A recessive form of arthrogryposis multiplex congenita (AMC) was detected 20 years ago in the Swiss Large White (SLW) pig population. A diagnostic marker test enabled the identification of carrier animals, but the underlying causal mutation remains unknown. To identify the mutation underlying AMC, we collected SNP chip genotyping data for 11 affected piglets and 23 healthy pigs. Association testing using 47 829 SNPs confirmed that AMC maps to SSC5 (P = 9.4 × 10⁻¹³). Subsequent autozygosity mapping revealed a common 6.06 Mb region (from 66 757 970 to 72 815 151 bp) of extended homozygosity in 11 piglets affected by AMC. Using WGS data, we detected a 63‐bp insertion compatible with the recessive inheritance of AMC in the second exon of KIF21A gene encoding Kinesin Family Member 21A. The 63‐bp insertion is predicted to introduce a premature stop codon in KIF21A gene (p.Val41_Phe42insTer) that truncates 1614 amino acids (~97%) from the protein. We found that this deleterious allele still segregates at a frequency of 0.1% in the SLW pig population. Carrier animals can now be detected unambiguously and excluded from breeding.

中文翻译：

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猪KIF21A基因第2外显子中的63 bp插入与多发性关节炎的先天性有关。

20年前在瑞士大白（SLW）猪种群中发现了隐性形式的多形性先天性关节病（AMC）。诊断标志物测试可以鉴定携带动物，但潜在的因果突变仍然未知。为了识别AMC的潜在突变，我们收集了11头受影响仔猪和23头健康猪的SNP芯片基因分型数据。使用47 829个SNP进行的关联测试确认AMC映射到SSC5（P  = 9.4×10 ^-13）。随后的纯合子作图揭示了受AMC影响的11只仔猪的一个普通的6.06 Mb区域（从66 757 970到72 815 151 bp）延伸的纯合性。使用WGS数据，我们在KIF21A的第二个外显子中检测到与AMC的隐性遗传兼容的63 bp插入编码驱动蛋白家族成员21A的基因。预计63 bp的插入会在KIF21A基因（p.Val41_Phe42insTer）中引入一个过早的终止密码子，该密码子会截断该蛋白质中的1614个氨基酸（〜97％）。我们发现该有害等位基因在SLW猪种群中的分离频率仍为0.1％。现在可以明确地检测出携带动物，并将其排除在繁殖之外。