Porteous D J, Bickmore W, Christie S, Boyd P A, Cranston G, Fletcher J M, Gosden J R, Rout D, Seawright A, Simola K O
Proc Natl Acad Sci U S A. 1987 Aug;84(15):5355-9. doi: 10.1073/pnas.84.15.5355.
We show that chromosome-mediated gene transfer can provide an enriched source of DNA markers for predetermined, subchromosomal regions of the human genome. Forty-four human DNA recombinants isolated from a HRAS1-selected chromosome-mediated gene transformant map exclusively to chromosome 11, with several sublocalizing to the Wilms tumor region at 11p13. We present a detailed molecular map of the deletion chromosomes 11 from five WAGR (Wilms tumor/aniridia/genitourinary abnormalities/mental retardation) syndrome patients, three of which are at the limits of cytogenetic resolution but shown here to be molecularly distinguishable and overlapping. We can define ten distinct regions of the short arm of chromosome 11, five of which subdivide band 11p13. We also map two independent 11p13 translocation breakpoints to within the smallest region of overlap defined by the WAGR deletions. The first comes from a patient with familial aniridia, and the second from a patient with Potter facies and genitourinary dysplasia. The close similarities in map location and affected cell lineage for Wilms tumor and genitourinary dysplasia suggest that they may be alternative manifestations of mutation at the same locus.
我们证明,染色体介导的基因转移可为人类基因组中预先确定的亚染色体区域提供丰富的DNA标记来源。从一个经HRAS1选择的染色体介导的基因转化体中分离出的44个人类DNA重组体仅定位于11号染色体,其中有几个亚定位到11p13的Wilms瘤区域。我们展示了来自5名WAGR(Wilms瘤/无虹膜/泌尿生殖系统异常/智力迟钝)综合征患者的11号缺失染色体的详细分子图谱,其中3名患者处于细胞遗传学分辨率的极限,但在此显示在分子水平上是可区分且有重叠的。我们可以定义11号染色体短臂的10个不同区域,其中5个区域细分了11p13带。我们还将两个独立的11p13易位断点定位到由WAGR缺失定义的最小重叠区域内。第一个来自一名家族性无虹膜患者,第二个来自一名患有Potter面容和泌尿生殖系统发育异常的患者。Wilms瘤和泌尿生殖系统发育异常在图谱位置和受影响细胞谱系方面的密切相似性表明,它们可能是同一基因座突变的不同表现形式。