| Research Abstract |
Present study carried out the following projects ;
1. Cloning of holocarboxylase synthetase (HCS) gene
Deficiency of HCS causes biotin-responsive multiple carboxylase. We have choned the human HCScDNA,which shows homology to BirA and maps to chromosome 21q22.1.
2. Mutation studies from various genetic disorders :
1) Mutation analysis in 6 Japanese patients revealed the misssense mutation of T997C,G1935A and one base deletion (G1067). These mutations together account for about 83% of Japanese HCS alleles. 2) Mutations of GSD patients ; R83H,P257L,R170X,g727t and IVS 1nt-a, together account for 98% of Japanese GSD mutant alleles.
The g727t splicing mutation was the most common mutation among the Japanese patients. 3) Mutaions of PKU patients ; R413P,IVS-4nt-1, R111X,Y204C,R243Q,R252W,R241C,R278I and IVS-9, account for 67% of Japanese PKU mutant alleles. 4) Mutaions of PKU patients ; R243Q,R413P,IVS-4, R365X,R111X,R261Q,Y204C,account for 61% of Chinese PKU mutant alleles. 5) Mutations of Japanese methylmalonic acidemia ; G425T and 769DELTACA.6) Mutations of Japanese CPT II deficient Patients ; F352C,V368I and M647V.7) Mutation of Japanese familial ALS ; H46R.
3. Development of multiplex allele specific PCR ; We have applied ASPCR methodology to the detection of mutations in PAH gene. Single ASPCR tests have been developed for 12 mutations found in Japan and China. ASPCR reactions for 3 or 4 mutaions have been multiplexed. The two multiplex tests will detect the presence of the R111X,R261Q and Y204C mutations and the R243Q,R413P,IVS 4nt-1 and Y356X mutations, respectively.
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