Huang Yan Qun, Deng Xue Mei, Du Zhi Qiang, Qiu Xiangpin, Du Xiaohui, Chen Wen, Morisson Mireille, Leroux Sophie, Ponce de Léon F Abel, Da Yang, Li Ning
State Key Laboratory of Biotechnology, China Agricultural University, Beijing, 1000094 China.
Gene. 2006 Jun 7;374:10-8. doi: 10.1016/j.gene.2005.07.047. Epub 2006 May 2.
Polydactyly is a common malformation of vertebrate limbs. Preaxial polydactyly (PPD) has been mapped in human, mouse and chicken to the syntenic region of human 7q36. Lmbr1 was thought as the critical candidate gene for human and mouse PPD. To understand the molecular mechanism underlying chicken polydactyly, we have cloned the open reading frame (ORF) of chicken Lmbr1, which contains 1467 nucleotides. Within this ORF, we found one short and one long splice forms. The short splice form has a complete deletion of exon 4. Six cSNPs were found in the chicken ORF, and two of these cSNPs, G797A and G1255A, lead to amino acid substitutions. However, G797A substitution had no significant association with polydactyly and the G1255A substitution had very low frequency in the population. The T1254C polymorphism in exon 13 was found to be strongly associated with polydactyly. Radiation hybrid mapping of a DNA fragment containing intron 13 of the chicken Lmbr1 assigned the gene to chromosome 2 between MCW071 (a marker within the EN2 gene) and ADL0270, a syntenic region to human 7q36.
多指（趾）畸形是脊椎动物肢体常见的一种畸形。人类、小鼠和鸡的轴前多指（趾）畸形（PPD）已被定位到人类7q36的同线性区域。Lmbr1被认为是人类和小鼠PPD的关键候选基因。为了了解鸡多指（趾）畸形的分子机制，我们克隆了鸡Lmbr1的开放阅读框（ORF），其包含1467个核苷酸。在这个ORF内，我们发现了一种短剪接形式和一种长剪接形式。短剪接形式完全缺失外显子4。在鸡的ORF中发现了6个cSNP，其中两个cSNP，G797A和G1255A，导致氨基酸替换。然而，G797A替换与多指（趾）畸形无显著关联，且G1255A替换在群体中的频率非常低。外显子13中的T1254C多态性被发现与多指（趾）畸形密切相关。对包含鸡Lmbr1内含子13的DNA片段进行辐射杂种定位，将该基因定位到2号染色体上，位于MCW071（EN2基因内的一个标记）和ADL0270之间，这是一个与人类7q36同线性的区域。
