CMT DISEASE--LOCALIZATION OF TYPES 1A AND 2

Project: Research project

Description

Charcot-Marie-Tooth disease (CMT) is the most common inherited
neuropathy characterized by peroneal and distal muscle atrophy at the
extremities. Clinically homogenous, the disorder is separated into two
types, CMT 1 and CMT 2. These two types can be differentiated
pathologically and physiologically using Nerve Conduction Studies (NCS).
We initially localized CMT la to chromosome 17 and have recently
sublocalized this form to the 17pll.2 region of chromosome 17. This
proposal describes an approach to continue our localization of CMT la.
In addition, CMT2 families are identified through our work on CMT la. We
also propose to apply linkage analysis to CMT 2 to determine chromosomal
location of this disorder. The approach towards localizing the CMT la
gene includes expansion of family data, identification of probes using
existing libraries (chromosome 17 cosmid library, L4 microcell link
library), and the development of new plasmid libraries from chromosome 17
radiation hybrids spanning this region. Multipoint linkage analysis will
be used for further localization with these probes until close flanking
markers are found. Application of current methodology such as PCR, STS,
CA repeats, single strand conformation polymorphisms and nucleotide
analog polymorphisms will be used with selected cloned markers to
increase heterozygosity of these probes. As close-flanking markers are
found, concurrent physical mapping using pulse field gel electrophoresis,
cosmid, linkage and hopping libraries and yeast artificial chromosomes
will be used to map the region surrounding the CMT la gene. Candidate
probes can be screened against zoo blots and a peripheral nerve cDNA
library. A similar approach will be applied when the gene for CMT 2 is
located.
StatusFinished
Effective start/end date5/1/913/31/01

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $190,400.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

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tooth diseases
Charcot-Marie-Tooth Disease
Peripheral Nervous System Diseases
chromosomes
linkage (genetics)
Demyelinating Diseases
Genes
Haplotypes
Chromosomes
Organism Cloning
muscular atrophy
single-stranded conformational polymorphism
physical chromosome mapping
peripheral nerves
zoos
gel electrophoresis
Chromosomes, Human, Pair 17
heterozygosity
plasmids
nerve tissue

ASJC

  • Medicine(all)
  • Neuroscience(all)