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

Abstract

An inheritable bleeding disorder with light coat color caused by an autosomal recessive gene has been reported in a population of Japanese black cattle. The disease has been diagnosed as Chediak-Higashi Syndrome (CHS) of cattle which correspond to a human inheritable disorder caused by mutation in LYST gene. To characterize the molecular lesion causing CHS in cattle, cDNAs encoding bovine LYST were isolated from a bovine brain cDNA library. The nucleotide 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 identify the mutation within the LYST gene causing CHS in cattle, cDNA fragments of the LYST gene were amplified from an affected animal by RT-PCR and their 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. The presence of the substitution was completely corresponding with the occurrence of the CHS phenotype among 105 members of pedigrees of the Japanese black 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.

Population Genomics Reveal Recent Speciation and Rapid Evolutionary Adaptation in Polar Bears

“…Melanosomes, where melanin production occurs, are lysosome-related organelles and have been implicated in the progression of disease associated with Lyst mutation in mice (Trantow et al, 2010). The types and positions of mutations identified in LYST vary widely, but Lyst-mutant phenotypes in cattle, mice, rats and mink are characterized by hypopigmentation, a melanosome defect characterized by light coat colour (Kunieda et al, 1999; Runkel et al, 2006; Gutiérrez-Gil et al, 2007). LYST contains seven polar bear-specific missense substitutions, in contrast to only one in brown bear.…”

Platelet Dysfunction in Chediak-Higashi Syndrome-Affected Cattle.

“…Recently, the gene responsible for CHS has been cloned in humans, mice and Japanese Black cattle [3,28,40]. The gene associated with CHS in these species encodes a novel 400-kDa protein, LYST, which stands for lysosome trafficking regulator.…”

A New Method for Rapid Detection of the Mutant Allele for Chediak-Higashi Syndrome in Japanese Black Cattle

“…In 1999, 2 research groups independently found the Lyst mutation in Japanese Black cattle with CHS as a G to A nucleotide substitution at position 6044, resulting in substitution of the amino acid histidine to arginine [4,15]. Based on these observations, the PCR restriction fragment length polymorphism (PCR-RFLP) method has been established for detection of heterozygous and homozygous mutant alleles [4,15] in Japanese Black cattle, and it is now widely used as a gold standard method for diagnosis in Japan. Although PCR-RFLP analysis is specific, sensitive and reproducible, it is disadvantaged by being a slow process, involving several steps, such as restriction enzyme digestion, electrophoresis and DNA staining, taking more than 180 min to analyze 10 samples in a single sample test.…”

“…After the introduction of PCR-RFLP analysis more than a decade ago [4,15], many animals with heterozygous and homozygous mutant alleles have been excluded from breeding, and therefore, we had initially assumed that heterozygous carriers would have been largely eradicated from the cattle population. However, our findings clearly indicated that some heterozygous dams remained, and that unfortunately they had been used for breeding.…”

“…Sci. 75(9): 1237-1239, 2013 Chediak-Higashi syndrome (CHS) is an autosomal recessive disease caused by mutation of the Lyst gene [2,4,5]. CHS has been reported in many mammalian species including humans, cattle, mice and rats [6,7,9].…”