Project: Research project

Project Details


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.
Effective start/end date1/1/901/1/90


  • National Institute of Neurological Disorders and Stroke
  • National Institute of Neurological Disorders and Stroke


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