عنوان

Genetic variation of the human mitochondrial DNA in natural and disease states

شماره

TLpq304062442

زبان متن نوشتاري يا گفتاري و مانند آن

انگلیسی

عنوان اصلي

Genetic variation of the human mitochondrial DNA in natural and disease states

نام عام مواد

[Thesis]

نام نخستين پديدآور

S. W. Ballinger

نام ساير پديدآوران

D. C. Wallace

نام ناشر، پخش کننده و غيره

Emory University

تاریخ نشرو بخش و غیره

1993

نام خاص و کميت اثر

197

جزئيات پايان نامه و نوع درجه آن

Ph.D.

کسي که مدرک را اعطا کرده

Emory University

امتياز متن

1993

متن يادداشت

A prediction of the mitochondrial genetic paradigm is that some forms of chronic degenerative disease will be due to mitochondrial DNA (mtDNA) mutations (Wallace, 1992a). To investigate this possibility, my research had two related goals. The first was to characterize the natural genetic variation of the human mtDNA. These data would be essential to the second goal, which was to identify mtDNA mutations associated with disease. Investigation of natural mtDNA genetic variation also helped define the origins of both Asians and Amerindians. The majority of the mtDNA genetic variation in Asian populations is shared, indicating that they share a common ancestry (Ballinger et al., 1992a). Additionally, genetic remnants of the Papua New Guinea founders were observed in Malaysia, and a frequency cline for the COII/tRNALys intergenic deletion was observed along coastal Asia (Ballinger et al., 1992a). Comparison of Asian and Native American mtDNA haplotype data revealed that all Amerindians can be traced back to four Asian mtDNA lineages (Schurr et al., 1990; Torroni et al., 1992). Genetic analyses showed that several mtDNA mutations could be responsible for chronic degenerative disease. First, mtDNA point mutations were found to be responsible for both Myoclonic Epilepsy and Ragged Red Fiber disease (MERRF) and Leigh's disease. MERRF is a chronic neurodegenerative disease caused by a heteroplasmic A to G transition at np 8344 in tRNALys (Shoffner et al., 1990). Leigh's disease is an early onset neurodegenerative disorder caused by a heteroplasmic T to G transversion mutation at np 8993 in the ATPase 6 subunit of the mtDNA (Shoffner et al., 1992). The severity of both diseases correlated with the percent heteroplasmic mutant and age. Second, major mtDNA length mutations were found to cause both Pearson's syndrome (Rotig et al., 1988, 1990; Ballinger et al., 1993) and Diabetes mellitus (Ballinger et al., 1992b). MtDNA deletions were associated with Pearson's syndrome, a disease characterized by pancytopenia. Diabetes mellitus was found to be associated with major mtDNA length mutations in a family with adult onset diabetes. Consequently, these data show that mtDNA mutations can be responsible for at least four different types of chronic degenerative disease, supporting the hypothesis predicted by the mitochondrial genetic paradigm.

موضوع مستند نشده

Asian ancestry

موضوع مستند نشده

Biological sciences

موضوع مستند نشده

diabetes mellitus

موضوع مستند نشده

Leigh's disease

موضوع مستند نشده

Native American

موضوع مستند نشده

Pure sciences

مستند نام اشخاص تاييد نشده

D. C. Wallace

مستند نام اشخاص تاييد نشده

S. W. Ballinger

نام الکترونيکي

فرمت انتشار

p

نوع ماده

[Thesis]

کد کاربرگه

276903

سطح دسترسي

a

تكميل شده

Y