Cytognetic and Molecular Genetic Study of Transient Abnormal Myelopoiesis

点击翻译按钮获取中文摘要

Transient abnormal myclopoiesis (TAM) is a leukemoid reaction occurring occasionally in 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. Based on 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 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 to the previous tentative mapping. After construction of a cosmid contig encompassing between the 2 markers, we have isolated a cosmid clone corresponding to the proximal breakpoint of the inversion. This breakpoint was located nearby 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.