title: The PML gene is linked to a megabase-scale insertion/deletion restriction fragment length polymorphism.
abstract: The PML gene located on chromosome band 15q22 is involved with the RAR alpha locus (17q21) in a balanced reciprocal translocation uniquely observed in acute promyelocytic leukemia. Physical mapping studies by pulsed-field gel electrophoresis revealed that the PML gene is flanked by two CpG islands that are separated by a variable distance in normal individuals. Several lines of evidence demonstrate that this is the consequence of a large insertion/deletion polymorphism linked to the PML locus: (1) overlapping fragments obtained with a variety of rare-cutting restriction enzymes demonstrated the same variability in distance between the flanking CpG islands; (2) mapping with restriction enzymes insensitive to CpG methylation confirmed that the findings were not a consequence of variable methylation of CpG dinucleotides; (3) the polymorphism followed a Mendelian inheritance pattern. This polymorphism is localized 3' to the PML locus. There are five common alleles, described on the basis of BssHII fragments, ranging from 220 to 350 kb with increments of approximately 30 kb between alleles. Both heterozygous (61%) and homozygous (39%) patterns were observed in normal individuals. Megabase-scale insertion/deletion restriction fragment length polymorphisms are very rare and have been described initially in the context of multigene families. Such structures have been also reported as likely regions of genetic instability. High-resolution restriction mapping of this particular structure linked to the PML locus is underway.
authors.affiliation: Molecular Biology Program, Sloan-Kettering Institute, New York, New York 10021, USA.
authors.forename: A
authors.initials: A
authors.lastname: Goy
authors.forename: T
authors.initials: T
authors.lastname: Passalaris
authors.forename: Y H
authors.initials: YH
authors.lastname: Xiao
authors.forename: W H
authors.initials: WH
authors.lastname: Miller
authors.forename: D S
authors.initials: DS
authors.lastname: Siegel
authors.forename: A D
authors.initials: AD
authors.lastname: Zelenetz
mesh_terms: D000483:Alleles; D002884:Chromosomes, Human, Pair 15; D002886:Chromosomes, Human, Pair 17; D015252:Deoxyribonucleases, Type II Site-Specific; D016521:Electrophoresis, Gel, Pulsed-Field; D005796:Genes; D008040:Genetic Linkage; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics / Q000473:pathology; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D012150:Polymorphism, Restriction Fragment Length; D000071156:Promyelocytic Leukemia Protein; D018168:Receptors, Retinoic Acid / Q000235:genetics; D012016:Reference Values; D012091:Repetitive Sequences, Nucleic Acid; D000072482:Retinoic Acid Receptor alpha; D017384:Sequence Deletion; D014157:Transcription Factors / Q000235:genetics*; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins
chemical_list: D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; C000607071:RARA protein, human; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C070576:PML protein, human; C044171:endodeoxyribonuclease BSSHII; D015252:Deoxyribonucleases, Type II Site-Specific