MAMMALIAN REPETITIVE SEQUENCES AS A GENETIC TOOL

  • Hardies, Stephen C (PI)

Project: Research project

Project Details

Description

Species-specific hybridization probes will be constructed that are
capable of distinguishing the LINES ONE sequences of Mus domesticus
and Mus spretus. This is possible because concerted evolution of
the LINE ONES repeats causes them to accumulate species-specific
mutations. Oligonucleotide probes that cover these species-
specific mutations will be synthesized. Several such probes have
been synthesized and characterized to document the feasibility of
this approach. Within 60 kilobases of any gene in the mouse genome
there should be a species-specific marker that is detectable by
these probes. This marker system will be used with Mus
domesticus/Mus spretus hybrids as a general tool for mapping and
isolating genes. It is proposed to use the species-specific probes to address the
W and Steel loci. Mutations at these two loci both cause
developmental defects in blood cells germ cells, and pigment cells.
W mutants are thought to carry defects in the respective stem
cells; Steel mutants are thought to be defective in the environment
with which the stem cells must interact. The experimental strategy
requires the breeding of congenic strains carrying Mus spretus DNA
at the target locus on a Mus domesticus background or vice versa.
Arrangements have been made to gain access to such hybrids the
species-specific probes will be used to isolate clones from the
genomic sequences in the congenic region. The use of species-specific probes for following the segregation
of the two parental genomes in Mus spretus/Mus domesticus hybrids
is also described. It is proposed to monitor the reduction in the
parental loss of particular markers, or the chromosomal
configuration could be monitored. Choosing the offspring to parent
each successive generation based on this information would increase
the speed and range of genetic techniques involving Mus spretus/Mus
domesticus hybrids.
StatusFinished
Effective start/end date2/1/881/31/91

Funding

  • National Institutes of Health
  • National Institutes of Health

ASJC

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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