Genetic Description of Factor XI Deficiency in Holstein Semen in Western Japan

Abstract

Factor XI deficiency was detected in Holstein cows and mummified foetuses in Japan; however, no report is available about the occurrence of Factor XI deficiency in Holstein semen in Japan. Five hundred cows in twelve dairy farms in Hiroshima Prefecture, Japan were under the study. Genomic DNA was extracted from the cows using a commercial DNA kits and screened to Factor XI mutation. Based on the information of the carrier cows found in the cattle population, four Holstein bulls were analysed for Factor XI mutation. DNA was extracted from bull's semen using phenol chloroform method. Extracted genomic DNA of the bull's semen was typed for Factor XI using specific polymerase chain reaction (PCR) primers. The resultant PCR was sequenced using big dye terminator sequencing method. The pedigree of the bulls was investigated. Furthermore, the inheritance of Factor XI mutation to next generation was estimated. Out of the 500 cows, five were heterozygous to Factor XI. Moreover, out of the four bulls, one was found to carry the mutation of Factor XI; it was also a complex vertebral malformation (CVM) carrier. In DNA sequencing, the insertion mutation of 76 bp of poly-adenine that characterizes the Factor XI deficiency was detected in the carrier bull as well as the carrier cows. Pedigree analysis of the carrier bull revealed that his father and mother ID were 2247419A and 14189172A, respectively, that originated from USA Holstein. Out of six daughter cows born to the carrier bull, one cow (16.6%) inherited Factor XI mutation, while three of them (50.0%) inherited CVM mutation. Autosomal recessive genes that affect cow's reproduction have a particular concern to dairy industry. To our knowledge this is the first report of Factor XI mutation in Holstein semen in Japan.

Factor XI deficiency in animal models

“…In contrast, the opossum genome has two distinct genes for both FXI and plasma kallikrein, indicating that the gene duplication event leading to separate factors occurred early in mammalian evolution [22]. Most probably due to inbreeding, FXI deficiency is found in some cattle [52–54], dogs [55], and cats [56,57]. Surprisingly, and in contrast to mice and most FXI deficient humans, some of these animals suffer from abnormal bleeding showing that the precise role of FXI for hemostasis and thrombosis in vivo still needs to be investigated further.…”