Northern Sweden shows a unique population structure with remarkable geographical variations in the distribution of genetic disorders as well as genetic markers like blood groups, serum groups and red cell enzyme types. The present-day population of northern Sweden is a mixture of people of Finnish, Saamish (Lappish) and Central-Swedish origin. In this thesis the ethnic heterogeneity of the North-Swedish population (counties of Västerbotten and Norrbotten) was studied using genetic blood markers, and the epidemiological impact of the ethnic heterogeneity was exemplified by studying the geographical correlation between Finnish admixture and risk factors for cardiovascular diseases. The following results were found: 1 Two new ethnic marker genes were discovered: the GC*1F allele (GC serum groups) for Saamish influence and the TF*C3 allele (transferrin serum groups) for Finnish influence. 2 Regional gene frequency variations in the A1A2B0 blood groups, 6-phosphogluconate dehydrogenase (6-PGD) types and transferrin and GC serum groups were studied in a sample of 4100-5600 individuals from northern Sweden distributed according to birth place into 23 subpopulations. A significant regional heterogeneity was found in all systems. The ethnic marker genes (AB0*A2, GC*1F, TF*C3, PGD*C) showed clineal variations consistent with the expected patterns of Finnish and Saamish admixture. 3 Finnish and Saamish admixture was estimated in the 23 subpopulations using AB0*A2, GC*1F and PGD*C as Saamish markers and TF*C3, TF*DCHI, TF*B0-1 and SODI*2 as Finnish markers. The Saamish admixture varied between 0 and 34% and was strongest in the northern and northwestern parts of northern Sweden. The Finnish influence varied between 0 and 84% and was strongest in the northern and northeastern parts of the area. The ethnic marker genes showed significant geographical intercorrelations. 4 Hypercholesterolemia showed a significant heterogeneity between the 23 subpopulations, and there was a significant geographical covariation with the degree of Finnish admixture. These results are consistent with the hypothesis that Finnish genetic influence may contribute to the development of hypercholesterolemia and thereby to the increased rate of cardiovascular diseases found in northern Sweden. The results of this study suggest that in addition to the founder effect ethnic heterogeneity is an important determinant of the structure of the North-Swedish population. / <p>Diss. (sammanfattning) Umeå : Umeå universitet, 1992, härtill 7 uppsatser.</p> / digitalisering@umu.se

The occurrence of clinically diagnosed and/or ruptured abdominal aortic aneurysms (AAAs) in the families of 220 patients with AAAs, treated at the Surgical Clinic, University Hospital of Umeå in the northern part of Sweden during the years 1965-82, was studied. A questionnaire concerning the blood relatives was answered by 87/89 patients. 16/87 patients (18%) had blood relatives with AAAs. In 14 families one blood relative was affected, and in 2 families two blood relatives were affected. First degree relatives were affected in 9/87 cases (10%), and second degree relatives in 7/87 cases (8%). 9/468 (1.9%) of the patients' brothers and sisters but only five of all their cousins had AAAs, and 7/204 (3.4%) of the dead brothers and sisters had died of ruptured AAAs. Concerning the patients who were not included in the letter survey at least 14/133had blood relatives with AAAs. However, the great majority of these patients were dead when the study was performed and could not be asked aboutthe occurrence of AAAs in their families. The patients with AAAs had significantly higher serum concentrations of triglyceride and (YLDL + LDL)-cholesterol and a significantly lower serum concentration of HDL-cholesterol than randomly selected healthy controls of the same sex and age as the patients. We also compared the distributions of genetic markers (HLA antigens, the blood group systems ABO, Rh, MNSs, P, Kell, Lewis and Duffy and the serum protein group systems haptoglobin, transferrin, group-specific component, complement C3, properdin factor and alpha-1-antitrypsin) in patients with AAAs with the distributions in controls and in some cases with the expected distributions according to the Hardy-Weinberg law. A significantly decreased frequency of Rh-negative individuals, and significantly increased frequencies of Kell-positi ve individuals, of MN heterozygotes and of heterozygotes concerning haptoglobin type was found. Furthermore, the aneurysm walls of patients with and without AAAs in the family were compared concerning the morphology, but no differences were found. We also studied the occurrence of collagen types I and III in the aneurysm walls, and the occurrence of vimentin and desmin in the smooth muscle cells of the aneurysm walls, but all these components were present in the aneurysm walls of both the patients with and those without AAAs in the family. To summarize the results, there seems to be an increased frequency of AAAs, and especially of ruptured AAAs, among the brothers and sisters of patients with AAAs. Elevated serum concentrations of triglyceride and (VLDL + LDL)- cholesterol and a lowered serum concentration of HDL-cholesterol seems to be common in patients with AAAs. There seems to be a hereditary predisposition to the development of AAAs, because we found associations with four different genetic markers (Rh, MN, Kell, haptoglobin group). However, there is probably no specific "familial" type of AAAs, because we found no differences between the patients with and those without AAAs in the family.Key words: / <p>S. 1-42: sammanfattning, s. 43-103: 5 uppsatser</p> / digitalisering@umu

