Nonrandom X chromosome DNA methylation patterns in hemophiliac females.
Open Access
- 1 April 1989
- journal article
- research article
- Published by American Society for Clinical Investigation in Journal of Clinical Investigation
- Vol. 83 (4) , 1400-1403
- https://doi.org/10.1172/jci114028
Abstract
Molecular X chromosome inactivation analysis was used to characterize three females (and their families) with severe hemophilia. First, the maternal and paternal X chromosomes were distinguished by restriction fragment length polymorphisms (RFLPs). Second, the patterns of methylation of X chromosome genes using methylation-sensitive restriction endonucleases were determined. Of the six X chromosome probes tested, only the phosphoglycerol-kinase (PGK) and hypoxanthine-phosphoribosyl-transferase (HPRT) clones were informative, indicating that other X chromosome probes are not useful for X inactivation analysis. After digestion with Hpa II or Hha I, the hybridization intensity of the RFLPs of all three mothers and an unaffected sister were diminished by 50%, consistent with random X chromosome inactivation. The methylation patterns of the X chromosomes of the affected females, however, were clearly nonrandom. Depending upon the probe and the patient, HPRT and PGK sequences were either completely methylated or unmethylated. These findings are extremely suggestive that nonrandom X chromosome inactivation (lyonization) is the basis for severe hemophilia in these females.Keywords
This publication has 22 references indexed in Scilit:
- Inheritance of allelic blueprints for methylation patternsCell, 1988
- DNA methylation and gene activityCell, 1988
- Allele-specific methylation of the human c-Ha-ras-1 geneCell, 1987
- Genomic imprinting determines methylation of parental alleles in transgenic miceNature, 1987
- Carrier Detection in X-Linked Agammaglobulinemia by Analysis of X-Chromosome InactivationNew England Journal of Medicine, 1987
- The Molecular Basis of Severe Hemophilia B in a GirlNew England Journal of Medicine, 1986
- CpG-rich islands and the function of DNA methylationNature, 1986
- Genetic Screening for Hemophilia A (Classic Hemophilia) with a Polymorphic DNA ProbeNew England Journal of Medicine, 1985
- Sequence of the promoter region of the gene for human X-linked 3-phosphoglycerate kinaseGene, 1984
- A CLINICALLY USEFUL DNA PROBE CLOSELY LINKED TO HAEMOPHILIA AThe Lancet, 1984