Thèse d'exercice : Médecine. Médecine générale : Paris 12 : 2007. / Titre provenant de l'écran-titre. 67 f. ill. Bibliogr. f. 57-66.

Thèse de doctorat : Epidémiologie et santé publique : Nancy 1 : 2005. / Titre provenant de l'écran-titre.

published_or_final_version / Medicine / Master / Master of Research in Medicine

Genome-wide association studies (GWAS) have greatly improved our understanding of the genetic basis of complex traits. However, there are two major limitations with GWAS. First, most common variants identified by GWAS individually or in combination explain only a small proportion of heritability. This raises the possibility that additional forms of genetic variation, such as rare variants, could contribute to the missing heritability. The second limitation is that GWAS typically cannot identify which genes are being affected by the associated variants. Examination of rare variants, especially those in coding regions of the genome, can help address these issues. Moreover, several studies have recently identified low-frequency variants at both known and novel loci associated with complex traits, suggesting that functionally significant rare variants exist in the human population.

Studies in the United States suggest that girls are developing secondary sexual characteristics at earlier ages than in previous years, with non-Hispanic black girls in the United States experiencing menarche at an earlier age when compared to their peers. Early puberty and menarche may have multiple detrimental effects, including reduced adult height, increased risk of breast cancer, obesity, and endometrial cancer. In this thesis, data from published sources of height and skeletal information on non-Hispanic blacks dating from 1763 to 1861 in the United States are compared with modern population data from 1988 to 1994. The expected result is that the modern population should be taller than the historic population. This held true for males, but not for females. The sexes differed from each other in each population group. This could suggest that female maturation is under greater genetic control than male, compensating for harsh living conditions. / Department of Anthropology

Thesis (M.A.)--Southwest Texas State University, 1940. / Includes bibliographical references (leaves 65-67).

Thesis (M.A.)--Southwest Texas State University, 1940. / Includes bibliographical references (leaves 65-67).

Submitted by YURI TANI UTSUNOMIYA null (yuri.tani@yahoo.com.br) on 2018-01-08T12:45:05Z No. of bitstreams: 1 UTSUNOMIYA.pdf: 11784469 bytes, checksum: 9fc7d258b6e5e683b47b78ad25853acc (MD5) / Approved for entry into archive by Alexandra Maria Donadon Lusser Segali null (alexmar@fcav.unesp.br) on 2018-01-09T09:34:15Z (GMT) No. of bitstreams: 1 utsunomiya_yt_dr_jabo.pdf: 11784469 bytes, checksum: 9fc7d258b6e5e683b47b78ad25853acc (MD5) / Made available in DSpace on 2018-01-09T09:34:15Z (GMT). No. of bitstreams: 1 utsunomiya_yt_dr_jabo.pdf: 11784469 bytes, checksum: 9fc7d258b6e5e683b47b78ad25853acc (MD5) Previous issue date: 2017-12-06 / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / O gene 1 do adenoma pleomórfico (PLAG1) apresenta evidência de seleção positiva recente e associação com tamanho corporal e fertilidade em um grande número de raças bovinas ao redor do mundo. Tendo em vista sua recentemente descoberta função como fator de transcrição para o gene do fator de crescimento semelhante à insulina 2 (IGF2), o PLAG1 possui papel emergente como um dos principais reguladores do crescimento e da reprodução em bovinos. Apesar de sua importância, a variante de sequência de DNA responsável pelos efeitos pleiotrópicos atribuídos ao PLAG1 em bovinos permanece desconhecida. Também não está claro se a mesma mutação explica as associações fenótipo-genótipo encontradas em diferentes populações bovinas. Além disso, ainda é incerto onde e quando ocorreu a pressão de seleção responsável pelo aumento da frequência da mutação do PLAG1. No presente trabalho, reportamos o desenvolvimento de um pacote para o software estatístico R, o qual é direcionado à análise de haplótipos como preditores para variantes genéticas não observadas. Através da aplicação desta ferramenta a dados genômicos de bovinos oriundos de diversas regiões do mundo, encontramos evidência indicando que um único alelo derivado do PLAG1 aumentou em frequência rapidamente em bovinos Bos taurus do noroeste europeu entre os séculos XVI e XVIII. Este período é reconhecido como a última onda de aumento de estatura em bovinos por meio de registros arqueológicos. Os dados também sugerem que o alelo foi introgredido em B. taurus não europeu e raças Bos indicus entre os séculos XIX e XX, adquirindo uma distribuição quase global no último século. Análises de DNA antigo revelaram que esta mutação segrega em gado do noroeste europeu há pelo menos 1.000 anos. Em conjunto, estes resultados implicam um papel central da mutação do PLAG1 em recentes mudanças de tamanho corporal em bovinos. / The pleomorphic adenoma gene 1 (PLAG1) presents both evidence of recent positive selection and association with body size and fertility in a wide range of worldwide cattle breeds. Considering its recently uncovered function as a transcription factor for the insulin-like growth factor 2 gene (IGF2), PLAG1 is emerging as a major regulator of bovine growth and reproduction. In spite of its importance, the causal DNA sequence variant underlying the pleiotropic effects of PLAG1 in cattle remains unknown. It is also unclear whether the same mutation accounts for the phenotype-genotype associations detected across different cattle populations. Furthermore, when and where the selective pressure responsible for increasing the frequency of the PLAG1 mutation occurred is still uncertain. Here, we report the development of a package for the R statistical software to analyze haplotypes as surrogates for unobserved genetic variants. By applying this tool to genomic data of worldwide cattle breeds, we found evidence that a single bovine PLAG1 derived allele increased rapidly in frequency in Northwestern European Bos taurus populations between the 16th and 18th centuries. This period is recognized as the last wave of increase in bovine stature from archaeological data. The data also suggested that the allele was introgressed into non-European B. taurus and Bos indicus breeds towards the 19th and 20th centuries, achieving an almost global distribution in the last century. Ancient DNA analyses further revealed that this mutation has been segregating in Northwestern European cattle for at least 1,000 years. Altogether, these results implicate a major role of the PLAG1 mutation in recent changes in body size in cattle. / 2014/01095-8 / 2016/07531-0

