The determination of ancestry is an important part of an individual's identification when creating a biological profile. This thesis scrutinizes postcranial variation using over 65 osteometric sorting measurements in an attempt to identify those measurements that display the most significant differences among Koreans, Africans, and Europeans. Data was collected from four American skeletal collections and one South Korean skeletal collection for a total sample population of 306 individuals: 24 of Korean ancestry, 66 of African ancestry, and 216 of European ancestry. In an effort to minimize the number of measurements needed for ancestral assessment, stepwise discriminant analysis was performed for measurements of each skeletal region and region combinations. Initial findings highly misclassified Africans, so the results of this study were separated into two parts: Koreans from Africans/Europeans and Africans from Europeans. A majority of the functions developed in the first part of the analysis resulted in cross-validated classifications of 80% and greater for Koreans and 77% or greater for Africans/Europeans with the highest classifying function for both ancestral groups being composed of upper limb measurements. Most of the discriminant functions from the second part of the analysis correctly differentiated Africans with 70% or greater accuracy and Europeans with 72% or greater accuracy with the highest classifying function for both groups consisting of pelvis, lower limb, and foot measurements. These functions indicate that ancestry can be determined successfully from postcranial elements; that certain skeletal regions are better indicators of ancestry than others; and that osteological remains do not need to be complete to develop an informative biological profile.

An analysis of mitochondrial DNA (mtDNA) restriction fragment length polymorphisms (RFLPs) was done with the primary goal of clarifying the relationship of the Indian population to world populations. Phylogenetically informative RFLP sites were amplified, restricted and scored for 187 Indian-descended individuals. This sample collectively represented a geographically wide distribution, the three main religions present in the subcontinent, and three main caste groups. Thirteen haplotypes were found in the Indian population, and when combined with world population data obtained from the literature, 41 different haplotypes were found. India was found to be significantly different from all world populations under study. In agreement with previously reported results, the Indian population was found to be more similar to European populations than south-east Asian populations, with all Indian populations sharing the European-associated haplotypes 14 and 15 at high frequencies. However, high frequencies of haplotype 30 implied similarity with the Evenk population of Siberia, suggesting a possible north-central Asian origin for the Dravidian and/or Indo-Aryan migration into India. Significant geographical differentiation within India was found, with north-western India having significantly higher frequencies of haplotypes 14 and 15 than Southern India, and lower frequencies of the Evenk-associated haplotype 30. The northwest was also significantly more diverse than other regions of India, most likely due to its location on the main routes of repeated migration into India. Significant differences between religious groups were found to have a geographical basis, while caste groups were undifferentiated from each other and the main religious groups. / Thesis / Master of Science (MS)

ABSTRACT There is substantial evidence to suggest that independent of conventional BP, LV mass (LVM) is higher in African-Americans than in European-Americans a difference that may translate into a higher prevalence of cardiovascular diseases. In the present thesis I assessed whether LVM is similarly elevated in groups of African descent living in Africa, and subsequently whether 24-hour, day or night BP or indices of arterial stiffness could explain the variability in LVM beyond conventional BP in this population group. As there is considerable controversy as to whether 24-hour BP measurements are better predictors of the regression of LVH than conventional BP and whether antihypertensive agents that target the renin-angiotensin system (RAS) regress LV hypertrophy (LVH) independent of BP in groups of African descent, in the present thesis I therefore also assessed these questions. In 141 healthy adult participants obtained from a random sample of nuclear families (n=399) of African ancestry living in Soweto, I determined that LVM adjusted for body surface area to the first power was an appropriate allometric signal to account for growth effects on LVM. The allometric signals established in other populations considerably over-adjusted for LVM in the group that I studied with marked negative relations noted. After adjusting for body surface area I noted upper thresholds of LVM index (LVMI) of 134 g/m2 for men and 112 g/m2 for women. As compared to thresholds described for other population samples these thresholds were noted to be modestly higher. In 187 women from randomly recruited nuclear families of African ancestry, after appropriate adjustments, conventional BP was as closely associated with LVMI as 24- hour BP, and daytime BP was as closely associated with LVMI as night-time BP in women. However, in 110 men from randomly recruited nuclear families of African ancestry, after appropriate adjustments, only night-time BP was associated with LVMI, an effect that was independent of conventional BP (r=0.21, p<0.05). Indices of nocturnal decreases in BP were not associated with LVMI in either gender group. Furthermore, in randomly recruited nuclear families of African ancestry, after appropriate adjustments, including systolic BP or pulse pressure, pulse wave velocity (an index of arterial stiffness assessed using applanation tonometry) was independently associated with LVMI in women (n=204, r=0.25, p<0.0005), but not in men (n=123, r=-0.07). In 173 hypertensive patients of African descent of whom 64 were previously untreated and 109 were previously treated, I assessed whether ambulatory BP is a better predictor of on-treatment decreases in LVMI over a 4 month treatment period. In the previously untreated patients, the regression in LVMI correlated to a similar degree (p<0.09) with decreases in conventional (r=0.34; p<0.005) and 24-hour (r=0.26; p<0.04) systolic BP. In this same study sample followed prospectively for 25 months, accounting for effects on ambulatory BP at each time point, the use of the angiotensin-converting enzyme inhibitor, enalapril, was not associated with LVMI, whereas, on-treatment conventional systolic BP (p=0.01) and night-time systolic BP (p=0.01) were associated with LVMI. In a further study conducted in 87 patients of African ancestry with hypertension and LVH, I showed that changes in systolic ambulatory BP (daytime, r=0.46, p=0.006) were predictive of changes in LVMI after 2 months of treatment with an angiotensin II receptor blocker (candesartan), ACE-I (ramipril) and the diuretic agent, hydrochlorothiazide. Moreover, in a final study I showed that in hypertensive patients of African ancestry, initiating therapy with the diuretic, indapamide SR and then adding the ACE-I, perindopril 4 mg (n=42), was equally as effective as amlodipine (calcium channel blocker) (n=44) therapy at reducing ambulatory BP and LVMI. Thus, in conclusion, groups of African descent living in Africa have only marginally higher thresholds for LVM than other population groups. Moreover, in this population group, nocturnal BP has a conventional BP-independent effect on LVMI in men, but not in women, whereas arterial stiffness has a conventional BP-independent effect on LVMI in women, but not in men. Further, in this population, reductions in LVM produced by antihypertensive therapy appear to be equally as closely related to conventional as ambulatory BP and in contrast to findings in groups of European ancestry, where RAS blockers produce unique benefits on LVM beyond conventional BP reductions, in groups of African ancestry in Africa, RAS blockers produce no BPindependent reductions in LVM. Moreover, in this population, decreases in LVM in patients with LVH produced by RAS blockers are related to ambulatory BP changes and despite the ineffectiveness of RAS blockers on BP when used as monotherapy in this population, RAS blockers together with diuretics are equally as effective in decreasing BP and LVM as compared to a class of antihypertensive agents with established efficacy (calcium channel blockers). Hence when compelling indications for RAS blockade exist, RAS blocker-diuretic combinations are effective therapy in patients of African descent living in Africa.

