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From:
SUNTOU TOURAY <[log in to unmask]>
Reply To:
The Gambia and related-issues mailing list <[log in to unmask]>
Date:
Sat, 26 Apr 2008 10:07:22 +0100
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  A national DNA bank in The Gambia, West Africa,
  and genomic research in developing countries
  To the editor:
  The Gambian National DNA Bank, the first
  National Bio-Bank developed in Africa,
  was funded in November 2000 by the
  Medical Research Council (MRC) as one of
  14 DNA collection sites established to
  study the genetics of complex diseases. One
  of these sites is housed at the MRC
  Laboratories in The Gambia and has a
  special, though not exclusive, focus on
  malaria, HIV and tuberculosis. Additional
  projects include analyses of genome
  diversity in West African populations and a
  collection of twin-sister pairs to study the
  genetic basis of dizygotic twins (&#8764;2% of
  live births in the country). So far, more
  than 30,000 DNA samples have been
  collected, with many ongoing studies and
  more planned.
  For the first time in a sub-Saharan country,
  a centralized structure and database for
  archiving DNA samples has been created, in
  collaboration with the Jean Dausset
  Foundation-CEPH. The bank is regulated by
  guidelines (Supplementary Note online) for
  sample collection, archiving, data storage and
  privacy protection, which were developed and
  approved by the MRC, the MRC Laboratories
  Scientific Coordinating Committee and by the
  Gambia Government/MRC Joint Ethics
  Committee. The Guidelines, which are
  enforced by these Committees, stemmed from
  the need to adapt to the local reality the many
  existing recommendations on bio-banking,
  privacy protection, genetics research and,
  generally, on medical research in developing
  countries (http://www3.who.int/whosis/
  genomics/pdf/genomics08.pdf,
  http://www.mrc.ac.uk/pdf-devsoc.pdf,
  http://www.mrc.ac.uk/pdf-tissue_guide_fin.
  pdf, http://www.nuffieldbioethics.org/
  publications/pp_0000000013.asp).
  The Gambian DNA Bank promotes
  sharing of information and resources with
  centers around the world, and one of its
  ultimate goals is health improvement. In the
  short term, benefits should accrue to the
  participants in the studies. A recent example
  is a large project on genetic and
  environmental factors for susceptibility to
  tuberculosis, designed as a household
  association and family-based study and
  carried out in The Gambia, Guinea-Bissau
  and Guinea-Conakry1. The project focused
  on the systematic detection of tuberculosis
  cases in the families of individuals with
  tuberculosis and controls. Clinical services
  © 2004 Nature Publishing Group http://www.nature.com/naturegenetics
  CORRESPONDENCE
  were considerably augmented within the
  framework of the genetic study, to the benefit
  of the populations involved.
  During research projects at the MRC Unit
  in The Gambia, biological samples (mostly
  blood, buffy coats and peripheral blood
  mononuclear cells) were taken and stored at a
  time when molecular genetics was still in its
  infancy. The process of obtaining consent has
  evolved enormously over time, and in the
  past, samples may have been taken from
  subjects who were not made specifically aware
  that the samples were going to be used for
  genetic studies. The Guidelines now regulate
  the use of these archived DNA specimens: in
  almost all circumstances they can be used
  only after anonymization and unlinking
  (Supplementary Note online), and all use
  requires approval by the Ethics Committee.
  Regrettably, most African countries do not
  have the infrastructure necessary to carry out
  genomic studies, and so most scientific
  exchange has taken place with developed
  countries. The Ethics Committee has a key
  role in sanctioning shipment of any samples
  to external collaborators. The Committee
  evaluates the specificity of the project and reevaluates
  projects in case their focus changes
  over time. All transfer of DNA samples to
  collaborators is accompanied by signed
  agreements and detailed documentation
  describing the projects involved. The review
  of sample transfer to third parties is
  compulsory and is not permitted from one
  collaborator to another without consent of
  the Ethics Committee.
  In the long term, understanding genetic
  determinants of infection can lead to
  prevention and improved treatment, but this
  does not mean that genetic research will cure
  infectious diseases. Even more complicated is
  the situation of population-genetics studies
  promoted by interest in the greater genomic
  diversity found in Africans compared with
  Europeans and Asians, and consistent with the
  hypothesis of an African origin of modern
  humans. Where sampling is not part of
  research aimed directly at disease, the
  connection to health interventions seems
  weak. But this does not imply that studies on
  genome diversity should not be done, for the
  contribution of both inter- and intraethnic
  genetic variability comparisons is crucial in
  our understanding of immunity to infections.
