Most of the common human diseases, including tumor, cardiovascular and cerebrovascular disease, metabolic disease, nervous disease and respiratory disease, are complex diseases. They are not caused by one gene or one factor but polygenes and multiple factors which is different form single-gene disorders. Complex diseases do not obey the standard Mendelian patterns of inheritance, and are a results of combination of genetic, environmental, and lifestyle factors, most of which have not yet been identified. So it is very difficult to study them. In this thesis, we focus on the genetic mechanism of mitochondrial disorder and tumor, to further elucidate the pathogenesis of these complex diseases. In the first part of this thesis, we studied the relationship between mitochondrial DNA (mtDNA) and Leigh syndrome (LS). First, we summarized the mitochondrial diseases in Chapter 1.Then we studied the molecular genetic mechanisms of LS (Chapter 2). LS is a typical mitochondrial disorder and closely related with mtDNA. We scanned the reported 17 mtDNA mutations involved in LS in our 198 Chinese LS patients. There are 8 patients having mtDNA mutations, including 2 patients with A3243G, 3 patients with T10109C, 2 patients with G13513A and 1 patient with G14459A. We did not detect these four mutations in all of the controls, which confirms that these mutations are involved with LS in deed in our patients. The frequency of mtDNA mutations is 4% in our LS patients, which is less than other reports. This difference may be caused by the different genetic background of study populations. There may be novel mtDNA mutations in our patients. In conclusion, the mtDNA mutations have a special spectrum in Chinese LS patients. Although Leigh syndrome is a typical mitochondrial disorder, it is not clear whether matrilineal background has contributed to this disease. To address this issue, we extensively studied and compared the haplogroup composition of a sample of 171 Chinese LS patients with that of 1597 controls. Our results show that haplogroups Y and B5 may increase the risk of LS in Chinese. Both haplogroups belong to macro-haplogroup N and share a common reverse mutation on nucleotide position 10398. Their common ground, A10398G combined haplogroup N may be the root of effect and conferred a higher risk for LS. The second part of the thesis focused on the molecular genetic study of esophageal cancer and breast tumor, to further elucidate the mechanism of tumorigenesis.
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