No description available.

Seven microsatellites, DYS 388, DYS 3891, DYS 389II, DYS 390, DYS 391, DYS 392 and DYS 393 and a biallelic locus DYS 271 were analyzed in the Indian population with the aim of understanding the relationships of the Indo-European and the Dravidian population of India with those of the European /Central Asian populations. The 116 Indian samples, used in the study, enjoy a wide geographical distribution and represents well the different religions and caste groups of India. Supporting previously published results, most variation is found between populations within continents than between continents. No significant differences were found between the different religious and caste groups of India with those of the World populations. All the alleles of the different markers are well represented in the different ethnic groups of India, and thus, does not support the popular belief that the highest diversity exists within the middle caste. Significant differences in the distribution of alleles are found in different regions of India especially between the North and the South. A phylogenetic relationship appears to exist between the Sindhis from South Pakistan with those of the South Indian population. This lends support to the belief that the present population from Sind might represent a remnant population of the original inhabitant of the region that was mainly pushed further to the Southern part of Subcontinent by later invasions. A phylogenetic relationship also exists between the Indian population and the Burushaski population from Northwest Pakistan and with the Kazakhs, Kirgiz and the Uighurs from Central Asia. This is in agreement with previously published results, and supports the occurrence of two main population movements from Central Asia into India at different time intervals that gave birth to the two main language families-the Dravidian and the Indo-European languages in India. / Thesis / Master of Science (MS)

BACKGROUND: The study of genetic variants alone is not enough to explain a complex disease like cancer. Alterations in DNA methylation patterns have been associated with different types of tumor. In order to detect markers of susceptibility for the development of cutaneous melanoma and breast cancer in the Uruguayan population, we integrated genetic and epigenetic information of patients and controls. METHODS: We performed two case-control studies that included 49 individuals with sporadic cutaneous melanoma and 73 unaffected controls, and 179 women with sporadic breast cancer and 209 women controls. We determined the level of global leukocyte DNA methylation using relative quantification of 5mdC by HPLC, and we compared methylation levels between cases and controls with nonparametric statistical tests. Since the Uruguayan population is admixed and both melanoma and breast cancer have very high incidences in Uruguay compared to other populations, we examined whether individual ancestry influences global leucocyte DNA methylation status. We carried out a correlation analysis between the percentage of African, European and Native American individual ancestries, determined using 59 ancestry informative markers, and global DNA methylation in all participants. RESULTS: We detected global DNA hypomethylation in leukocytes of melanoma and breast cancer patients compared with healthy controls (p < 0.001). Additionally, we found a negative correlation between African ancestry and global DNA methylation in cancer patients (p <0.005). CONCLUSIONS: These results support the potential use of global DNA methylation as a biomarker for cancer risk. In addition, our findings suggest that the ancestral genome structure generated by the admixture process influences DNA methylation patterns, and underscore the importance of considering genetic ancestry as a modifying factor in epigenetic association studies in admixed populations such as Latino ones.