The aim of this thesis was to investigate the possibility of using buccal cells derived from a multi layered epithelial tissue from the oral mucosa as a model to identify potential biomarkers of genomic instability in relation to normal ageing and premature ageing syndromes such as AD and DS. A buccal micronucleus cytome assay was developed and used to investigate biomarkers for DNA damage, cell proliferation and cell death in healthy young, healthy old and young Down’s syndrome cohorts. Cells with micronuclei, karyorrhectic cells, condensed chromatin cells and basal cells increased significantly with normal ageing (P<0.0001). Cells with micronuclei and binucleated cells increased (P<0.0001) and condensed chromatin, karyorrhectic, karyolytic and pyknotic cells decreased (P<0.002) significantly in Down’s syndrome relative to young controls. The buccal micronucleus cytome assay was used to measure ratios of buccal cell populations and micronuclei in clinically diagnosed Alzheimer’s patients compared to age and gender matched controls. Frequencies of basal cells (P<0.0001), condensed chromatin cells (P<0.0001) and karyorrhectic cells (P<0.0001) were found to be significantly lower in Alzheimer’s patients, possibly reflecting changes in the cellular kinetics or structural profile of the buccal mucosa. Changes in telomere length were investigated using a quantitative RTm-PCR method to measure absolute telomere length (in Kb per diploid genome) and show agerelated changes in white blood cells and buccal cell telomere length (in kb per diploid genome) in normal healthy individuals and Alzheimer’s patients. We observed a significantly lower telomere length in white blood cells (P<0.0001) and buccal cells (P<0.01) in Alzheimer’s patients relative to healthy age-matched controls (31.4% and 32.3% respectively). However, there was a significantly greater telomere length in hippocampus cells of Alzheimer’s brains (P=0.01) compared to control samples (49.0). Buccal cells were also used to investigate chromosome 17 and 21 aneuploidy. A 1.5 fold increase in trisomy 21 (P<0.001) and a 1.2 fold increase in trisomy 17 (P<0.001) was observed in buccal cells of Alzheimer’s patients compared to age and gender matched controls. Chromosome 17 and chromosome 21 monosomy and trisomy increase significantly with age (P<0.001). Down’s syndrome, which exhibits similar neuropathological features to those observed in Alzheimer’s disease also showed a strong increase in chromosome 17 monosomy and trisomy compared to matched controls (P<0.001). However, aneuploidy rate for chromosome 17 and 21 in the nuclei of hippocampus cells of brains from Alzheimer’s patients and controls were not significantly different. Observations that AD individuals have altered plasma folate, B12 and Hcy levels compared to age-matched controls who have not been clinically diagnosed with AD were investigated. Genotyping studies were undertaken to determine whether polymorphisms within particular genes of the folate methionine pathway contributed to AD pathogenesis. Correlations between folate, B12 and Hcy status with previously determined buccal micronucleus assay cytome biomarkers for DNA damage, cell proliferation and cell death markers was investigated. Lastly, the potential protective effects of phytonutrient polyphenols on genomic instability events in a transgenic mouse model for AD were investigated. We determined the effects of curcumin and GSE polyphenols on DNA damage by testing the mice over a 9 month period utilizing a buccal micronucleus cytome assay, an erythrocyte micronucleus assay and measuring telomere length in both buccal cells and olfactory lobe brain tissue. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1313395 / Thesis (Ph.D.) -- The University of Adelaide, School of Molecular and Biomedical Science, 2008

