A Line 1 insertion in the Factor IX gene segregates with mild hemophilia B in dogs

详细信息    查看全文

• 作者：MarjoryB. Brooks ; Weikuan Gu ; JenniferL. Barnas ; Jharna Ray and Kunal Ray
• 刊名：Mammalian Genome
• 出版年：2003
• 出版时间：November 2003
• 年：2003
• 卷：14
• 期：11
• 页码：788-795
• 全文大小：249 KB
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Life Sciences
  Cell Biology
  Anatomy
  Zoology
  
• 出版者：Springer New York
• ISSN：1432-1777

文摘

We undertook the biochemical and molecular characterization of hemophilia in a large pedigree of German wirehaired pointers. Males affected with hemophilia B had approximately 5% normal Factor IX coagulant activity and a proportional reduction of Factor IX protein concentration, indicative of a mild hemophilia B phenotype. Using Southern blot analyses and PCR amplification of genomic DNA, we discovered a large, 1.5-kb insertion in intron 5 of the Factor IX gene of an affected male. The insert consists of a 5 truncated canine Line-1 followed by an approximately 200-bp 3 poly (A) tract, flanked by a 15-bp direct repeat. The insert can be traced through at least five generations and segregates with the hemophilia B phenotype in this breed. This is the first description of a Factor IX mutation associated with mild hemophilia B in a non-human species and provides evidence for a recent Line-1 insertion event in the canine genome.