  For example, the findings that West African
  Fulani have fewer malaria attacks and lower
  parasitemia by Plasmodium falciparum than
  two sympatric ethnic groups2, and that they
  have intragroup variation in immune
  responses to malaria3, open the possibility of
  identifying genetic factors determining
  malarial immunity. Immunogenetic
  associations with infectious disease, such as
  the association between HLA-B53 and
  resistance to severe malaria found in Gambian
  children4, can affect vaccine development.
  The ethics guidelines adopted for the
  Gambian National DNA Bank do not
  presume to be the last word on the matter.
  Rather, we hope their publication will
  stimulate discussion of the appropriate way
  to regulate genomic research in developing
  countries. We hope that our initiative will be
  seen as an important experience in a complex
  and fast-evolving venture from which Africa
  should not be excluded, and as a possible
  template to be adapted by similar initiatives
  in other parts of the world.
  Note: Supplementary information is available on the
  Nature Genetics website.
  ACKNOWLEDGMENTS
  This work was supported by the MRC (UK) to G.S.
  Giorgio Sirugo1, Maarten Schim Van Der Loeff1,
  Omar Sam2, Ousman Nyan3, Margaret Pinder1,
  Adrian V Hill4, Dominic Kwiatkowski4,
  Andrew Prentice1,5, Claudia de Toma6,
  Howard M. Cann6, Mathurin Diatta1,
  Muminatou Jallow1,7, Gareth Morgan1,
  Malcolm Clarke8, Tumani Corrah1,
  Hilton Whittle1 & Keith McAdam1,5
  1MRC Laboratories, PO Box 273, Banjul, The
  Gambia. 2Department of State for Health, Banjul,
  The Gambia. 3University of The Gambia, School
  of Medicine, The Gambia. 4Wellcome Trust Centre
  for Human Genetics, University of Oxford, UK.
  5London School of Hygiene and Tropical
  Medicine, UK. 6Fondation Jean-Dausset-CEPH,
  Paris, France. 7Royal Victoria Teaching Hospital,
  Banjul, The Gambia. 8Gambian Government /
  MRC Laboratories Joint Ethics Committee,
  Fajara, The Gambia. Correspondence should be
  addressed to G.S. ([log in to unmask]).
  1. Lienhardt, C. et al. Am. J. Epidemiol. 155,
  1066–1073 (2002).
  2. Modiano, D. et al. Proc. Natl. Acad. Sci. USA 93,
  13206–13211 (1996).
  3. Luoni, G. et al. Genes Immun. 2, 411–414 (2001).
  4. Hill, A.V. et al. Nature 352, 595–600 (1991).
  786 VOLUME 36 | NUMBER 8 | AUGUST 2004 NATURE GENETICS
  Evidence for lateral gene transfer from salmonids to
  two Schistosome species
  To the editor:
  Two detailed studies of the genomes of Asian
  and African and American schistosomes were
  recently published1,2. In the former, some
  13,131 gene clusters from Schistosoma
  japonicum EST clones were analyzed and
  their hypothetical protein products were
  compared with those of model organisms,
  uncovering about 30% homologous proteins
  (at E &#8804; 10–10). In their report on the
  evolutionary implications of their
  sequencing project1, however, the authors
  did not mention that one of their libraries
  (SjC7/94) contained many inserts with high
  homology to genomic DNA of salmonid fish.
  This was recorded in GenBank, in which it
  was stated that these homologous inserts
  amounted to 2–3% of the library clones. Our
  analysis showed that more than 10% of the
  SjC7/94 clones matched (E &#8804; 10–10) DNA of
  salmonid fish; more than 95% of these were
  the best matches found in the entire nr
  database.
  Our analysis of the SjC7/94 library also
  showed that nearly all of the salmonidhomologous
  inserts are found in noncoding
  regions of the salmonid genes and seem to
  comprise salmon-specific mobile genetic
  elements. For example, the clone BU712912
  contains a 480-bp sequence that is almost
  identical (94% identity; E = 0) to the
  Oncorhynchus mykiss LINE Rsg-1 (ref. 3);
  searches of the mammalian database for
  similar sequences produced no matches
  (E > 0.05), and none were found in other
  invertebrates (E > 0.06). The SjC7/94 library
  also contains sequences homologous to the
  salmonid SINEs SmaI (found only in
  Oncorhynchus keta and Oncorhynchus
  gorbuscha, possibly after lateral transfer4;
  E = 90–50) and HpaI (found in all salmonids;
  E = 10–78). There are even S. japonicum
  sequences homologous (E = 10–27) to FokI,
  which is supposed to be specific to the genus
  Salvelinus4,5; these show a higher level of
  identity than is seen in other salmonids.
  To verify the presence of these sequences in
  the schistosome genome and to elucidate
  more about their expression, we carried out
  PCR using primers designed to amplify six of
  these salmonid-specific sequences, initially
  © 2004

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