title: Direct detection of non-random X chromosome inactivation by use of a transcribed polymorphism in the XIST gene.
abstract: As a result of X chromosome inactivation, females are mosaic for cell lineages in which either the paternal or the maternal X chromosome is active, and, if inactivation were random, each lineage should be present at approximately the same frequency. Detection of instances of non-random X inactivation can be important both clinically and for the study of X chromosome inactivation. Identification of a single-base polymorphism in an expressed region of the human XIST gene has permitted the development of a direct PCR-based assay for randomness of X inactivation. Oligonucleotide primers were designed, incorporating the variant base, and conditions established that allowed allele-specific PCR amplification. As the XIST gene is expressed only from the inactive X chromosome, differential amplification of the alleles in cDNA from heterozygotes can be used as an indicator of non-random inactivation. Using this assay, non-random X chromosome inactivation has been demonstrated in chromosomally abnormal cell lines and in lymphocytes from heterozygous, normal females. Virtually complete non-random X inactivation was also shown in a mother and her daughter, suggesting the existence of some familial factor affecting X chromosome inactivation.
authors.affiliation: Department of Genetics, Case Western Reserve University School of Medicine, Cleveland, OH 44106-4955, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: Rupert
authors.forename: C J
authors.initials: CJ
authors.lastname: Brown
authors.forename: H F
authors.initials: HF
authors.lastname: Willard
mesh_terms: D001483:Base Sequence; D002460:Cell Line; D002648:Child; D017931:DNA Primers; D004303:Dosage Compensation, Genetic; D005260:Female; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D011110:Polymorphism, Genetic; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D017931:DNA Primers; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D014157:Transcription Factors; C077885:XIST non-coding RNA