Human Disease Glycomics/Proteome Initiative (HGPI)
Overview of Project
Sugar chains are present in all cell membranes and encode important information beyond/behind the genome. Glycosyltransferases, about which there are approximately 300 known human genes (glycogenes), play a key role in the glycosylation process. Although the function of glycans on glycoproteins still remains elusive, there are emerging amounts of evidences accumulated in transgenic and knock-out mice regarding aberrant glycosylation which affects biological functions or leads to dysfunction.
The aim of this Initiative is to perform disease-related glycomics using
two complementary approaches - functional glycomics and high-sensitivity,
high-throughput mass spectrometry.
Overall, our plan is to identify disease-related glycosylation changes in blood and urine that represent potentially useful glycobiomarkers for the early diagnosis, monitoring and treatment of common disease such as cancer, inflammation, life style related diseases, neurodegenerative disease, and congenital disorder of glycosylation (CDG). In the process, we will also establish a common database platform and develop links with several other HUPO Initiatives. To this end, pilot studies on standard glycoprotein analyses as well as CDG screening were started in early 2005 at the Osaka Medical Center for Maternal and Child Health.
Structural analysis of N-glycans from the standard glycoproteins.?The purpose
is to develop a common data and analytical standard method of N-glycans
for various diseases.
Standard glycoprotein samples (transferrin and IgG) were prepared from sera of 4 different Japanese healthy volunteers.
- Human serum transferrin (total approx. 100 mg)
A,B,C.D (non-pooled sample)
- Human serum Immunoglobulin G (total approx. 100mg)
A,B,C.D (non-pooled sample)
The pilot project started in October, 2004 and the data was collected and analyzed by May, 2005 (please see Timetable and Protocols for the Pilot Study for details). July 31, 2005, at the Senri Hankyu Hotel, in Japan, the HCPI Steering Committee for the Pilot Study met to discuss the results. Their results will be presented at the 4th Annual HUPO Congress.
Diagnostic Program for Congenital Disorders of Glycosylation, CDG
Defects in the genes participating in the N-linked glycosylation pathway cause congenital disorders of glycosylation (CDG). CDG is divided into two groups, CDG-I and CDG-II; CDG-I is caused by altered synthesis and transfer of the dolichyl pyrophosphate-linked precursor oligosaccharide to recipient proteins, while CDG-II results from defects in the subsequent processing steps, mostly on N-linked sugar chains. At the end of 2004, 18 different types of CDGs were known and the responsible genes and their defects have been elucidated. However, we suspect that a number of different types and patients remain undiagnosed. A diagnosis is confirmed by molecular analyses which define abnormalities in the glycan moiety of glycoroteins. A diagnostic program, a leading project, has been launched in Japan and is anticipated to reveal the prevalence of this syndrome and promote understanding of the roles of glycans in glycoproteins or other glycoconjugates.
For details on participants and protocols, please see Diagnostic Program for CDG
Collaborations with other Initiatives
Bioinformatics and data-related issues are being coordinated with the Proteomics
NIH Consortium for Functional Glycomics
The Japanese Consortium for Glycobiology and Glycotechnology
Key Documents Related to Activities
The results of the pilot studies were presented in the HUPO Congress in Munich (August, 2005) and were published.
- 2010 Report to the HUPO Council from the HGPI
- Sep 27, 2009 Report to HUPO Board of Directors
- HGPI committee report August 2009
- JHUPO: http://www1.biz.biglobe.ne.jp/~jhupo/index-e.htm
- Pilot Studies: http://www.hgpi.jp/menuD.html
- Agenda for Initiatives Workshop August 27, 2005