Postal address: The Rudbeck laboratory, Uppsala University Children’s Hospital, SE-751 85 Uppsala, Sweden
Visiting address: Dag Hammarskjölds väg 20
Web page: http://www.genpat.uu.se/

Contact person: Dr. Niklas Dahl, phone +46 (0)18 6112799

On the first of January 2011, the unit for Clinical Immunology fused with the Department of Genetics and Pathology, creating the Department of Immunology, Genetics and Pathology, IGP.

South Asia related research at the department:

Prof. Niklas Dahl leads a research group working on Medical Genetics and Genomics. They are involved in a collaboration project with the National Institute for Biotechnology and Genetic Engineering (NIBGE) in Faisalabad, Pakistan. In November 2008 Prof. Dahl received a Swedish Research Links (Asian–Swedish research partnership programme) grant – SEK 600 000 for three years (2009-11) for this project titled ”Inherited and disabling diseases in Pakistan: Molecular understanding and counselling”. See the full list of South Asia related projects given Swedish Research Links gants 2008.
The collaboration partner on the Pakistani side is Dr. Shahid M. Baig at the Health Division, NIBGE. Since early 2007, Dr. Baig has visited Uppsala twice to set practical details for this collaboration. (Dr. Baig is also involved in another Nordic research collaboration project on ”Molecular genetics of Pakistani families with monogenic disorders” with the PANUM Institute at the University of Copenhagen).
Two PhD students from NIBGE (Mahmood Rasool and Sadia Nawaz) have also trained at Uppsala University, Rudbeck lab. for a time period of 6 months each. The initial efforts have been covered by minor funding support from the Indevelop fund (Uppsala University).

The project is an effort to establish at a long term scientific cooperation between NIBGE, Pakistan and Uppsala University. The high degree of consanguineous marriages in the Pakistani population is an important responsible factor for their high frequency of congenital malformations and/or chronic disease. It also constitutes a unique source to reveal the genetic basis of many traits and this proposal will lead to the identification of novel mutant genes behind congenital disorders. This will add crucial links to specific mechanisms in the development of several tissues and may pin-point at specific targets for future therapeutic interventions.
In the short term, the expected outcome of this project is improved diagnostics and counseling for several disorders which are relatively prevalent in Pakistan. The project will also contribute to the PhD-education of several registered students at NIBGE, Faisalabad and at Uppsala University.
Other researchers engaged in the project on a part- to full-time have been in Uppsala: PhD candidates Miriam Entesarian(later post-doc researcher at Karolinska Institutet, Stockholm), Anne Sophie Fröjmark and Joakim Klar; and at NIBGE: Aysha Azhar.
Background: Consanguinity (cousin, second- or third cousin) increases the probability for deleterious recessive genes to manifest. Studies of the correlation of inbreeding with congenital malformations have revealed elevated levels of malformations (9.1-12.4%) among offspring of consanguineous as compared to non-consanguineous marriages (1.0-5.3%. Hospital based surveys conducted in the UK and Pakistan showed a high prevalence (50-83%) of consanguineous marriages amongst Pakistanis which is one of the highest frequency known. The frequency of birth defects amongst Pakistani children is in the range of 12.3-17% of which a large proportion is attributed to autosomal recessive traits (monogenic) and consanguinity. The frequency of birth defects in Europe is approximately 4% and one major reason for the lower frequency is the low rate of consanguineous marriages (0-3%).
A large proportion of the Mendelian congentital traits in the Pakistani population are caused by yet undefined disease genes. Consequently, the pathophysiological mechanisms remain unclear.
With the development in human genomics over the last years there are now methods developed for the rapid identification of recessive gene mutations in founder populations. The group around Dr. Dahl, Uppsala University, Rudbeck lab. have recently shown that disease genes may be identified in small founder populations using recently developed DNA-array analysis at high resolution. This technique is applicable for the identification of novel disease genes in single consanguineous pedigrees .

Dr. Baig at the Health Division, National Institute for Biotechnology and Genetic Engineering (NIBGE), Faisalabad has over the last years developed a unit for clinical characterisation and laboratory analysis of inherited disorders in Pakistan. The projects have focused on the clinical delineation of novel human phenotypes (see figure to the right) as well as molecular diagnosis of common recessive traits in Pakistan.The combined competence and accessible resources in the groups headed by Dr. Baig and Dr. Dahl provide an ideal platform for synergistic effects according to the specific aims. The project will therefore strengthen this recent initiative for a long-term and productive scientific cooperation.

Associate Professor Marie Allen has previously been involved in a collaboration project with the Faculty of Medicine, Dept. of Biochemistry and Molecular Biology, University of Colombo, Sri Lanka. The project also involved the Dept. of Pharmacognosy at Uppsala University; and the Dept. of Biotechnology, Lund University. It was titled ”Capacity building in biochemistry, molecular biology, and gene technology” and was funded by the International Science Programme, Uppsala University.