Errata slip inserted. / Bibliogaphy: leaves [93-109]. / x, 92, [17] leaves, [20] leaves of plates : ill. ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Identifes and maps markers associated with the quality traits of grain protein content, milling yield and flour colour, and with genes resistant to stem- and leaf-rust diseases in wheat. / Thesis (Ph.D.)--University of Adelaide, Dept. of Plant Science, Waite Agricultural Research Institute, 1998

The aim of this thesis was to investigate the possibility of using buccal cells derived from a multi layered epithelial tissue from the oral mucosa as a model to identify potential biomarkers of genomic instability in relation to normal ageing and premature ageing syndromes such as AD and DS. A buccal micronucleus cytome assay was developed and used to investigate biomarkers for DNA damage, cell proliferation and cell death in healthy young, healthy old and young Down’s syndrome cohorts. Cells with micronuclei, karyorrhectic cells, condensed chromatin cells and basal cells increased significantly with normal ageing (P<0.0001). Cells with micronuclei and binucleated cells increased (P<0.0001) and condensed chromatin, karyorrhectic, karyolytic and pyknotic cells decreased (P<0.002) significantly in Down’s syndrome relative to young controls. The buccal micronucleus cytome assay was used to measure ratios of buccal cell populations and micronuclei in clinically diagnosed Alzheimer’s patients compared to age and gender matched controls. Frequencies of basal cells (P<0.0001), condensed chromatin cells (P<0.0001) and karyorrhectic cells (P<0.0001) were found to be significantly lower in Alzheimer’s patients, possibly reflecting changes in the cellular kinetics or structural profile of the buccal mucosa. Changes in telomere length were investigated using a quantitative RTm-PCR method to measure absolute telomere length (in Kb per diploid genome) and show agerelated changes in white blood cells and buccal cell telomere length (in kb per diploid genome) in normal healthy individuals and Alzheimer’s patients. We observed a significantly lower telomere length in white blood cells (P<0.0001) and buccal cells (P<0.01) in Alzheimer’s patients relative to healthy age-matched controls (31.4% and 32.3% respectively). However, there was a significantly greater telomere length in hippocampus cells of Alzheimer’s brains (P=0.01) compared to control samples (49.0). Buccal cells were also used to investigate chromosome 17 and 21 aneuploidy. A 1.5 fold increase in trisomy 21 (P<0.001) and a 1.2 fold increase in trisomy 17 (P<0.001) was observed in buccal cells of Alzheimer’s patients compared to age and gender matched controls. Chromosome 17 and chromosome 21 monosomy and trisomy increase significantly with age (P<0.001). Down’s syndrome, which exhibits similar neuropathological features to those observed in Alzheimer’s disease also showed a strong increase in chromosome 17 monosomy and trisomy compared to matched controls (P<0.001). However, aneuploidy rate for chromosome 17 and 21 in the nuclei of hippocampus cells of brains from Alzheimer’s patients and controls were not significantly different. Observations that AD individuals have altered plasma folate, B12 and Hcy levels compared to age-matched controls who have not been clinically diagnosed with AD were investigated. Genotyping studies were undertaken to determine whether polymorphisms within particular genes of the folate methionine pathway contributed to AD pathogenesis. Correlations between folate, B12 and Hcy status with previously determined buccal micronucleus assay cytome biomarkers for DNA damage, cell proliferation and cell death markers was investigated. Lastly, the potential protective effects of phytonutrient polyphenols on genomic instability events in a transgenic mouse model for AD were investigated. We determined the effects of curcumin and GSE polyphenols on DNA damage by testing the mice over a 9 month period utilizing a buccal micronucleus cytome assay, an erythrocyte micronucleus assay and measuring telomere length in both buccal cells and olfactory lobe brain tissue. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1313395 / Thesis (Ph.D.) -- The University of Adelaide, School of Molecular and Biomedical Science, 2008

Diss. (sammanfattning). Alnarp : Sveriges lantbruksuniversitet, 2005. / Härtill 4 uppsatser.

Diss. (sammanfattning) Skara : Sveriges lantbruksuniv., 2002. / Härtill 4 uppsatser.

Licentiatavhandling (sammanfattning) Stockholm : Karol. inst., 2003. / Härtill 3 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2002. / Härtill 7 uppsatser.

Diss. (sammanfattning) Uppsala : Sveriges lantbruksuniv., 2003. / Härtill 4 uppsatser.