IT2018

This analysis examined cranial epigenetic and morphological nonmetric traits in 756 subadults (fetal to <20 years), in European, African, and Asian samples. The goals of this research were to assess: the age and manner in which nonmetric traits develop and if variation between geographic groupings is present in subadults; the role of the adolescent growth spurt in trait expression; the feasibility of utilizing subadult crania in biological distance studies and ancestry assessment. A number of epigenetic and morphological traits show a primarily genetic versus developmental basis, suggested by the fact that there was no difference in trait frequencies between the fetal/0-3 and 15-20 year age categories. Eighty-five percent of epigenetic traits appear before 3 years; 54% were age stable by 3 years, and 75% were stable before age ten. Geographic cranial variation is present at an early age as demonstrated by the appearance of 58% of morphological traits before age 3, and 90% by age 10. Ten and a half percent of morphological traits are age stable before 3 years of age, 48% by age 10. Traits statistically significant between pre-pubertal and pubertal and/or pubertal and post pubertal individuals are hyperostotic, functional, and in some cases, sex dependent. Few epigenetic (1.3%) and morphological traits (7.9%) were found to be sex dependent, possibly because sexually dimorphism may not be fully expressed in individuals in the 15-20 year age category. Features that indicate ancestry develop before puberty, and do not require the onset of puberty and sexual dimorphism to be fully formed. Three-quarters of epigenetic traits were age stable and showed trait frequencies similar to adults before 10 years of age, suggesting subadults could be included in biodistance studies using these traits. Twenty-four morphological traits were statistically significant between geographic groups and show promise for future use in the forensic analysis of ancestry assessment in children.

This analysis examined cranial epigenetic and morphological nonmetric traits in 756 subadults (fetal to <20 years), in European, African, and Asian samples. The goals of this research were to assess: the age and manner in which nonmetric traits develop and if variation between geographic groupings is present in subadults; the role of the adolescent growth spurt in trait expression; the feasibility of utilizing subadult crania in biological distance studies and ancestry assessment. A number of epigenetic and morphological traits show a primarily genetic versus developmental basis, suggested by the fact that there was no difference in trait frequencies between the fetal/0-3 and 15-20 year age categories. Eighty-five percent of epigenetic traits appear before 3 years; 54% were age stable by 3 years, and 75% were stable before age ten. Geographic cranial variation is present at an early age as demonstrated by the appearance of 58% of morphological traits before age 3, and 90% by age 10. Ten and a half percent of morphological traits are age stable before 3 years of age, 48% by age 10. Traits statistically significant between pre-pubertal and pubertal and/or pubertal and post pubertal individuals are hyperostotic, functional, and in some cases, sex dependent. Few epigenetic (1.3%) and morphological traits (7.9%) were found to be sex dependent, possibly because sexually dimorphism may not be fully expressed in individuals in the 15-20 year age category. Features that indicate ancestry develop before puberty, and do not require the onset of puberty and sexual dimorphism to be fully formed. Three-quarters of epigenetic traits were age stable and showed trait frequencies similar to adults before 10 years of age, suggesting subadults could be included in biodistance studies using these traits. Twenty-four morphological traits were statistically significant between geographic groups and show promise for future use in the forensic analysis of ancestry assessment in children.

The natural history of scar maturation in humans has been described by Bond et al. (2008b) in a male European Continental Ancestry Group (ECAG). It is important that the natural history of scar maturation in humans is established for all skin types. This study therefore aims to describe clinically and histologically the maturation of scars in male volunteers from the African Continental Ancestry Group (ACAG).This study was performed as a single centre, methodology trial. Three incisions and a punch biopsy were carried out on each arm. Monthly assessments of the resultant scars included: investigator scar assessments; scar photography; VAS scoring by an Independent External Scar Assessment Panel; and objective measures of colour and scar mechanics. At various time points scars were excised for histology. Sixty male subjects of African Continental Ancestry between the ages of 18-56 years were recruited to take part in the study. The clinical appearance of a scar in the ACAG improves with time. Scar colour mismatch decreases and the mechanical properties of scars improve with time. Scar width increased over the 12 months. With the exception of scar contour and scar redness, a steady state was not achieved. Volunteer skin type was shown to influence the resulting scar appearance and not age. The histology of scar maturation in the ACAG over 12 months was described and scars classified into three groups each displaying a different rate of longitudinal progression of scar maturation. The process of collagen maturation is still ongoing at month 12; many scars demonstrated a prolonged high turnover state of collagen synthesis and degradation, rete ridge restoration and angiogenesis were still ongoing with persistent inflammation identified in scars up to Month 12. There is a strong correlation shown between the Clinical VAS scores and the Histology VAS scores for the papillary dermis which is of better quality than the reticular dermis. There is some evidence that young people (ACAG) and volunteers with darker skin have poorer scar histology. The spectrophotometry data indicated that the Fitzpatrick Skin Type Classification is a useful method of classifying the varying skin colours of this group of volunteers. In conclusion, scar maturation in the ACAG occurs as a series of defined macroscopic and microscopic stages over the course of 1 year. The process of scar maturation is not complete at 12 months. All scars showed evidence of improvement over the course of the study influenced in part by volunteer skin type and age. Results suggest that scar maturation in this study group occurs at a different rate and is of a different quality, compared to current knowledge of scar maturation in the ECAG.