1992 Fiscal Year Final Research Report Summary
DIAGNOSTIC METHODS BY DNA ANALYSIS OF DRIED BLOOD SPOTS AND CLASSIFICATION OF INHERITED DISEASE BY MUTANT GENOTYPES.
| Project/Area Number |
02557041
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| Research Category |
Grant-in-Aid for Developmental Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Pediatrics
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| Research Institution | TOHOKU UNIVERSITY |
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Principal Investigator |
NARISAWA K Tohoku Univ. Sch. of Med. Dept. of Biochem. Genet. PROF., 医学部, 教授 (90004647)
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| Co-Investigator(Kenkyū-buntansha) |
SUZUKI Y Tohoku Univ, Sch, of Med. Dept. of Biochem. Genet. ASSIST. PROF., 医学部, 助手 (80216457)
KURE S Tohoku Univ. Sch. of Med. Dept. of Biochem. Genet. ASSIST. PROF., 医学部, 助手 (10205221)
MATSUBARA Y Tohoku Univ. Sch. of Med. Dept. of Biochem. Genet. ASSOC. PROF., 医学部, 助教授 (00209602)
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| Project Period (FY) |
1990 – 1992
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| Keywords | MOLECULAR GENETICS / GENE CLONING / GENE ANALYSIS / GENETIC DIAGNOSIS / INHERITED DISEASE / 遺伝子診断 |
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| Research Abstract |
1. Medium chain acyl-CoA dehydrogenase(MCAD) deficiency is an autosomal recessive disorder which is known to cause Reye-like syndrome in children and sudden infant death. A point mutation of lysine(329)-to-glutamic acid(329)substitution in the MCAD gene was identified as the most common mutation in patients with MCAD deficiency. This mutation is responsible for about 90% of mutant MCAD alleles in Caucasians and now be detected by DNA diagnostic methods using Guthrie cards. Screening for the mutation among newborns in England, Australia, and United States of America indicates the prevalence of carriers to be 1 of 40-107, suggesting the high incidence of the mutation.
2. Nonketotic hyperglycinemia(NKH) is an autosomal recessive metabolic disorder. We have cloned and characterized a human glycine decarboxylase cDNA responsible for NKH. This clone was 3,705 bp in length and encoded 1,020 amino acids. NKH is a disorder with high incidence in northern Finland. To understand the genetic backgr
… More
ound of this high incidence, we examined the glycine decarboxylase in a typical case of NKH. Structural analysis of glycine decarboxylase mRNA from the patient revealed a single nucleotide substitution from G to T in the protein coding region, which resulted in an amino acid alteration from Ser(564) to Ile(564). The patient was homozygous for this mutation. Furthermore, this mutation was present in 70% of glycine decarboxylase gene alleles in Finnish patients with NKH, whereas it was not found in 20 alleles of non-Finnish patients. The results suggest that this mutation is responsible for the high incidence of NKH in Finland.
3. Phenylketonuria(PKU) is an autosomal recessive disorder caused by a deficiency of the hepatic phenylalanine hydroxylase. We have developed a simple rapid DNA screening test that allows us to analyze seven known PKU mutations in Orientals, This method is based on an allele specific PCR of the genomic DNA extracted from Guthrie cards and provides an easy method of simultaneously analyzing plural mutations. Less
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