Polydactyly is one of the most common congenital limb dysplasia in many animal species. Although preaxial polydactyly (PPD) has been comprehensively studied in humans as a common abnormality, the genetic variations in other animal species have not been fully understood. Herein, we focused on the pig, as an even-toed ungulate mammal model with its unique advantages in medical and genetic researches, two PPD families consisting of four affected and 20 normal individuals were sequenced. Our results showed that the PPD in the sampled pigs were not related to previously reported variants. A strong association was identified at ABCC4 and it encodes a transmembrane protein involved in ciliogenesis. We found that the affected and normal individuals were highly differentiated at ABCC4, and all the PPD individuals shared long haplotype stretches as compared with the unaffected individuals. A highly differentiated missense mutation (I85T) in ABCC4 was observed at a residue from a transmembrane domain highly conserved among a variety of organisms. This study reports ABCC4 as a new candidate gene and identifies a missense mutation for PPD in pigs. Our results illustrate a putative role of ciliogenesis process in PPD, coinciding with an earlier observation of ciliogenesis abnormality resulting in pseudo-thumb development in pandas. These results expand our knowledge on the genetic variations underlying PPD in animals.

中文翻译：

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全基因组重测序揭示了ABCC4变体与猪前轴多指的关联

多指是许多动物中最常见的先天性肢体发育不良之一。尽管人们已对轴前多指畸形（PPD）作为一种普遍的异常进行了全面的研究，但尚未充分了解其他动物物种的遗传变异。在此，我们将重点放在猪上，将其作为在医学和遗传研究中具有独特优势的，有蹄类的有蹄类哺乳动物模型，对由四个受影响的个体和20个正常个体组成的两个PPD家族进行测序。我们的结果表明，采样猪中的PPD与先前报道的变体无关。在ABCC4处鉴定到强关联，并且它编码参与纤毛发生的跨膜蛋白。我们发现，受影响的人和正常人在ABCC4处高度分化，与未受影响的个体相比，所有PPD个体均具有较长的单倍型延伸。在来自多种生物之间高度保守的跨膜结构域的残基处观察到ABCC4中的高分化错义突变（I85T）。这项研究报告ABCC4是新的候选基因，并鉴定了猪PPD的错义突变。我们的结果说明了PPD中纤毛发生过程的推定作用，与早期观察到的纤毛发生异常导致熊猫的拟拇指发育相吻合。这些结果扩展了我们对动物PPD潜在遗传变异的认识。这项研究报告ABCC4是新的候选基因，并鉴定了猪PPD的错义突变。我们的结果说明了PPD中纤毛发生过程的推定作用，与早期观察到的纤毛发生异常导致熊猫的拟拇指发育相吻合。这些结果扩展了我们对动物PPD潜在遗传变异的认识。这项研究报告ABCC4是新的候选基因，并鉴定了猪PPD的错义突变。我们的结果说明了PPD中纤毛发生过程的推定作用，与早期观察到的纤毛发生异常导致熊猫的拟拇指发育相吻合。这些结果扩展了我们对动物PPD潜在遗传变异的认识。