Estimation of the biological profile from as many skeletal elements as possible is a necessity in both forensic and bioarchaeological contexts; this includes non-standard aspects of the biological profile, such as body mass index (BMI). BMI is a measure that allows for understanding of the composition of an individual and is traditionally divided into four groups: underweight, normal weight, overweight, and obese. BMI estimation incorporates both estimation of stature and body mass. The estimation of stature from skeletal elements is commonly included into the standard biological profile but the estimation of body mass needs to be further statistically validated to be consistently included. The bones of the foot, specifically the first metatarsal, may have the ability to estimate BMI given an allometric relationship to stature and the mechanical relationship to body mass. There are two commonly used methods for stature estimation, the anatomical method and the regression method. The anatomical method takes into account all of the skeletal elements that contribute to stature while the regression method relies on the allometric relationship between a skeletal element and living stature. A correlation between the metrics of the first metatarsal and living stature has been observed, and proposed as a method for valid stature estimation from the boney foot (Byers et al., 1989). Body mass estimation from skeletal elements relies on two theoretical frameworks: the morphometric and the mechanical approaches. The morphometric approach relies on the size relationship of the individual to body mass; the basic relationship between volume, density, and weight allows for body mass estimation. The body is thought of as a cylinder, and in order to understand the volume of this cylinder the diameter is needed. A commonly used proxy for this in the human body is skeletal bi-iliac breadth from rearticulated pelvic girdle. The mechanical method of body mass estimation relies on the ideas of biomechanical bone remodeling; the elements of the skeleton that are under higher forces, including weight, will remodel to minimize stress. A commonly used metric for the mechanical method of body mass estimation is the diameter of the head of the femur. The foot experiences nearly the entire weight force of the individual at any point in the gait cycle and is subject to the biomechanical remodeling that this force would induce. Therefore, the application of the mechanical framework for body mass estimation could stand true for the elements of the foot. The morphometric and mechanical approaches have been validated against one another on a large, geographically disparate population (Auerbach and Ruff, 2004), but have yet to be validated on a sample of known body mass. DeGroote and Humphrey (2011) test the ability of the first metatarsal to estimate femoral head diameter, body mass, and femoral length. The estimated femoral head diameter from the first metatarsal is used to estimate body mass via the morphometric approach and the femoral length is used to estimate living stature. The authors find that body mass and stature estimation methods from more commonly used skeletal elements compared well with the methods developed from the first metatarsal. This study examines 388 `White' individuals from the William M. Bass donated skeletal collection to test the reliability of the body mass estimates from femoral head diameter and bi-iliac breadth, stature from maximum femoral length, and body mass and stature from the metrics of the first metatarsal. This sample included individuals from all four of the BMI classes. This study finds that all of the skeletal indicators compare well with one another; there is no statistical difference in the stature estimates from the first metatarsal and the maximum length of the femur, and there is no statistical between all three of the body mass estimation methods. When compared to the forensic estimates of stature neither of the tested methods had statistical difference. Conversely, when the body mass estimates are compared to forensic body mass there was a statistical difference and when further investigated the most difference in the body mass estimates was in the extremes of body mass (the underweight and obese categories). These findings indicate that the estimation of stature from both the maximum femoral length and the metrics of the metatarsal are accurate methods. Furthermore, the estimation of body mass is accurate when the individual is in the middle range of the BMI spectrum while these methods for outlying individuals are inaccurate. These findings have implications for the application of stature and body mass estimation in the fields of bioarchaeology, forensic anthropology, and paleoanthropology.

