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Building global networks for human diseases: genes and populations

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    This years Days of Molecular Medicinemeeting, organized by the Institute ofMolecular Medicine of the University ofCalifornia, San Diego, in collaboration withNature Medicine and the Wellcome Trust, wasthe first meeting in this series to be held out-side the United States. The venue was theSanger Centre (Hinxton, UK) and the topic ofthe meeting was Integrative Physiology andHuman Disease: Neurohormonal andMetabolic Pathways. Embedded in the vari-ous scientific sessions was a forum onBuilding Global Networks for HumanDiseases: Genes and Populations. The aim ofthis forum was to look at different examplesof national networks for the genetic study ofhuman disease and at the potential for futurecollaborations between scientists in NorthAmerica and Europe with science communi-ties elsewhere, particularly in developing andrestructuring countries.

    One of the most important challenges offuture biomedical research will be to dissectthe interplay between genetic makeup andenvironmental influences on the pattern ofdiseases worldwide1,2. With the humangenome available, it will be essential to iden-tify disease genes as a prerequisite to design-ing adequate diagnostic tools, drugs andvaccines for therapeutic interventions. In thisprocess, biobanksdepositories of vast num-bers of DNA samples, together with data on

    the health history of the donorshave a cru-cial role. But to be successful and provide use-ful information on the genetic factorsassociated with disease and their interactionwith environmental factors, an ideal biobankmust fulfill several requirements. It should berepresentative of the population and ideallyshould contain samples and data from at least500,000 subjects. There should be a goodintegration of clinical data over a long timeperiod and, preferably, linked multigenera-tional information. And the results thatemerge from its analysis must be susceptibleto validation, a process that requires access todata from other populations of differentgenetic background.

    Many countries either have already set upbiobanks or are about to do so. The UKBiobank (see Table 1 for a listing of biobanksand websites), a project jointly funded by theMedical Research Council (MRC), theWellcome Trust and the Department ofHealth, will include data on 500,000 peoplewhen fully established. In Canada, theCARTaGENE project will include informa-tion on 60,000 people. A European project,GenomEUtwin, will incorporate data on600,000 pairs of twins by coordinating exist-ing national twin registries, of which thelargest is the Swedish Twin Registry at theKarolinska Institutet, with data from 80,000pairs of twins.

    But in spite of their seemingly overwhelm-ing size, greater networking between thesenational initiatives could only further benefitour understanding of the most commoncauses of morbidity and mortality. Countriesof the developing and restructuring worldhave a great deal to offer in this context, as was

    highlighted by many examples presented atthe forum.

    George Chandy, director of the ChristianMedical College (Vellore, India), and QuasimMehdi, director general of the Biomedical andGenetic Engineering Laboratory (Islamabad,Pakistan), gave an overview of the researchportfolios of their institutions. In both coun-tries there are unique opportunities for col-laboration with research communitiesworldwide. Both nations have uniqueresources at their disposal. India and Pakistanare homes to a wide variety of ethnic groupswith specific patterns of disease. In addition,consanguineous marriages are very commonin both countries. This cultural feature has ledto a clustering of congenital diseases, whichcan be followed by establishing family trees.Good medical records going back many yearsare available, and in India they are often inEnglish. These assets could prove to be a goldmine when brought together with the latesttechnological platforms that are available tocountries with greater financial resources. Inboth India and Pakistan, research programsinvolving population-based studies arealready underway. Despite all these efforts,however, there is still a needwhich wasclearly expressed at the meetingto attractexternal funding and establish internationalcollaborations with scientists from developedcountries.

    There are other areas of research where col-laborations between the scientific communi-ties of the developing and the more developedworld would be mutually beneficial. Diseasepatterns in the western world have shiftedmarkedly over the past decades from infec-tious to noncommunicable diseases, and this

    Building global networks for humandiseases: genes and populationsHans-E Hagen & Jan Carlstedt-Duke

    Biobanks will have a crucial role in the identification of genes associated with disease a prerequisite to designingadequate diagnostic and therapeutic tools. To maximize their impact and chances of success, collaboration at aglobal scale is highly desirable.

