Genetic and physical mapping of the Chediak-Higashi syndrome on chromosome 1q42-43

Am J Hum Genet. 1996 Sep;59(3):625-32.


The Chediak-Higashi syndrome (CHS) is a severe autosomal recessive condition, features of which are partial oculocutaneous albinism, increased susceptibility to infections, deficient natural killer cell activity, and the presence of large intracytoplasmic granulations in various cell types. Similar genetic disorders have been described in other species, including the beige mouse. On the basis of the hypothesis that the murine chromosome 13 region containing the beige locus was homologous to human chromosome 1, we have mapped the CHS locus to a 5-cM interval in chromosome segment 1q42.1-q42.2. The highest LOD score was obtained with the marker D1S235 (Zmax = 5.38; theta = 0). Haplo-type analysis enabled us to establish D1S2680 and D1S163, respectively, as the telomeric and the centromeric flanking markers. Multipoint linkage analysis confirms the localization of the CHS locus in this interval. Three YAC clones were found to cover the entire region in a conting established by YAC end-sequence characterization and sequence-tagged site mapping. The YAC contig contains all genetic markers that are nonrecombinant for the disease in the nine CHS families studied. This mapping confirms the previous hypothesis that the same gene defect causes CHS in human and beige pheno-type in mice and provides a genetic framework for the identification of candidate genes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chediak-Higashi Syndrome / genetics*
  • Chromosome Mapping*
  • Chromosomes, Artificial, Yeast / genetics
  • Chromosomes, Human, Pair 1 / genetics*
  • Female
  • Genetic Markers
  • Haplotypes
  • Humans
  • Lod Score
  • Male
  • Mice
  • Pedigree
  • Sequence Tagged Sites


  • Genetic Markers