02638nas a2200325   4500000000100000008004100001260001300042653002400055653002300079653001900102653002100121653001100142653001000153653001200163653001300175653002500188653003600213653002200249100001000271700001300281700001500294700001500309700001300324700001300337245011700350300001000467490000700477520181400484022001402298       2013                            d  c2013 Oct10aAntigens, Bacterial10aAsia, Southeastern10aDNA, Bacterial10aGenes, Bacterial10aHumans10aJapan10aleprosy10aMutation10aMycobacterium leprae10aPolymorphism, Single Nucleotide10aRepublic of Korea1 aKai M1 aNakata N1 aMatsuoka M1 aSekizuka T1 aKuroda M1 aMakino M00aCharacteristic mutations found in the ML0411 gene of Mycobacterium leprae isolated in Northeast Asian countries.  a200-40 v193 a<p>Genome analysis of Mycobacterium leprae strain Kyoto-2 in this study revealed characteristic nucleotide substitutions in gene ML0411, compared to the reference genome M. leprae strain TN. The ML0411 gene of Kyoto-2 had six SNPs compared to that of TN. All SNPs in ML0411 were non-synonymous mutations that result in amino acid replacements. In addition, a seventh SNP was found 41 bp upstream of the start codon in the regulatory region. The seven SNP sites in the ML0411 region were investigated by sequencing in 36 M. leprae isolates from the Leprosy Research Center in Japan. The SNP pattern in 14 of the 36 isolates showed similarity to that of Kyoto-2. Determination of the standard SNP types within the 36 stocked isolates revealed that almost all of the Japanese strains belonged to SNP type III, with nucleotide substitutions at position 14676, 164275, and 2935685 of the M. leprae TN genome. The geographical distribution pattern of east Asian M. leprae isolates by discrimination of ML0411 SNPs was investigated and interestingly turned out to be similar to that of tandem repeat numbers of GACATC in the rpoT gene (3 copies or 4 copies), which has been established as a tool for M. leprae genotyping. All seven Korean M. leprae isolates examined in this study, as well as those derived from Honshu Island of Japan, showed 4 copies of the 6-base tandem repeat plus the ML0411 SNPs observed in M. leprae Kyoto-2. They are termed Northeast Asian (NA) strain of M. leprae. On the other hand, many of isolates derived from the Okinawa Islands of Japan and from the Philippines showed 3 copies of the 6-base tandem repeat in addition to the M. leprae TN ML0411 type of SNPs. These results demonstrate the existence of M. leprae strains in Northeast Asian region having characteristic SNP patterns.</p>  a1567-7257