Multiple mutant T alleles cause haploinsufficiency of Brachyury and short tails in Manx cats.
Multiple mutant T alleles cause haploinsufficiency of Brachyury and short tails in Manx cats.
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DOI：
10.1007/s00335-013-9471-1
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发表时间：
2013-10
期刊：
影响因子：
2.5
通讯作者：
Bamshad, Michael J.
中科院分区：
文献类型：
--
作者：
Buckingham, Kati J.;McMillin, Margaret J.;Brassil, Margaret M.;Shively, Kathryn M.;Magnaye, Kevin M.;Cortes, Alejandro;Weinmann, Amy S.;Lyons, Leslie A.;Bamshad, Michael J.
大多数哺乳动物都有尾巴，人类和类人猿是明显的例外。了解影响尾巴发育的机制和进化力量的一种方法是确定影响物种内极端尾巴长度变化的遗传因素。在小鼠中，无尾基因座已被证明是复杂的，有证据表明多个不同的基因和突变对尾长、生育力、胚胎发生、雄性传递率和减数分裂重组具有多效性效应。五个猫品种有异常的尾巴长度表型：美国短尾猫，马恩岛猫，小精灵鲍勃，千岛短尾猫和日本短尾猫。我们对来自美国和马恩岛的马恩岛猫的几个独立谱系的T基因进行了测序，并确定了三个1-bp缺失和一个重复/缺失，每一个都预测会引起移码，导致Brachyury蛋白的羧基末端提前终止和截短。95%具有短尾表型的马恩岛猫为T突变杂合型，突变等位基因似乎在很大程度上具有谱系特异性，在重组分数（Θ）为0.00时，T的最大LOD评分为6.21。一个突变的T等位基因与美国短尾猫和小精灵鲍勃共享;这两个品种最近在美国发展。突变体Brachyury蛋白激活下游靶标转录的能力显著低于野生型蛋白。总的来说，这些结果表明，短尾畸形的单倍不足是家猫可变尾长的一种机制。
Most mammals possess a tail, humans and the Great Apes being notable exceptions. One approach to understanding the mechanisms and evolutionary forces influencing development of a tail is to identify the genetic factors that influence extreme tail length variation within a species. In mice, the Tailless locus has proven to be complex, with evidence of multiple different genes and mutations with pleiotropic effects on tail length, fertility, embryogenesis, male transmission ratio, and meiotic recombination. Five cat breeds have abnormal tail length phenotypes: the American Bobtail, the Manx, the Pixie-Bob, the Kurilian Bobtail, and the Japanese Bobtail. We sequenced the T gene in several independent lineages of Manx cats from both the US and the Isle of Man and identified three 1-bp deletions and one duplication/deletion, each predicted to cause a frameshift that leads to premature termination and truncation of the carboxy terminal end of the Brachyury protein. Ninety-five percent of Manx cats with short-tail phenotypes were heterozygous for T mutations, mutant alleles appeared to be largely lineage-specific, and a maximum LOD score of 6.21 with T was obtained at a recombination fraction (Θ) of 0.00. One mutant T allele was shared with American Bobtails and Pixie-Bobs; both breeds developed more recently in the US. The ability of mutant Brachyury protein to activate transcription of a downstream target was substantially lower than wild-type protein. Collectively, these results suggest that haploinsufficiency of Brachyury is one mechanism underlying variable tail length in domesticated cats.
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