to dissect the underlying etiology of these disorders" [http://www.nyas.org/ebriefreps/main.asp?intSubsectionID=1015 (3)] .

Recent and Future Applications

Genomic convergence has a countless number of creative applications that combine the strengths of different analyses and studies. Maher Noureddine et al, note in their 2005 paper, “One of the growing problems in the study of complex diseases is how to prioritize research and make sense of the immense amount of data now readily available at the click of a computer mouse...The best approach may be to take advantage of the strengths of both…SAGE …and microarrays” [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15966006&query_hl=7&itool=pubmed_docsum (4)] .

The results of combining methods of analysis have continued to be promising. Sofia Oliveira et al (2005) combined gene expression, linkage data, and “iterative association mapping” to identify several genes associated with PD AAO [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15986317&query_hl=9&itool=pubmed_docsum (5)] .

Future studies will continue to apply genomic convergence to elucidate the etiology of complex diseases. Dr. [http://www.mihg.org/weblog/people/2007/11/jeffery-m-vance-md-phd.html Jeff Vance] , Director of the [http://wwwchg.duhs.duke.edu/udall/ Morris K. Udall PD Research Center of Excellence] , notes, “Genomic convergence is really no different from mathematical convergence – the more angles from which you can come at a problem, the better chance you have of solving it” [http://www.genome.duke.edu/genomelife/glarchive/issue1/udall (6)] .

References

1. Hauser MA, Li Y-J, Takeuchi S, Walters R, Noureddine M, Maready M, Darden T, Hulette C, Martin E, Hauser E, Xu H, Schmechel D, Stenger JE, Dietrich F, Vance JM. Genomic Convergence: Identifying candidate genes for Parkinson disease by combining serial analysis of gene expression (SAGE) and genetic linkage. Human Molecular Genetics 12(6):671-676, 2003. [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12620972&query_hl=3&itool=pubmed_docsum PMID:12620972]

2. Li YJ, Oliveira SA, Xu P, Martin ER, Stenger JE, Hulette C, Scherzer CR, Hauser MA, Scott WK, Small GW, Nance MA, Watts RL, Hubble JP, Koller WC, Pahwa R, Stern MB, Hiner BC, Jankovic J, Goetz CG, Mastaglia F, Middleton LT, Roses AD, Saunders AM, Welsh-Bohmer KA, Schmechel DE, Gullans SR, Haines JL, Gilbert JR, Vance JM, and Pericak-Vance MA. Glutathione S-Transferase modifies age-at-onset of Alzheimer disease and Parkinson disease. Human Molecular Genetics 12 (24): 3259-67, 2003. [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14570706&query_hl=5&itool=pubmed_docsum PMID:14570706]

3. New York Academy of Sciences eBriefings: [http://www.nyas.org/ebriefreps/main.asp?intSubsectionID=1015 Genetic Exploration of Alzheimer's and Parkinson's Diseases]

4. Noureddine MA, Li, Y-J van der Walt JM, Walters R, Jewett RM, Xu H, Wang T, Walter J, Scott BL, Hulette C, Schmechel D, Stenger J, Dietrich F, Vance JM, and Hauser MA. Genomic Convergence to identify candidate genes for Parkinson disease: SAGE analysis of the Substantia nigra. Movement Disorders, Epub 2005. [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15966006&query_hl=7&itool=pubmed_docsum PMID: 15966006]

5. Oliveira S, Li Y, Noureddine M, Zuchner S, Qin X, Pericak Vance MA, Vance JM. Identification of risk and age-at-onset genes on chromosome 1p in Parkinson disease. American Journal of Human Genetics, 77(2):252-64, 2005. [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15986317&query_hl=9&itool=pubmed_docsum PMID: 15986317]

6. GenomeLife: [http://www.genome.duke.edu/genomelife/glarchive/issue1/udall Udall Centers Meeting Points Up Parkinson's Work at Duke]