T. Ohta et al., THE ORIGIN OF CYTOLOGICALLY UNIDENTIFIABLE CHROMOSOME-ABNORMALITIES -6 CASES ASCERTAINED BY TARGETED CHROMOSOME-BAND PAINTING, Human genetics, 92(1), 1993, pp. 1-5
De novo chromosome structural abnormalities cannot always be diagnosed
by the use of standard cytogenetic techniques. We applied a previousl
y developed chromosome-band-specific painting method to the diagnosis
of such rearrangements. The diagnostic procedures consisted of microdi
ssection of an aberrant chromosomal region of a given patient, polymer
ase chain reaction (PCR) amplification of the dissected chromosomal DN
A, and subsequent competitive fluorescence in situ hybridization (FISH
) using the PCR products as a probe pool on metaphase chromosomes from
the patient and/or a karyotypically normal person. With this strategy
, we studied 6 de novo rearrangements (6p+, 6q+, 9p+, 17p+, +mar, and
+mar) in 6 patients. These rearrangements had been seen by conventiona
l banding but their origin could not be identified. In all 6 patients,
we successfully ascertained the origin. Using an aberrant region-spec
ific probe pool, FISH signals appeared on both the aberrant region and
a region of another specific chromosome pair. A reverse probe pool th
at was generated through the microdissection of normal chromosomes at
a candidate region for the origin of the aberration hybridized with bo
th the aberrant and the candidate regions. We thus diagnosed one patie
nt with 17p+ as having trisomy for 14q32-qter, one with 9p+ as having
trisomy for 12pter-p12, one with 6q+ as having a tandem duplication (t
risomy) of a 6q23-q25 segment, one with 6p+ as having a tandem duplica
tion (trisomy) of a 6p23-q21.3 segment, one with a supernumerary metac
entric marker chromosome as having tetrasomy for 18pter-cen, and the l
ast with an additional small marker chromosome as having trisomy for 1
8p11.1 (or p11.2)-q11.2. The present targeted chromosome-band-painting
method provides the simple and rapid preparation of a probe pool for
region-specific FISH, and is useful for the diagnosis of chromosome ab
normalities of unknown origin.