Eric D. Lynch

Chromosome 1 Charcot-Marie-Tooth disease (CMT1B) locus in the Fcγ receptor gene region

Roger V. Lebo l, Phillip E Chance 2, Peter J. Dyck 3, Ma. Theresa Redila-Flores 1, Eric D. Lynch 1, Mitchell S. Golbus 1, Thomas D. Bird 4, Mary Claire King 5, Lee A. Anderson 1,5, Jeffrey Hall 5, Joop Wiegant 6, Zharong Jiang 1, Paul F. Dazin 1, Hope H. Punnett 7, Steven A. Schonberg 1, Kevin Moore s, Marcia M. Shull 9, Sandra Gendler j~ Orest Hurko ]l, Robert E. Lovelace ]2, Norman Latov 12, James Trofatter 13, P. Michael Conneally 13

Rare McArdle disease locus polymorphic site on 11q13 contains CpG sequence

SummaryWhen probes throughout the McArdle disease (myophosphorylase) gene region were used to search for DNA polymorphisms, only an MspI polymorphism was found in 94 enzyme-probe combinations. Along with an insertion/deletion polymorphism more 3′ to the gene locus, these polymorphisms will be informative in 75% of at-risk patients. These results contrast strikingly to the six polymorphic sites detected in 15 enzyme-probe combinations in the homologous Hers disease (liver phosphorylase) gene region. This single MspI polymorphic site includes a CpG sequence of known increased mutability suggesting that DNA regions with rare polymorphisms will have most polymorphic sites at sequences with enhanced mutability. Fluorescence in situ hybridization sublocalized this gene to proximal band 11q13, establishing a point of cross-reference between the physical and genetic maps.

Multicolor fluorescence in situ hybridization and pulsed field electrophoresis dissect CMT1B gene region

SummaryWe have used multicolor fluoresence in situ hybridization of banded chromosomes to orient FcγRII and clone 1054 on a single early metaphase chromosome band (1q22) representing about 2% of the physical map of chromosome 1 in the Charcot-Marie-Tooth (CMT1B) gene region. These two cloned fragments are on the same partially digested 900-kb MluI fragment detected by pulsed field gel electrophoresis. When applied to data from an earlier study, multicolor in situ hybridization results further refined the CMT1B genetic location from an 18 cM interval to a 6 cM interval and the physical map from 15% of chromosome 1 to 3% of chromosome 1. Occasionally the three FcγRII immunoglobulin receptor genes within the 200-kb region are resolved in individual metaphase chromatids.

Regional assignment of the human keratin 5 (KRT5) gene to chromosome 12q near D12S14 by PCR analysis of somatic cell hybrids and multicolor in situ hybridization.

Keratin 5 is the major type II keratin of the basal cells of epidermis and of other stratified epithelia. With its type I partner, keratin 14, it constitutes a major fraction of the cytoskeleton of the basal cells. Because the inheritance of epidermolysis bullosa simplex, a disease of epidermal basal cell fragility, was mapped in one family to chromosome 12q close to D12S14, we undertook to localize the gene for keratin 5. Polymerase chain reaction analysis of somatic cell hybrids mapped the keratin 5 gene to chromosome 12, and multicolor fluorescence in situ hybridization localized it to 12q very near D12S14. This sublocalization exemplifies the utility of in situ physical localization in assessing the candidacy of genes thought to underlie inherited disorders.