Marigo V, Roberts D J, Lee S M, Tsukurov O, Levi T, Gastier J M, Epstein D J, Gilbert D J, Copeland N G, Seidman C E
Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
Genomics. 1995 Jul 1;28(1):44-51. doi: 10.1006/geno.1995.1104.
The hedgehog genes encode signaling molecules that play a role in regulating embryonic morphogenesis. We have cloned and sequenced human cDNA copies of two of these genes, SHH and IHH. The SHH clone includes the full coding sequence and encodes a protein 92.4% identical to its murine homologue. The IHH clone is 89% complete and encodes a protein 94.6% identical to its murine homologue. IHH is expressed in adult kidney and liver. SHH expression was not detected in adult tissues examined; however, it is expressed in fetal intestine, liver, lung, and kidney. SHH mapped to chromosome 7q and IHH to chromosome 2 by PCR with DNA from a panel of rodent-human somatic cell hybrids. To identify the chromosomal location of SHH more precisely, a P1 genomic clone of SHH was isolated. This phage contained a CA repeat sequence tagged site that was used to map SHH relative to a polysyndactyly disease locus, using DNA prepared from affected and unaffected members of a large pedigree. SHH is closely linked, but distinct from the polysyndactyly disease locus at 7q36 (maximum lod score = 4.82, theta = 0.05) tightly linked to the EN2 locus. The murine homologues Shh, Ihh, and Dhh were mapped using (C57BL/6J x Mus spretus)F1 x C57BL/6J interspecific backcross. Shh mapped to a position 0.6 cM distal to En2 and 1.9 cM proximal to Il6 on mouse chromosome 5. This location is closely linked but distinct from the murine limb mutation Hx and syntenic to human chromosome 7q36.
刺猬基因编码在调节胚胎形态发生中起作用的信号分子。我们已经克隆并测序了其中两个基因SHH和IHH的人类cDNA拷贝。SHH克隆包含完整的编码序列，编码一种与小鼠同源物有92.4%同一性的蛋白质。IHH克隆完成了89%，编码一种与小鼠同源物有94.6%同一性的蛋白质。IHH在成年肾脏和肝脏中表达。在所检测的成年组织中未检测到SHH的表达；然而，它在胎儿的肠、肝脏、肺和肾脏中表达。通过使用一组啮齿动物-人类体细胞杂种的DNA进行PCR，SHH定位于7号染色体q臂，IHH定位于2号染色体。为了更精确地确定SHH的染色体位置，分离出了SHH的一个P1基因组克隆。这个噬菌体包含一个CA重复序列标签位点，利用从一个大家系的患病和未患病成员制备的DNA，该位点被用于相对于一个多指畸形疾病位点来定位SHH。SHH紧密连锁，但与7q36处的多指畸形疾病位点不同（最大连锁优势分数=4.82，重组率=0.05），该疾病位点与EN2位点紧密连锁。使用（C57BL/6J×小家鼠）F1×C57BL/6J种间回交对小鼠同源物Shh、Ihh和Dhh进行定位。Shh定位于小鼠5号染色体上En2远端0.6 cM和Il6近端1.9 cM的位置。这个位置紧密连锁但与小鼠肢体突变Hx不同，并且与人类7号染色体q36同线。
