Title page
Acknowledgement
Contents
Abbreviations 11
I. Abstract 13
II. Introduction 15
III. Materials and Methods 19
III.1. Collection of human blood samples and genomic DNA preparation 19
III.2. Discrimination of whole-genome genotypes 19
III.3. Statistical analysis 20
IV. Results 22
IV.1. Three major genomic regions are associated with POF 22
IV.2. Association between polymorphisms in ACSL6 gene and POF 22
IV.3. Association between polymorphisms in BCKDHB gene and POF 30
IV.4. Association between polymorphisms in PTHB1 gene and POF 39
V. Discussion 48
V.1. POF-associated gene, ACSL6 48
V.2. POF-associated gene, BCKDHB 50
V.3. POF-associated gene, PTHB1 52
VI. References 55
Abstract 68
Table 1. HWE test for each SNPs in ACSL6 gene. 23
Table 2. Disease-association study for genotype distribution with 6 SNPs in ACSL6 gene in both groups. 25
Table 3. Haplotype block formed by pairwise LD test in ACSL6 gene. Gabriel's rule was used in this test. 28
Table 4. Disease-association study for haplotype model in ACSL6 gene. 29
Table 5. HWE test for each SNPs in BCKDHB gene. 33
Table 6. Disease-association study for genotype distribution with 10 SNPs in BCKDHB gene in both groups. 34
Table 7. Pair-wise LD analysis tested by Gabriel's fule in BCKDHB gene. 36
Table 8. Disease-association study for haplotype model in BCKDHB gene. 38
Table 9. HWE test for each SNPs in PTHB1 gene. 42
Table 10. Disease-association study for genotype distribution with 17 SNPs in PTHB1 gene in both groups. 43
Table 11. Pair-wise LD analysis tested by Gabriel's fule in PTHB1 gene. 45
Table 12. Disease-association study for haplotype model in PTHB1 gene. 46
Figure 1. The physical map of ACSL6 gene showing the total 6 SNPs examined in LD-based genome-wide association study and strong haplotype block formed by Gabriel’s rule. This gene is located at chromosome 5p31 and is transcribed into one of two transcription variants upon alternative splicing. This map was produced on the basis of the NM_015256 transcript at Entrez Gene (http://www.ncbi.nlm.nih.gov/entrez/), which is composed of 21 exons. The empty squares indicate the 5´- and... 27
Figure 2. The physical map with 27 SNPs in BCKDHB gene. This gene was transcribed to one of two transcript variants. This gene map was described on the NM_183050. Through the LD analysis, three haplotype blocks (HBs) were formed, among them, two HBs, HB2 and HB3 are in complete LD. 31
Figure 3. The physical map of PTHB1 gene showing the total 24 SNPs examined in this study. This gene is located at chromosome 7p14 and is transcribed into one of four transcription variants upon alternative splicing. This map was produced on the basis of the NM_198428 transcript at Entrez Gene... 40