Cytogenetic and molecular studies on a recombinant human X chromosome: implications for the spreading of X chromosome inactivation

Journal Article · Wed Jul 01 00:00:00 EDT 1987 · Proc. Natl. Acad. Sci. U.S.A.; (United States)

DOI:https://doi.org/10.1073/pnas.84.14.4954· OSTI ID:5239125

Mohandas, T; Geller, R L; Yen, P H; Rosendorff, J; Bernstein, R; Yoshida, A; Shapiro, L J

A pericentric inversion of human X chromosome and a recombinant X chromosome (rec(X)) derived from crossing-over within the inversion was identified in a family. The rec(X) had a duplication of the segment Xq26.3 ..-->.. Xqter and a deletion of Xp22.3 ..-->.. Xpter and was interpreted to be Xqter ..-->.. Xq26.3::Xp22.3 ..-->.. Xqter. To characterize the rec(X) chromosome, dosage blots were done on genomic DNA from carriers of this rearranged X chromosome using a number of X chromosome probes. Results showed that anonymous sequences from the distal end of the long arm to which probes 4D8, Hx120A, DX13, and St14 bind as well as the locus for glucose-6-phosphate dehydrogenase (G6PD) wee duplicated on the rec(X). Mouse-human cell hybrids were constructed that retained the rec(X) in the active or inactive state. Analyses of these hybrid clones for markers from the distal short arm of the X chromosome showed that the rec(X) retained the loci for steroid sulfatase (STS) and the cell surface antigen 12E7 (MIC2); but not the pseudoautosomal sequence 113D. These molecular studies confirm that the rec(X) is a duplication-deficiency chromosome as expected. In the inactive state in cell hybrids, STS and MIC2 (which usually escape X chromosome inactivation) were expressed from the rec(X), whereas G6PD was not. Therefore, in the rec(X) X chromosome inactivation has spread through STS and MIC2 leaving these loci unaffected and has inactivated G6PD in the absence of an inactivation center in the q26.3 ..-->.. qter region of the human X chromosome. The mechanism of spreading of inactivation appears to operate in a sequence-specific fashion. Alternatively, STS and MIC2 may have undergone inactivation initially but could not be maintained in an inactive state.

• Research Organization: Univ. of California, Torrance (USA)
• OSTI ID: 5239125
• Journal Information: Proc. Natl. Acad. Sci. U.S.A.; (United States), Vol. 84:14
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
CHROMOSOMAL ABERRATIONS
MOLECULAR STRUCTURE
X CHROMOSOME
CROSSING-OVER
INACTIVATION
DNA
HYBRIDIZATION
MAN
MICE
PHOSPHORUS 32
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
CHROMOSOMES
DAYS LIVING RADIOISOTOPES
HETEROCHROMOSOMES
ISOTOPES
LIGHT NUCLEI
MAMMALS
MUTATIONS
NUCLEI
NUCLEIC ACIDS
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
PHOSPHORUS ISOTOPES
PRIMATES
RADIOISOTOPES
RODENTS
VERTEBRATES
550401* - Genetics- Tracer Techniques