http://chineseinput.net/에서 pinyin(병음)방식으로 중국어를 변환할 수 있습니다.
변환된 중국어를 복사하여 사용하시면 됩니다.
- 中文 을 입력하시려면 zhongwen을 입력하시고 space를누르시면됩니다.
- 北京 을 입력하시려면 beijing을 입력하시고 space를 누르시면 됩니다.
RISS 인기검색어
- 검색키워드
- 저자 : Lingyan Shen (검색결과 1 건)
-
Assessment of the PGRN and MAPT mutations in young(<65 years)Korean dementia patients
Lingyan Shen Gachon University Graduate School 2014 국내석사
Frontotemporal dementia (FTD) is the second most common form of early-onset (<65 years of age) neurodegenerative disease after Alzheimer’s disease (AD). At least seven genes have been reported as responsible risk factors for FTD, of which PGRN and MAPT were identified as the main disease-causing genes with 50% of the frequency for FTD, especially for familial FTD. To date, only a few studies of the two genes were performed in Asia, especially in Korea. The aim of this study is to investigate PGRN and MAPT mutations in young Korean dementia patients, and to explore the genetic and clinical features of various neurodegenerative disorders in Korea. PGRN and MAPT were analyzed by direct sequencing for 110 young Korean patients with early onset dementia (89EOAD and 21FTD), followed by single strand conformation polymorphism (SSCP) analyses, web-based splice sites prediction and/or protein function prediction, and in silico prediction and protein modeling. One novel deletion mutation (c.IVS8+23_+26delTGGG), one novel missense mutation (c.1767G>T, Leu589Phe; Leu434Phe and/or Leu409Phe), one novel intronic polymorphism (c.IVS12+56G>C), one common mutation which might be novel in Asia/Korea (rs113219200) and four common mutations (rs9897526, rs850713, rs5848 and rs25646; Asp108) were detected in the PGRN gene. But only two known silent mutations (rs115381139; Asn727 and rs11568305; Pro587) were identified in the MAPT gene. In addition, seven new types of co-existed SNPs in the PGRN gene were found in nine patients. Unfortunately, SSCP failed because of the huge size of PCR products. Web-based splice sites predictors showed the novel deletion mutation (c.IVS8+23_+26delTGGG) might cause disturbances in the splicing of PGRN transcript, since it is located near one splice site. Protein function prediction for the functional effect in GRNs (3 isoforms) caused by the novel missense mutation (c.1767G>T, Leu589Phe; Leu434Phe and/or Leu409Phe) showed possibly damaging (0.878) or benign (0.176), probably damaging (0.998) or probably damaging (0.933), and probably damaging (0.958) or possibly damaging (0.536) results based on the structures of GRN1, GRN2 and GRN3, respectively. In silico models showed the novel missense mutation (c.1767G>T, Leu589Phe; Leu434Phe and/or Leu409Phe) was located in the random coil structure at the C-terminal of GRNs (3 isoforms). Since phenylalanine and leucine are nonpolar and hydrophobic animo acids, random coil structure at the C-ternimal of GRNs (3 isoforms) might be changed by this novel point mutation (c.1767G>T, Leu589Phe; Leu434Phe and/or Leu409Phe). This work provided new insight into study for FTD in Asia.
연관 검색어 추천
이 검색어로 많이 본 자료
활용도 높은 자료
