Puech A, Ahnine L, Lüdecke H J, Senger G, Ivens A, Jeanpierre C, Little P, Horsthemke B, Claussen U, Jones C
INSERM U73, Château de Longchamp, Paris, France.
Genomics. 1992 Aug;13(4):1274-80. doi: 10.1016/0888-7543(92)90046-u.
Constitutional and somatic chromosomal abnormalities of the chromosome 11p15 region are involved in an overgrowth malformation syndrome, the Beckwith-Wiedemann syndrome (BWS), and in several types of associated tumors. The bias in parental origin for the different etiologic forms of this syndrome and for loss of heterozygosity in the tumors suggests that a gene (or genes) mapping to this region undergoes genomic imprinting. However, the precise localization of the locus (or loci) for the BWS and associated tumors is still unknown and more markers are required. We therefore isolated 11p15 markers from two libraries: the first one obtained by microdissection of the chromosome 11p15.5 region and the second one, a phage library, constructed from a hybrid cell line containing this region as its sole human DNA. Of 19 microclones isolated from the microdissection library, 11 were evolutionarily conserved. Four phage clones were isolated; one (D11S774) detected a highly informative variable number of tandem repeats (VNTR) and another (D11S773) a biallelic polymorphism. These clones were sublocalized using a panel of somatic cell hybrids that defines eight physical intervals in 11p15.5. Twenty-one clones map to the distal interval that harbors the BWS locus.
11号染色体p15区域的体质性和体细胞染色体异常与一种过度生长畸形综合征——贝克威思-维德曼综合征（BWS）以及几种相关肿瘤有关。该综合征不同病因形式以及肿瘤中杂合性缺失的亲本来源偏向性表明，定位于此区域的一个（或多个）基因会发生基因组印记。然而，BWS及相关肿瘤的基因座（或多个基因座）的确切定位仍不清楚，还需要更多的标记物。因此，我们从两个文库中分离出了11p15标记物：第一个文库是通过对11号染色体p15.5区域进行显微切割获得的，第二个文库是一个噬菌体文库，由一个仅含有该区域作为其唯一人类DNA的杂交细胞系构建而成。从显微切割文库中分离出的19个微克隆中，有11个在进化上是保守的。分离出了4个噬菌体克隆；其中一个（D11S774）检测到一个信息丰富的串联重复可变数目（VNTR），另一个（D11S773）检测到一个双等位基因多态性。使用一组体细胞杂种对这些克隆进行了亚定位，这些杂种定义了11p15.5中的8个物理区间。21个克隆定位于包含BWS基因座的远端区间。