    Hans-E Hagen is at the International Biomedical

    Programme, The Wellcome Trust, London, UK, and

    Jan Carlstedt-Duke is at the Karolinska Institutet,

    Stockholm, Sweden.



    2004 Nature Pu






    phenomenon is increasingly observed inother parts of the world, including India andPakistan. This could offer a prime opportu-nity to investigate the mechanisms underly-ing the association of changes in life style withshifts in health patterns, such as the growingproblems with obesity, diabetes and atopicdiseases (for example, asthma), especially inchildren. Both India and Pakistan have goodscientific infrastructure, with excellentnational research centers that could becomeinvolved in research of this sort.

    Another biobank presented at the forumwas the Estonian Genome Project, a brain-child of Andres Metspalu of the University ofTartu. A pilot project, which has been wellreceived by the Estonian public, is collectingthousands of blood samples as well as themedical histories of the donors, aiming even-tually to collect the DNA samples and med-ical records from a million Estonians. Theproject is a massive undertaking, consideringthat the overall population of this new mem-ber of the European Union is only 1.4 mil-lion. The goals are (i) the identification ofdisease genes through comparison of geno-types within groups of patients with a givendisease and (ii) the creation of a health caredatabase (health history and genealogy)offering free access for Estonians to their ownrecords. The hope is that Estonians will beable to use their country profile to theiradvantage. Estonia has decided that, as asmall country, it will have to concentratestrategically on a few areas of scientificresearch that relate to its existing strengths;molecular biology and population geneticsare two of the selected areas. Estonia is asmall nation, with a good primary health caresystem, where such an ambitious project is

    probably easier to manage that in a largercountry. Its scientific and technologicalinfrastructure are well developed, and laborand overhead costs should be considerablylower than in most western countries. Inaddition, tremendous efforts have been madeto restructure the scientific landscape duringthe period running up to full EU member-ship, which was formally achieved on 1 May2004. However, the Estonian research com-munity still needs more funding from exter-nal sources to develop its science basefurther. If the goals of the Estonian GenomeProject could be achieved successfully, itwould make Estonia an even more attractivepartner for other research communitiesworldwide in their hunt for genes associatedwith disease.

    A final example, albeit one at a ratheradvanced stage of completion, comes fromIceland. After purchasing the IcelandicGenealogic Database from its government,the Icelandic biotech company deCODEGenetics is now using this database, in con-junction with genotypes of some 100,000samples from volunteers, to identify thegenetic bases of common diseases. At theforum, deCODE chief executive KariSteffansson gave an overview of the areas inwhich the company has been particularly suc-cessful. Their genealogy database includesmore than 95% of all those who have lived inIceland since the first census in 1703 andstretches back to the ninth century. In all, thedatabase contains 680,000 entries. The strat-egy developed by deCODE is based on theintegration of genetic, clinical and genealogi-cal data. This enables the identification ofvery small genetic regions shared by relatedpatients and the isolation of key disease genes

    from these regions. Using this strategy,deCODE researchers have isolated 15 specificdisease genes and located genes involved inmore than 25 of the most common diseases.For instance, they identified the STRK1 locuson chromosome 5q12 (ref. 3) and showedthat genetic variation in the phosphodi-esterase gene PDE4D in this region is associ-ated with stroke4. This result wassubsequently replicated in a Scottish strokecohort. A second gene, ALOX5AP, which isinvolved in leukotriene metabolism, was alsoassociated with stroke5. The same gene hasbeen shown to be associated with myocardialinfarction in a British population. Both ofthese disease-specific genes are candidate tar-gets for the development of new pharmaceu-tical agents.

    Scandinavian populations have proven tobe very informative in clinical genetic andepidemiological studies, for several reasons.The countries have relatively small popula-tions, with regions that are relatively isolated,and well-documented family, social andhealth records going back many generations.The national health care systems are publiclyfunded and encompass the whole population.They are completely integrated within thesocial structure