Application of human-pig genetic comparative mapping to pediatric surgical disease

人猪遗传比较图谱在小儿外科疾病中的应用

• 批准号: 09671208
• 负责人: HORI Tetsuo
• 金额: $ 1.73万
• 依托单位: University of Tsukuba, Institute of clinical medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09671208/
• 关键词: ANAL ATRESIA; comparative map; gene; human; pig; pediatric surgery; pig; 鎮肛; ヒト; 比較遺伝子マップ

Anal Atresia (AA) is a fairly common malformation in the new-born human ; the incidence is about 1/5,000. A strikingly similar malformation occurs also in piglets ; incidence estimated at 9/5,000 in Ibaraki prefecture, Japan. A line of pigs with a very high AA incidence has been established by selective breeding. The affected animals used for breeding were derived from Landrace or Large White populations in Japan and were treated surgically soon after birth. Crossing affected parents increased the incidence from 30% (1983-1987) to presently 62%. Embryological studies have shown that the cause of this malformation is a defect of the dorsal cloacal plate during the development of the cloaca (Ikebukuro et al., 1994 Pediatr Surg Int. 9, 2). Previous segregation analysis in this closed population suggested that porcine AA is controlled by two major loci, one autosomal recessive and one autosomal dominant (Ohkawa et al., 1985 Teratology 32 : 46B).We have generated a backcross pedigree by mating an affected female to an unaffected male from the Meishan breed in order to further investigate the genetic basis for this malformation. F_1 animals were backcrossed to affected animals from the AA line. None out of 39 F1 animals exhibited AA suggesting that at least one causative mutation is recessive, In the backcross, 29 out of 315 offspring were affected. The results of a genome scan using microsatellite markers is reported. A genome scan using only affected progeny have been initiated. So far suggestive linkage has been obtained for one chromosomal region and additional data are currently collected to confirm or reject linkage.

肛门闭锁（Anal Atresia，AA）是新生儿中较为常见的一种畸形，发病率约为1/5000。在仔猪中也发生一种惊人相似的畸形;在日本茨木县，发病率估计为9/5，000。通过选择性育种建立了AA发病率非常高的猪系。用于育种的受影响动物来自日本的长白猪或大型白色种群，出生后立即进行手术治疗。杂交受影响的父母增加发病率从30%（1983-1987年）到目前的62%。胚胎学研究表明，这种畸形的原因是泄殖腔发育过程中泄殖腔背板的缺陷（Ikebukuro等人，1994 Pediatr Surg Int. 9，2）。先前在该封闭群体中的分离分析表明，猪AA受两个主要基因座控制，一个是常染色体隐性基因座，一个是常染色体显性基因座（Ohkawa et al.，1985 Teratology 32：46 B）。我们通过将梅山品种的一只患病雌性与一只未患病雄性交配产生了一个回交谱系，以进一步研究这种畸形的遗传基础。F_1代动物与AA系的患病动物回交。在39头F1代动物中没有一头表现出AA，表明至少有一个致病突变是隐性的。在回交中，315头后代中有29头受到影响。报告了利用微卫星标记进行基因组扫描的结果。仅使用受影响后代的基因组扫描已经开始。到目前为止，已经获得了一个染色体区域的暗示性连锁，目前正在收集更多的数据来确认或拒绝连锁。

项目成果

T.HORI: "Genetic mapping of genes causing Anal Atresia in the pig" Animal Genetics. 29. 72 (1998)

T.HORI：“引起猪肛门闭锁的基因的遗传图谱”《动物遗传学》。

大川治夫: "鎖肛 (自然発生ブタ)" 小児外科. 29. 211-216 (1997)

Haruo Okawa：“肛门链（自发猪）”小儿外科。 29. 211-216 (1997)

AK Fridolfsson: "Expansion of the pig comparative map by expressed sequence tags (EST) mopping" Mammalian Genome. 8. 907-912 (1997)

AK Fridolfsson：“通过表达序列标签 (EST) 拖曳来扩展猪比较图谱”哺乳动物基因组。

AK Fridolffson: "Expansion of the pig comparative map by expressed sequence tags(EST)mapping" Mammalian Genone. 8. 907-912 (1997)

AK Fridolffson：“通过表达序列标签 (EST) 作图扩展猪比较图谱”哺乳动物基因组。

堀哲夫: "胆管疾患に対する肝移植" 小児内科. 29・12. 1644-1648 (1997)

Tetsuo Hori：“肝移植治疗胆管疾病”小儿内科 1644-1648（1997）。