Cloning of bovine LYST gene and identification of a missense mutation associated with Chediak-Higashi syndrome of cattle

An inheritable bleeding disorder with light coat color caused by an autosom al recessive gene has been reported in a population of Japanese black cattl e. The disease has been diagnosed as Chediak-Higashi Syndrome (CHS) of catt le which correspond to a human inheritable disorder caused by mutation in L YST gene. To characterize the molecular lesion causing CHS in cattle, cDNAs encoding bovine LYST were isolated from a bovine brain cDNA library. The n ucleotide and deduced amino acid sequences of bovine LYST had 89.6 and 90.2 % identity with those of the human LYST gene, respectively. In order to ide ntify the mutation within the LYST gene causing CHS in cattle, cDNA fragmen ts of the LYST gene were amplified from an affected animal by RT-PCR and th eir nucleotide sequences were completely determined. Notably, a nucleotide substitution of A to G transition, resulting in an amino acid substitution of histidine to arginine (H2015R) was identified in the affected animal. Th e presence of the substitution was completely corresponding with the occurr ence of the CHS phenotype among 105 members of pedigrees of the Japanese bl ack cattle and no cattle of other populations had this substitution. These findings strongly suggested that H2015R is the causative mutation in CHS of Japanese black cattle.