Four chromosomal breakpoints and four new probes mark out a 10-cM region encompassing the fragile-X locus (FRAXA). Academic Article uri icon

Overview

MeSH

  • Blotting, Southern
  • Genetic Linkage
  • Genetic Markers
  • Humans
  • Polymorphism, Restriction Fragment Length
  • Restriction Mapping

MeSH Major

  • DNA Probes
  • Fragile X Syndrome

abstract

  • We report the validation and use of a cell hybrid panel which allowed us a rapid physical localization of new DNA probes in the vicinity of the fragile-X locus (FRAXA). Seven regions are defined by this panel, two of which lie between DXS369 and DXS296, until now the closest genetic markers that flank FRAXA. Of those two interesting regions, one is just distal to DXS369 and defined by probe 2-71 (DXS476), which is not polymorphic. The next one contains probes St677 (DXS463) and 2-34 (DXS477), which are within 130 kb and both detect TaqI RFLPs. The combined informativeness of these two probes is 30%. We cloned from an irradiation-reduced hybrid line another new polymorphic probe, Do33 (DXS465; 42% heterozygosity). This probe maps to the DXS296 region, proximal to a chromosomal breakpoint that corresponds to the Hunter syndrome locus (IDS). The physical order is thus Cen-DXS369-DXS476-(DXS463,DXS477)-(DXS296, DXS465)-IDS-DXS304-tel. We performed a linkage analysis for five of these markers in both the Centre d'Etude du Polymorphisme Humain families and in a large set of fragile-X families. This establishes that DXS296 is distal to FRAXA. The relative position of DXS463 and DXS477 with respect to FRAXA remains uncertain, but our results place them genetically halfway between DXS369 and DXS304. Thus the DXS463-DXS477 cluster defines presently either the closest proximal or the closest distal polymorphic marker with respect to FRAXA. The three new polymorphic probes described here have a combined heterozygosity of 60% and represent a major improvement for genetic analysis of fragile-X families, in particular for diagnostic applications.

publication date

  • January 1991

has subject area

  • Blotting, Southern
  • DNA Probes
  • Fragile X Syndrome
  • Genetic Linkage
  • Genetic Markers
  • Humans
  • Polymorphism, Restriction Fragment Length
  • Restriction Mapping

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC1682738

PubMed ID

  • 1670748

Additional Document Info

start page

  • 108

end page

  • 116

volume

  • 48

number

  • 1