Orientadora: Profª. Drª. Maria Elizete Kunkel / Dissertação (mestrado) - Universidade Federal do ABC. Programa de Pós-Graduação em Engenharia Biomédica, 2016. / O Brasil não possui uma base nacional de dados antropométricos de mãos. Este tipo de dados é fundamental para estudos de forense, biomecânica e ergonomia. A estatura, assim como sexo, idade e etnia é um dado fundamental na identificação humana. Equações de regressão podem ser usadas para a estimativa da estatura de uma pessoa a partir de medidas de parâmetros antropométricos da mão. Nesta pesquisa foi criada uma base de dados de medidas antropométricas das mãos e estaturas. Equações de regressão linear foram geradas para estimativa de estatura de uma pessoa a partir de uma medida da sua mão. A amostra totalizou 427 voluntários do estado de São Paulo (56,4% mulheres e 43,6% homens) com idade entre 18 e 60 anos. As medidas de comprimento e largura das mãos e comprimento dos dedos de 854 mãos foram obtidas de modo direto, com um paquímetro digital, e de modo indireto e semiautomático, com um software a partir das imagens das mãos digitalizadas. Tanto os valores numéricos quando as fotos da base de dados, MaoBD, serão disponibilizados em http://goo.gl/95s5Bz. A avaliação comparativa entre os métodos verificou pequenas discordâncias entre eles, porém o método indireto resultou em uma forma mais rápida e de baixo custo para a coleta dos dados podendo ser usado para ampliar a base de dados para representar a população brasileira. O comprimento da palma da mão foi o melhor parâmetro para estimativa de estatura. / Brazil does not have a national base of anthropometric data from hands. This type of data is critical to forensic biomechanics and ergonomics studies. Stature, as well as gender, age and ethnicity, are important data in human identification. Regression equations can be used to estimate the stature of a person from anthropometric measurements of the hand. In this research, an anthropometric database of the hands and statures was created. Linear regression equations were generated to mestimate the stature of a person from a measure of their hand. The sample has 427 volunteers of São Paulo (56.4% women and 43.6% men) aged between 18 and 60 years. Length and width of the hands and finger length of 854 hands were obtained in a direct method, with a digital caliper, and with an indirect and semi-automatic method by using a software to analyse digitalized images of hands. Both numeric values and photos of the database, MaoBD, will be available in http://goo.gl/95s5Bz. The comparative evaluation of the methods found little disagreement among them, but the indirect method has resulted in a faster and cost-effective method for data collection that can be used to extend a database representing the Brazilian population. The length of the palm was the best parameter for estimating stature.