Grant Detail
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LINKAGE IN HUNTINGTON DISEASE AND NEUROFIBROMATOSIS
1 June 1986 - 31 December 1988
NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
Total Funding: $ 598,363
Gusella, et al. have localized the HD gene to chromosome 4 (CH4) in several large multi-generational pedigrees using two linked restriction fragment polymorphisms (RFLPs). We propose to define other RFLPs linked to the HD gene as well as to investigate the possibility of genetic heterogeneity in HD by the sampling of local HD families which we have ascertained. We are constructing a sorted CH4 library for the efficient generation of RFLPs on this chromosome. The generation of CH4 RFLPs will also allow us to pursue two additional lines of research: localization of the gene(s) for peripheral neurofibromatosis (NF) and the further localization of the dentinogenesis imperfecta gene (DGI1). In different family studies NF has been shown to be linked to myotonic dystrophy (DM) on chromosome 19 (CH19) and provisionally to the group specific component (GC) on CH4. DGI1 is linked to GC. We have ascertained and will sample local NF families for the study. The DGI1 families will be obtained through Dr. P. Michael Conneally. The NF families will also be screened with our CH19 RFLPs generated as part of the large study on DM. This will allow us to confirm linkage of NF to either CH19 and/or CH4 as well as to investigate the question of genetic heterogeneity in this disease. Once a linked RFLP is found we will continue to screen our libraries in order to generate additional linkage markers. Closely linked RFLPs will be useful in both carrier detection and prenatal diagnosis. Linkage markers on either side of the disorder can also improve the accuracy of genotypic determinations. Finally, we propose to construct a general linkage map of CH4 and CH19 using our RFLPs in conjunction with CH4 and CH19 genotypic markers. We will use our DGI1, NF, and HD families as well as other large multigenerational source pedigrees (i.e. the Venezuelan pedigree, a family with familial hypercholesterolemia (FCH), and our own DM pedigrees) for the general mapping studies. Multilocus linkage analysis will also be imployed. Thus, these experiments will be instrumental in both helping to further establish the chomosomal location of the HD, NF, and DGI1 genes as well as in providing an available linkage map of CH4 and CH19, enabling investigators to link other genetic disorders to this chromosome.
10 Resulting Publications
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1.
1989N G Laing; T Siddique; R Bartlett; L H Yamaoka; W Y Hung; M A Pericak-Vance; A D Roses
Duchenne muscular dystrophy: detection of deletion carriers by spectrophotometric densitometry.
Clinical genetics 1989;35(6):393-8. -
2.
1989J M Vance; M A Pericak-Vance; L H Yamaoka; M C Speer; G O Rosenwasser; K Small; P C Gaskell; W Y Hung; M J Alberts; C S Haynes
Genetic linkage mapping of chromosome 17 markers and neurofibromatosis type I.
American journal of human genetics 1989;44(1):25-9. -
3.
1989B R Seizinger; G E Farmer; J L Haines; L J Ozelius; K Anderson; B R Korf; D M Parry; M A Pericak-Vance; J J Mulvihill; A Menon
Flanking markers for the gene causing von Recklinghausen neurofibromatosis (NF1).
American journal of human genetics 1989;44(1):30-2. -
4.
1989S R Diehl; M Boehnke; R P Erickson; L M Ploughman; K A Seiler; J L Lieberman; H B Clarke; M A Bruce; E K Schorry; M Pericak-Vance
American journal of human genetics 1989;44(1):33-7. -
5.
1988C S Payne; A D Roses
The molecular genetic revolution. Its impact on clinical neurology.
Archives of neurology 1988;45(12):1366-76. -
6.
1988M A Pericak-Vance; L H Yamaoka; C S Haynes; M C Speer; J L Haines; P C Gaskell; W Y Hung; C M Clark; A L Heyman; J A Trofatter
Genetic linkage studies in Alzheimer's disease families.
Experimental neurology 1988;102(3):271-9. -
7.
1988M A Pericak-Vance; W Y Hung; L Yamaoka; C Haynes; R J Bartlett; J M Vance; J Lee; T Siddique; P C Gaskell; J Stajich
Systematic gene mapping in man: data management considerations.
Australian paediatric journal 1988;24 Suppl 1():87-9. -
8.
1987M A Pericak-Vance; L H Yamaoka; J M Vance; K Small; G O Rosenwasser; P C Gaskell; W Y Hung; M J Alberts; C S Haynes; M C Speer
Genetic linkage studies of chromosome 17 RFLPs in von Recklinghausen neurofibromatosis (NF1).
Genomics 1987;1(4):349-52. -
9.
1987J M Vance; M A Pericak-Vance; M H Bowman; C S Payne; L Fredane; T Siddique; A D Roses; E W Massey
Chorea-acanthocytosis: a report of three new families and implications for genetic counselling.
American journal of medical genetics 1987;28(2):403-10. -
10.
1987M A Pericak-Vance; L H Yamaoka; J M Vance; A S Aylsworth; G O Rossenwasser; P C Gaskell; M J Alberts; W Y Hung; C Haynes; A D Roses
Linkage studies in peripheral neurofibromatosis.
Journal of medical genetics 1987;24(9):530-2.
Scientific Context
This section shows information that has been computed by using the fingerprint of the grant, including related publications, related experts and related grants - all with fingerprints representing significant amounts of overlap between their fingerprint and this grant. The red dots indicate whether those experts or terms actually appear within this grant, showing potential and actual connections.
Related Grants
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1.
HAINES, JONATHAN L
ISOLATION OF GENE DEFECT IN VON HIPPEL-LINDAU DISEASE
1 February 1989 - 31 January 1994
NATIONAL CANCER INSTITUTE
Total Funding: $ 230,974
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2.
GUSELLA, JAMES F
GENETIC AND MOLECULAR STUDIES OF NEUROFIBROMATOSIS 1
1 April 1985 - 31 January 2001
NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
Total Funding: $ 4,830,650
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3.
GROWDON, JOHN H
GENETIC STUDIES OF ALZHEIMER'S DISEASE
1 June 1987 - 31 May 1990
NATIONAL INSTITUTE ON AGING
Total Funding: $ 792,923
Related Publications
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1.
1985J F Gusella; R E Tanzi; P I Bader; M C Phelan; R Stevenson; M R Hayden; K J Hofman; A G Faryniarz; K Gibbons
Deletion of Huntington's disease-linked G8 (D4S10) locus in Wolf-Hirschhorn syndrome.
Nature 1985;318(6041):75-8. -
2.
1993J F Gusella; M E MacDonald
Hunting for Huntington's disease.
Molecular genetic medicine 1993;3():139-58. -
3.
1988J E Richards; T C Gilliam; J L Cole; M L Drumm; J J Wasmuth; J F Gusella; F S Collins
Chromosome jumping from D4S10 (G8) toward the Huntington disease gene.
Proceedings of the National Academy of Sciences of the United States of America 1988;85(17):6437-41.
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