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한국 여아를 대상으로 한 전장유전체분석을 통한 새로운 성조숙증 연관 유전변이의 동정
- Alternative Title
- Gijeong Kim
- Author(s)
- 김기정
- Alternative Author(s)
- Gijeong Kim
- Advisor
- 정선용
- Department
- 일반대학원 의생명과학과
- Publisher
- The Graduate School, Ajou University
- Publication Year
- 2019--2
- Language
- eng
- Alternative Abstract
- Precocious puberty results from the activation of the hypothalamus-pituitary-gonadal axis at an early stage, which lead to the secretion of gonadotrophin-releasing hormone (GnRH) and can lead to physical and psychological problems such as loss of adult height, breast cancer, type 2 diabetes, and depression. Precocious puberty is caused by both genetic and environmental factors. Early diagnosis is very important for the effective treatment of the disease, because highly effective drugs are available for its treatment. The use of genetic biomarkers of precocious puberty might be a good solution could enable its early diagnosis. Although several genes, such as KISS1, KISS1R, and MKRN3 are known to be involved in precocious puberty, no genetic variants associated with precocious puberty have been identified yet using a genome-wide association study (GWAS). To identify genetic biomarker(s) for the early diagnosis of precocious puberty, I analyzed the genotype and clinical data of 696 Korean girls with precocious puberty and 300 Korean age-matched normal controls. After performing a case-control GWAS, I found eight genetic variants that are significantly associated with precocious puberty (p < 1.0 × 10-5), viz., rs10900855 (OR = 2.21 and p = 1.10 × 10-8), rs13187637 (OR = 2.006 and p = 7.07 × 10-7), rs373629 (OR = 0.5839 and p = 1.94 × 10-6), rs3849046 (OR = 1.959 and p = 2.24 × 10-6), rs56252016 (OR = 0.1212 and p = 3.48 × 10-6), rs62579679 (OR = 2.493 and p = 3.66 × 10-6), rs4680885 (OR = 0.4638 and p = 6.41 × 10-6), and rs4891764 (OR = 0.5933 and p = 8.66 × 10-6). The most significant SNP, rs10900855, exhibited a p- value at the GWAS-level of significance (p ≤ 5.0 × 10-8) and an extremely high OR value. By annotating and performing a signal plot analysis of the identified SNPs, I found that the SNPs were closely located to six genes: EGR1, HSPA9, ETF1, MAGI2, MPPED2, and DOK6. The gene expression patterns of the six genes in the hypothalamus tissue of female mice indicated a significant increase (EGR1) or a significant decrease (HSPA9, ETF1, MAGI2, MPPED2, and DOK6) in levels during the puberty period. In silico pathway analysis revealed that all six genes are closely associated with precocious puberty via two (EGR1) or three nodes (HSPA9, ETF1, MAGI2, MPPED2, and DOK6). These results indicate that the SNPs identified in these six genes were also closely associated with precocious puberty in girls.
- Fulltext
- Appears in Collections:
- Graduate School of Ajou University > Department of Biomedical Sciences > 3. Theses(Master)
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