GENOMICS $420-428 (1991) A Centromere-Based Genetic Map of the Short Arm of Human Chromosome 6 HELENE BLANCH&* HUDA Y. ZOGHBI,~ ETHYLIN WANG JABS,* BEATRICE DE GOUYON,* RENATA ZUNEC,**§ JEAN DAMSET,* AND HOWARD M. CANN**’ *Centre d’Etude du Polymorphisme Humain (CEPH), 75070 Paris, France; tDepartment of Pediatrics and Institute for Molecular Genetics, Baylor College of Medicine, Houston, Texas 77030; SCenter for Medical Genetics, Department of Pediatrics, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205; and §Tissue Typing Centre, Medical Faculty, University of Zagreb, 4 100 Zagreb, Yugoslavia Received July 26, 1990, revised October 26, 1990 A genetic map of the short arm of chromosome 6 (6~) has been constructed with 20 genetic markers that define 16 loci, including a locus at the centromere. The 40 CEPH fam- ilies and, for 4 loci, 13 additional Utah families were geno- typed. All 16 loci form a single linkage group extending from near the telomeric region to the centromere, covering 159 CM (Haldane) on the female map and 94 CM on the male map. Sex differences in recombination frequencies are noted for the 6p map, with an excess occurring in males at the distal end. The genetic order of loci is consistent with their physical localization on 6p. Proximal to the three most distal loci on the map, markers are especially dense, providing an extended region on 6p useful for localizing genes of interest. c 1991 Academic Press. Inc. INTRODUCTION Primary genetic maps of all the human chromo- somes are important tools for localizing genesof inter- est (Botstein et al., 1980). Recently, human genes ho- mologous to those in and close to the murine t com- plex have been located on both arms of chromosome 6 (Bibbins et al., 1989), and a gene for one form of spi- nocerebellar ataxia (SCAl) has been genetically local- ized on the short arm (6~) (Yakura et al., 1974; Mor- ton et al., 1980; Rich et al., 1987; Zoghbi et al., 1988). A primary linkage map of chromosome 6 is the first step in precisely localizing these genes. Until recently, ge- netic and physical mapping activities on this chromo- some have been directed at the region on 6p contain- ing the human major histocompatibility complex (the HLA region). As the HLA region covers a small frac- ’ To whom correspondence should be addressed at Centre d’Etude du Polymorphisme Humain (CEPH), 27 rue Juliette Dodu, 75010 Paris, France. tion of 6p (roughly 5%), there is clearly more work to do in developing a primary genetic map. Four genetic maps of 6p have been published (Leach et al., 1986; Donis-Keller et al., 1987; Donis- Keller and Helms, 1990; Zoghbi et al., 1990), each con- structed with genotypes generated from DNA from the CEPH reference families (Dausset et al., 1990). The genetic map of 6p has now been extended with the 16-point continuous linkage map that we present here. The map spans most of 6p, from near the telo- merit region to the centromere which is localized on the map genetically. MATERIALS AND METHODS Families Genotypes for 20 genetic markers were generated from blood and DNA of lymphoblastoid cell lines (LCLs) from the 40 families of the CEPH reference panel (Dausset et al., 1990). Genotypes for 4 of these markers, D6S7, D6S8, D6S5, and GLOl (see Table l), were generated from 17 of the CEPH families and 13 additional Utah families by Leach et al. (1986). Genetic Markers The 20 markers used to construct this map of 6p are presented in Table 1; 16 loci are defined by these markers. Locus names reflect official HGMlO no- menclature (Human Gene Mapping 10, 1989) (Table 1). HLA-A, HLA-B, and HLA-DR phenotypes were determined by serological typing (Histocompatibility Testing, 1987). Electrophoresis of erythrocyte ly- sates, followed by staining with specific substrate, re- vealed phenotypes for GLOl (Kompf et al., 19751. Thirteen cloned DNA sequences were used to geno- type for DNA polymorphisms. 0888.7543/91 $3.00 Copyright C: 1991 by Academic Press. Inc. All rights of reproduction in any form reserved. 420