title: Isolation of a cosmid clone corresponding to an inv(21) breakpoint of a patient with transient abnormal myelopoiesis.
abstract: Transient abnormal myelopoiesis (TAM) is a leukemoid reaction occurring occasionally on Down syndrome (DS) newborn infants. It has been hypothesized that "disomic homozygosity" in 21-trisomic cells plays an important role in the genesis of TAM, and the putative TAM gene was suggested to be mapped at a 21q11 region. We encountered a DS-associated TAM infant with a 47,XY,inv(21)(q11.1q22.13),+inv(21)(q11.1q22.13) karyotype. On the basis of another presumption that in this patient the putative TAM gene is disrupted by the break, we tried to isolate a breakpoint DNA. FISH analysis with cosmid clones corresponding to various sequence-tagged-site (STS) markers mapped at around 21q11.1-q11.2, we confirmed that the proximal breakpoint of the inv(21) was located between two STSs, G51E07 and D21S215, the latter locus being consistent with the previous tentative mapping. After construction of a cosmid contig encompassing between the two markers, we have isolated a cosmid clone corresponding to the proximal breakpoint of the inversion. This breakpoint was located near a previously identified duplicated region that is homologous to the sequence at 21q22.1. The isolated cosmid clone is useful for analysis of other TAM patients and for a search for a transcript at or flanking the breakpoint.
authors.affiliation: Department of Human Genetics, Nagasaki University School of Medicine, Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Ohta
authors.forename: M
authors.initials: M
authors.lastname: Nakano
authors.forename: T
authors.initials: T
authors.lastname: Tsujita
authors.forename: K
authors.initials: K
authors.lastname: Abe
authors.forename: K
authors.initials: K
authors.lastname: Osoegawa
authors.forename: T
authors.initials: T
authors.lastname: Yamagata
authors.forename: K
authors.initials: K
authors.lastname: Yoshiura
authors.forename: Y
authors.initials: Y
authors.lastname: Jinno
authors.forename: E
authors.initials: E
authors.lastname: Soeda
authors.forename: Y
authors.initials: Y
authors.lastname: Nakamura
authors.forename: N
authors.initials: N
authors.lastname: Niikawa
mesh_terms: D000328:Adult; D001483:Base Sequence; D007446:Chromosome Inversion; D016386:Chromosome Walking; D002891:Chromosomes, Human, Pair 21; D003001:Cloning, Molecular / Q000379:methods*; D003360:Cosmids / Q000235:genetics; D004314:Down Syndrome / Q000150:complications; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008969:Molecular Sequence Data; D009196:Myeloproliferative Disorders / Q000150:complications / Q000235:genetics*; D016324:Sequence Tagged Sites