Chung W K, Power-Kehoe L, Chua M, Leibel R L
Laboratory of Human Behavior and Metabolism, The Rockefeller University, New York, New York.
Genome Res. 1996 May;6(5):431-8. doi: 10.1101/gr.6.5.431.
As part of an effort to identify informative molecular markers for genetic analysis of human pedigrees segregating for obesity, we have developed a genetic map of human 1p in the region of the OB receptor (OBR), the gene that is defective in murine diabetes (Obrdb) and rat Zucker fatty (Obrfa) mutations located on mid-chromosome 4 and chromosome 5, respectively. OBR was mapped 0.9 cR centromeric to WI-9515 and 2.2 cR telomeric of WI-7249 by radiation hybrid (RH) mapping. Ten yeast artificial chromosomes (YACs) containing OBR were identified, confirming the location of OBR centromeric to WI-9515 and telomeric to WI-7249. Additionally, five P1 artificial chromosomes (PACs) were identified that comprised a contiguous series of overlapping clones spanning the length of OBR. WI-5182 was contained within the two PACs that are 3' of OBR. Using a panel of 68 individuals from a single three-generation family and an additional nuclear family, we have mapped 18 polymorphic markers including phosphoglucomutase 1 (PGM1), which is centromeric to Obrdb / Obrfa, and D1S85, which is telomeric to Obrdb / Obrfa in the mouse and rat. The following composite map integrates these radiation hybrid, genetic, and physical maps: Centromere-@WI-7249-[OBR; WI-5182]-D1S198-[WI-9515; WI-6550; D1S2866]-D1S2825-[WI-3077; D1S2886]-[D1S515; DS1613; PGM1]-[D1S312; D1S473; D1S230; D1S246; D1S203]-D2S1643-[D1S1669; D1S1596;]UNCJ-D1S476- D1S85-D1S220-C8B-GTAT1A7. Unresolvable markers are within brackets. A comparison of gene order on mouse chromosome 4, rat chromosome 5, and human 1p indicates that between rodents and humans, there has been a rearrangement of the gene order in the region surrounding OBR.
作为为分离肥胖症的人类家系进行遗传分析确定信息性分子标记工作的一部分，我们绘制了人类1号染色体上位于OB受体（OBR）区域的遗传图谱，该基因在小鼠糖尿病（Obrdb）和大鼠Zucker肥胖（Obrfa）突变中存在缺陷，这些突变分别位于小鼠4号染色体中部和大鼠5号染色体上。通过辐射杂种（RH）图谱分析，将OBR定位在WI-9515着丝粒侧0.9厘摩处以及WI-7249端粒侧2.2厘摩处。鉴定出了10个包含OBR的酵母人工染色体（YAC），证实了OBR位于WI-9515着丝粒侧和WI-7249端粒侧的位置。此外，还鉴定出了5个P1人工染色体（PAC），它们构成了一系列连续重叠的克隆，覆盖了OBR的全长。WI-5182包含在OBR 3'端的两个PAC中。使用来自一个三代家系的68个个体以及另一个核心家系组成的样本，我们绘制了18个多态性标记的图谱，包括磷酸葡萄糖变位酶1（PGM1），它位于Obrdb / Obrfa着丝粒侧，以及D1S85，它在小鼠和大鼠中位于Obrdb / Obrfa端粒侧。以下复合图谱整合了这些辐射杂种图谱、遗传图谱和物理图谱：着丝粒 - @WI-7249 - [OBR; WI-5182] - D1S198 - [WI-9515; WI-6550; D1S2866] - D1S2825 - [WI-3077; D1S2886] - [D1S515; DS1613; PGM1] - [D1S312; D1S473; D1S230; D1S246; D1S203] - D2S1643 - [D1S1669; D1S1596;]UNCJ - D1S476 - D1S85 - D1S220 - C8B - GTAT1A7。无法解析的标记在方括号内。小鼠4号染色体、大鼠5号染色体和人类1号染色体上基因顺序的比较表明，在啮齿动物和人类之间，OBR周围区域的基因顺序发生了重排。
