Wöhlke A, Kuiper H, Distl O, Drögemüller C
Institute of Animal Breeding and Genetics, University of Veterinary Medicine Hannover, Hannover, Germany.
Cytogenet Genome Res. 2006;115(2):123-8. doi: 10.1159/000095231.
The ALX4 (aristaless-like homeobox 4) gene encodes a paired-type homeodomain transcriptional activator and plays a major role in anterior-posterior pattern formation during limb development. Here, the cloning, genomic structure and expression of the bovine ortholog of the ALX4 gene are reported. The bovine ALX4 gene consists of four exons and is located on BTA15q28-->q29 in a region syntenic to HSA11p11.2. The transcribed ALX4 mRNA encodes a 397-amino-acid protein showing a paired-type homeodomain and a C-terminal stretch of amino acids known as the OAR- or aristaless domain. The predicted protein shares 92.5% identity to human and mouse ALX4 proteins and all three species share almost complete identity in the conserved domains. ALX4 expression was detected by reverse transcriptase polymerase chain reaction in bovine fetal limb bones. The ALX4 gene was evaluated as a candidate gene for bovine syndactyly which has been mapped on the telomeric region of cattle chromosome 15. Sequencing of the four exons with flanking sequences of the bovine ALX4 gene from a panel of 14 affected animals belonging to German Holstein, German Fleckvieh and crossbreds, and 27 unaffected individuals from German Holstein revealed five silent SNPs within the coding region out of eleven SNPs in total. Four SNPs were polymorphic in the affected animals, but in comparison to the genotyped unaffected individuals the genotype distribution showed no evidence for an association to the phenotype. Therefore our data indicate that the ALX4 gene can probably be excluded as candidate gene for bovine syndactyly in the examined animals.
ALX4（无触角样同源框4）基因编码一种配对型同源结构域转录激活因子，在肢体发育过程中的前后模式形成中起主要作用。本文报道了牛ALX4基因直系同源物的克隆、基因组结构及表达情况。牛ALX4基因由四个外显子组成，位于牛15号染色体q28→q29区域，该区域与人类11号染色体p11.2区域同线。转录的ALX4 mRNA编码一个397个氨基酸的蛋白质，该蛋白质具有一个配对型同源结构域和一段称为OAR或无触角结构域的C末端氨基酸序列。预测的蛋白质与人类和小鼠的ALX4蛋白质具有92.5%的同一性，并且在保守结构域中这三个物种几乎完全相同。通过逆转录聚合酶链反应在牛胎儿肢体骨骼中检测到了ALX4的表达。ALX4基因被评估为牛并指畸形的候选基因，牛并指畸形已定位在牛15号染色体的端粒区域。对来自德国荷斯坦牛、德国弗莱维赫牛及其杂交后代的14只患病动物以及27只来自德国荷斯坦牛的未患病个体的牛ALX4基因的四个外显子及其侧翼序列进行测序，总共11个单核苷酸多态性（SNP）中，编码区域内发现了5个沉默SNP。其中4个SNP在患病动物中具有多态性，但与基因分型的未患病个体相比，基因型分布没有显示出与表型相关的证据。因此，我们的数据表明，在所检测的动物中，ALX4基因可能可以被排除作为牛并指畸形的候选基因。
