Noriaki Mitsuda

Low density lipoprotein receptor-related protein gene polymorphisms and risk for late-onset Alzheimer's disease in a Japanese population

Low density lipoprotein (LDL) receptor‐related protein (LRP) gene polymorphisms located in the 5′ region and in exon 3, and the apolipoprotein E (APOE) genotype were determined in 100 Japanese patients affected by late‐onset Alzheimers disease (AD). We matched 246 controls for age and found no association between the polymorphism located in the 5′ region of the LRP gene. The distribution of LRP exon 3 genotypes and alleles did not differ between AD and the control groups. However, the frequency of T allele in the Alzheimers group having APOE‐ɛ4 was lower than that in the control group having APOE‐ɛ4, but it was only marginally significant (p=0.022). Age of onset was significantly younger in the patients with CC genotype than those carrying the T allele (p=0.03), and this trend was more evident among non‐APOE‐ɛ4 carriers (p=0.008). These results support the possibility that ApoE and LRP may contribute to the development of AD.

Isolation and mapping of microsatellites from a library microdissected from the Werner syndrome region, 8p11.2–p22

SummaryWe have constructed a new genetic linkage map of the Werner syndrome (WRN) region, using microsatellites from a library which was developed by a chromosome microdissection and enzymatic amplification method. These microsatellites were used to genotype members of CEPH families using a simplified detection system of polymerase chain reaction (PCR) products. Two-point analysis was used to assign 4 microsatellite markers relative to each marker and other markers reported in the CEPH public data base. We confirmed that these 4 markers are located to the WRN region, 8p11.2–p22. Such microsatellites microdissected from the definite chromosome region may be useful for positional cloning.

Dinucleotide repeat polymorphism at the D8S1053

SummaryA polymorphic dinucleotide (CA) repeat clone isolated from a chromosome microdissection library was mapped to chromosome 8p22-p23.1 using human-mouse cell hybrids and linkage anyalysis of 5 CEPH families.

Molecular and epidemiological studies of Werner syndrome in the Japanese population

Werner syndrome (WS) is an autosomal recessive genetic disease characterized by many age-related features. The gene responsible for WS (WRN) has been isolated and contains a helicase domain, but its function is unknown. Six different mutations throughout the WRN gene have been reported in the Japanese population. We have studied whether patients with a specific mutation exhibit distinct phenotypes from others. Fourteen patients with different mutations showed almost the same signs and symptoms and, therefore, the C terminal part of the product appears to be crucial for its functions, although other parts may be important as well. Haplotype analyses using 13 microsatellites covering the 2.8-3.0 cM WRN region showed that two out of six different mutations had founder chromosomes. These two founder chromosomes may be evenly distributed throughout the western part of Japan, suggesting that these mutations go back to a time earlier than 1400 years ago.

Carrier Detection of Werner′s Syndrome Using a Microsatellite That Exhibits Linkage Disequilibrium with the Werner′s Syndrome Locus

SummaryWerners syndrome (WS) is a rare autosomal recessive disorder, one of the progeroid syndromes, characterized by features of premature aging. The genetic defect in WS is unknown but recently the genetic linkage of WS to several markers on the short arm of chromosome 8 has been reported. Genetic analysis of 25 families with WS demonstrated that D8S339 was the closest marker linked to the gene locus for Werners syndrome (WRN), with a peak lod score of 18.29 at recombination frequency 0.001, and showed a linkage disequilibrium with the WRN locus. We studied two unrelated families with WS using ANK1, D8S339, and D8S360. The mutative haplotype identified through the generations in pedigrees provides a means of carrier detection and presymptomatic diagnosis.

Six dinucleotide repeat polymorphisms on chromosome 7.

SummarySix polymorphic dinucleotide (CA) repeat clones isolated from a chromosome microdissection library were mapped to chromosome 7 using human-mouse cell hybrids and linkage analysis of 5 CEPH families.

Dinucleotide repeat polymorphism at the D8S1055

SummaryA polymorphic dinucleotide (CA) repeat clone isolated from a chromosome microdissection library was mapped to chromosome 8p11.2-p12 using human-mouse cell hybrids and linkage analysis of 5 CEPH families.

THREE DINUCLEOTIDE REPEAT POLYMORPHISMS AT THE D8S1217, D8S1220, AND D8S1221 LOCI

AbstractThree polymorphic dinucleotide (CA) repeat clones were isolated from a CEPH mega-YAC clone (936F7), and were localized to chromosome 8 using a panel of 13 mouse/human somatic cell hybrids.

DINUCLEOTIDE REPEAT POLYMORPHISM AT THE D8S1223 LOCUS

SummaryA polymorphic dinucleotide (CA) repeat clone was isolated from a CEPH mega-YAC clone (936F7), and was localized to chromosome 8 using a panel of 13 mouse/human somatic cell hybrids.

DINUCLEOTIDE REPEAT POLYMORPHISM AT THE D8S1054

SummaryA polymorphic CA repeat was isolated from a chromosome microdissection library and was mapped to chromosome 8q11.23-q21.3 using human-mouse cell hybrids and linkage analysis.