Small marker X chromosomes lack the X inactivation center: implications for karyotype/phenotype correlations.
The abnormal phenotype and/or mental retardation seen in persons with small marker X (mar(X)) chromosomes has been hypothesized to be due to the loss of the X inactivation center (XIC) at Xq13.2, resulting in two active copies of genes in the pericentromeric region. In order to define precisely the DNA content of mar(X) chromosomes and to correlate phenotype with karyotype, we studied small mar(X) chromosomes, using FISH with probes in the juxtacentromeric region. One of the probes was a 40-kb genomic cosmid for the XIST gene, which maps to the smallest interval known to contain the XIC and is thought to be involved in X inactivation. Our findings reveal that small mar(X) chromosomes do not include the XIC and therefore cannot be subject to X inactivation, supporting the premise that abnormal dosage of expressed genes in the pericentromeric region of the X generates the aberrant phenotype seen in patients with small mar(X) chromosomes.
Department of Genetics and Center for Human Genetics, Case Western Reserve University, Cleveland, OH 44106.
D J
DJ
Wolff
C J
CJ
Brown
S
S
Schwartz
A M
AM
Duncan
U
U
Surti
H F
HF
Willard
D000328:Adult; D002503:Centromere / Q000648:ultrastructure; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations / Q000235:genetics*; D025063:Chromosome Disorders; D002874:Chromosome Mapping; D004303:Dosage Compensation, Genetic; D005260:Female; D017353:Gene Deletion; D005819:Genetic Markers; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008607:Intellectual Disability / Q000235:genetics*; D007621:Karyotyping; D008297:Male; D009030:Mosaicism; D010641:Phenotype; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D012303:Ring Chromosomes; D016615:Telomere; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D014960:X Chromosome / Q000648:ultrastructure*
D005819:Genetic Markers; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D014157:Transcription Factors; C077885:XIST non-coding RNA