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Mutation associated with factor XI deficiency in Holstein cattle
A deficiency of blood coagulation factor XI is known to occur not only in small animals but also in large animals, especially in Holstein cattle. Recently, a mutation leading to this defect could be discovered - and it might be more common in the USA Holstein sires than previously thought.

An autosomal recessive deficiency of blood coagulation factor XI (FXI) has been described in Holstein cattle.

Current testing methods are unsuitable for accurately identifying carriers (heterozygotes) of the disease.

To identify the molecular basis of this deficiency, a polymerase chain reaction (PCR)-based strategy was implemented to clone and sequence the bovine FXI gene (F11) from animals of different genotypes.
Approximately 14 kb of genomic DNA sequence and 1.8 kb of cDNA sequence, corresponding to exon 3 through the 3`-UTR, of the bovine gene were obtained.

Comparison of sequences derived from homozygous normal and deficient individuals revealed that FXI deficiency in Holsteins is associated with the insertion of a 76 bp segment [AT(A)28TAAAG(A)26GGAAATAATAATTCA] within exon 12.
This insertion introduces a stop codon that results in a mature FXI protein lacking the functional protease domain encoded by exons 13, 14 and 15.

Based on these data, a DNA-based diagnostic test has been developed for accurate genotyping.

Using this method, the frequency of the mutated allele has been determined to be 1.2% in a contemporary population of the USA Holstein sires.



Source: Marron, B. M., Robinson, J. L., Gentry, P. A. & Beever, J. E. (2004): Identification of a mutation associated with factor XI deficiency in Holstein cattle. In: Animal Genetics 35 (6), 454-456.












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