Heather Fraser

Publications (4)2.47 Total impact

• Chapter: Natural Genetic Variants Influencing Type 1 Diabetes in Humans and in the NOD Mouse

  Linda S. Wicker, Carolyn L. Moule, Heather Fraser, Carlos Penha-Goncalves, Dan Rainbow, Valerie E. S. Garner, Giselle Chamberlain, Kara Hunter, Sarah Howlett, Jan Clark, [......], Paul Tiffen, Joanna Howson, Barry Healy, Luc J. Smink, Amanda Kingsnorth, Paul A. Lyons, Simon Gregory, Jane Rogers, John A. Todd, Laurence B. Peterson
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  ABSTRACT: The understanding of the genetic basis of type 1 diabetes and other autoimmune diseases and the application of that knowledge to their treatment, cure and eventual prevention has been a difficult goal to reach. Cumulative progress in both mouse and human are finally giving way to some successes and significant insights have been made in the last few years. Investigators have identified key immune tolerance-associated phenotypes in convincingly reliable ways that are regulated by specific diabetes-associated chromosomal intervals. The combination of positional genetics and functional studies is a powerful approach to the identification of downstream molecular events that are causal in disease aetiology. In the case of type 1 diabetes, the availability of several animal models, especially the NOD mouse, has complemented the efforts to localize human genes causing diabetes and has shown that some of the same genes and pathways are associated with autoimmunity in both species. There is also growing evidence that the initiation or progression of many autoimmune diseases is likely to be influenced by some of the same genes.
  10/2008: pages 57 - 75; , ISBN: 9780470021392
• Article: Natural genetic variants influencing type 1 diabetes in humans and in the NOD mouse.

  Linda S Wicker, Carolyn L Moule, Heather Fraser, Carlos Penha-Goncalves, Dan Rainbow, Valerie E S Garner, Giselle Chamberlain, Kara Hunter, Sarah Howlett, Jan Clark, [......], Paul Tiffen, Joanna Howson, Barry Healy, Luc J Smink, Amanda Kingsnorth, Paul A Lyons, Simon Gregory, Jane Rogers, John A Todd, Laurence B Peterson
  [show abstract] [hide abstract]
  ABSTRACT: The understanding of the genetic basis of type 1 diabetes and other autoimmune diseases and the application of that knowledge to their treatment, cure and eventual prevention has been a difficult goal to reach. Cumulative progress in both mouse and human are finally giving way to some successes and significant insights have been made in the last few years. Investigators have identified key immune tolerance-associated phenotypes in convincingly reliable ways that are regulated by specific diabetes-associated chromosomal intervals. The combination of positional genetics and functional studies is a powerful approach to the identification of downstream molecular events that are causal in disease aetiology. In the case of type 1 diabetes, the availability of several animal models, especially the NOD mouse, has complemented the efforts to localize human genes causing diabetes and has shown that some of the same genes and pathways are associated with autoimmunity in both species. There is also growing evidence that the initiation or progression of many autoimmune diseases is likely to be influenced by some of the same genes.
  Novartis Foundation symposium 02/2005; 267:57-65; discussion 65-75.
• Source

  Available from: Kjersti Skjold Rønningen

  Article: Construction and analysis of tag single nucleotide polymorphism maps for six human-mouse orthologous candidate genes in type 1 diabetes.

  Lisa M Maier, Deborah J Smyth, Adrian Vella, Felicity Payne, Jason D Cooper, Rebecca Pask, Christopher Lowe, John Hulme, Luc J Smink, Heather Fraser, [......], Dag E Undlien, Kjersti S Rønningen, Cristian Guja, Constantin Ionescu-Tîrgoviste, David A Savage, David P Strachan, Laurence B Peterson, John A Todd, Linda S Wicker, Rebecca C Twells
  [show abstract] [hide abstract]
  ABSTRACT: One strategy to help identify susceptibility genes for complex, multifactorial diseases is to map disease loci in a representative animal model of the disorder. The nonobese diabetic (NOD) mouse is a model for human type 1 diabetes. Linkage and congenic strain analyses have identified several NOD mouse Idd (insulin dependent diabetes) loci, which have been mapped to small chromosome intervals, for which the orthologous regions in the human genome can be identified. Here, we have conducted re-sequencing and association analysis of six orthologous genes identified in NOD Idd loci: NRAMP1/SLC11A1 (orthologous to Nramp1/Slc11a1 in Idd5.2), FRAP1 (orthologous to Frap1 in Idd9.2), 4-1BB/CD137/TNFRSF9 (orthologous to 4-1bb/Cd137/Tnrfrsf9 in Idd9.3), CD101/IGSF2 (orthologous to Cd101/Igsf2 in Idd10), B2M (orthologous to B2m in Idd13) and VAV3 (orthologous to Vav3 in Idd18). Re-sequencing of a total of 110 kb of DNA from 32 or 96 type 1 diabetes cases yielded 220 single nucleotide polymorphisms (SNPs). Sixty-five SNPs, including 54 informative tag SNPs, and a microsatellite were selected and genotyped in up to 1,632 type 1 diabetes families and 1,709 cases and 1,829 controls. None of the candidate regions showed evidence of association with type 1 diabetes (P values > 0.2), indicating that common variation in these key candidate genes does not play a major role in type 1 diabetes susceptibility in the European ancestry populations studied.
  BMC Genetics 01/2005; 6:9. · 2.47 Impact Factor
• Article: Construction and analysis of tag single nucleotide polymorphism maps for six human-mouse orthologous candidate genes in type 1 diabetes

  Lisa Maier, Deborah Smyth, Adrian Vella, Felicity Payne, Jason Cooper, Rebecca Pask, Christopher Lowe, John Hulme, Luc Smink, Heather Fraser, [......], Dag Undlien, Kjersti Rønningen, Cristian Guja, Constantin Ionescu-Tîrgovişte, David Savage, David Strachan, Laurence Peterson, John Todd, Linda Wicker, Rebecca Twells
  [show abstract] [hide abstract]
  ABSTRACT: Abstract Background One strategy to help identify susceptibility genes for complex, multifactorial diseases is to map disease loci in a representative animal model of the disorder. The nonobese diabetic (NOD) mouse is a model for human type 1 diabetes. Linkage and congenic strain analyses have identified several NOD mouse Idd (insulin dependent diabetes) loci, which have been mapped to small chromosome intervals, for which the orthologous regions in the human genome can be identified. Here, we have conducted re-sequencing and association analysis of six orthologous genes identified in NOD Idd loci: NRAMP1/SLC11A1 (orthologous to Nramp1/Slc11a1 in Idd5.2 ), FRAP1 (orthologous to Frap1 in Idd9.2 ), 4-1BB/CD137/TNFRSF9 (orthologous to 4-1bb/Cd137/Tnrfrsf9 in Idd9.3 ), CD101/IGSF2 (orthologous to Cd101/Igsf2 in Idd10 ), B2M (orthologous to B2m in Idd13 ) and VAV3 (orthologous to Vav3 in Idd18 ). Results Re-sequencing of a total of 110 kb of DNA from 32 or 96 type 1 diabetes cases yielded 220 single nucleotide polymorphisms (SNPs). Sixty-five SNPs, including 54 informative tag SNPs, and a microsatellite were selected and genotyped in up to 1,632 type 1 diabetes families and 1,709 cases and 1,829 controls. Conclusion None of the candidate regions showed evidence of association with type 1 diabetes ( P values > 0.2), indicating that common variation in these key candidate genes does not play a major role in type 1 diabetes susceptibility in the European ancestry populations studied.
  BMC Genetics. 01/2005;