No / WHO advice suggests a family-centred approach for managing the elevated risk of recessively inherited disorders in consanguineous communities, whilst emerging policy recommends community engagement as an integral component of genetic service development. This paper explores the feasibility of the family-centred approach in the UK Pakistani origin community. The study took place within a context of debate in the media, professional and lay circles about cousin marriage causing disability in children. Using qualitative methods, a total of six single-sex focus group discussions (n = 50) were conducted in three UK cities with a high settlement of people of Pakistani origin. Tape-recorded transcripts were analysed using framework analysis. Kinship networks within Pakistani origin communities are being sustained and marriage between close blood relatives continues to take place alongside other marriage options. Study participants were critical of what was perceived as a prevalent notion that cousin marriage causes disability in children. They were willing to discuss cousin marriage and disability, share genetic information and engage with genetic issues. A desire for accurate information and a public informed about genetic issues was articulated whilst ineffective communication of genetic risk information undermined professionals in their support role. This study suggests a community that is embracing change, one in which kinship networks are still active and genetic information exchange is taking place. At the community level, these are conditions supportive of the family-centred approach to genetic testing and counselling.

Yes / In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (FROH) for >1.4 million individuals, we show that FROH is significantly associated (p < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: FROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44–66%] in the odds of having children. Finally, the effects of FROH are confirmed within full-sibling pairs, where the variation in FROH is independent of all environmental confounding.

This thesis aims to understand the sociocultural aspects of the practice of consanguinity and the implications for healthcare. Consanguinity refers to intra-familial marriage and is commonly used to refer to cousin marriage. While consanguinity remains a global phenomenon, in the recent past, it has mostly been associated with non-Western populations, and has become a taboo in Western culture. Consanguinity is linked with negative health outcomes, mostly due to genetic disorders, although the extent of this link remains debatable. In the UK, consanguinity is linked mostly with the Pakistani community, which also have an overrepresentation of children with genetic disorders. In Luton, local health reports have suggested that consanguinity in the large Pakistani community plays a role in increased infant deaths. This makes Luton and the local Pakistani community, ideally placed for understanding the practice of consanguinity and the implications for healthcare. This thesis is conceptually grounded within a constructionist approach to understanding consanguinity with a critical analysis based on theories of discourse and power and knowledge. A qualitative research design was employed using an instrumental case study approach which focused on understanding consanguinity through Luton’s Pakistani community. Three main sample groups were selected, members of the Pakistani community who are not married to their cousins and are defined as lay members in this research, members of the Pakistani community in consanguineous marriages, and local service providers (primary and secondary care).

Thesis (J.C.D.)--Catholic University of America, 1934. / Bibliography: (p. [107]-113) and index.

Submitted by Leonardo Cavalcante (leo.ocavalcante@gmail.com) on 2018-04-23T22:50:06Z No. of bitstreams: 1 Arquivototal.pdf: 7015058 bytes, checksum: 0d8c1dd0bc2f42ab36a2d917f1dc6a05 (MD5) / Made available in DSpace on 2018-04-23T22:50:06Z (GMT). No. of bitstreams: 1 Arquivototal.pdf: 7015058 bytes, checksum: 0d8c1dd0bc2f42ab36a2d917f1dc6a05 (MD5) Previous issue date: 2015-07-06 / A part of the populations in Northeastern Brazil are relatively isolated geographically and these populations maintain the tradition of consanguineous marriages for generations. These two factors (isolation and inbreeding) increase the risk of birth of people with autosomal recessive intellectual disabilities. The objective of this study was to determine the genetic causes of intellectual disabilities in two large consanguineous families of Paraiba backlands. In 2012, we conducted an epidemiological study to investigate the contribution of genetic factors in determining the deficiencies in six municipalities of Paraíba previously selected by presenting high consanguinity rate. Families who had patients with neurodegenerative disorders and/or intellectual disabilities (ID) were invited by community health agents for a first screening realized by biologists in order to select patients with deficiency probably caused by genetic mutations. In total, 276 patients were screened, of which, 109 were selected for medical evaluation with neurologists. After medical evaluation, two families with multiple affected individuals in two different forms of autosomal recessive intellectual disability were selected for clinical and genetic research. We performed the linkage study using SNPs array analysis to determine homozygous regions. Subsequently, the whole exome sequencing (WES) of one affected individual of each family was sequenciated. Potentially deleterious variants detected in regions of homozigosity-by descent which were not present in Brazilian population controls or in exomes of global online databases were subject to further scrutiny and segregation analysis by Sanger sequencing. Family A has seven adult siblings with syndromic ID. Phenotype includes tall forehead, prognatism, prominent chin, very large and overhanging nose tip. Homozigosity-by-descent analysis found a 4.0 Mb region in 19q13.32-q13.33 (lod score: 3.24). WES disclosed a homozygous variant (c.418C>T, p.Arg140Trp) in mediator complex subunit 25 (MED25), predicted as deleterious by Provean, Mutation Taster, PolyPhen-2 and SIFT. MED25 is a component of the Mediator complex, involved in regulation of transcription of nearly all RNA polymerase II-dependent genes. Deleterious mutations in MED12, MED17, MED23 and recently after our publication another mutation in the MED25 have been associated with ID. Family B has nine affected adults descending from four closely related first-cousin couples affected by severe non-syndromic ID. Homozigosity-by-descent analysis disclosed a 20.7 Mb region in 8q12.3-q21.2 (lod score: 3.11). WES identified a homozygous deleterious variant in inositol monophosphatase1 gene (IMPA1), consisting of a 5 bp duplication (c.489_493dupGGGCT) leading to frameshift (p.Ser165Trpfs*10). IMPA1 gene product is responsible for the final step of biotransformation of inositol triphosphate and diacylglycerol, two second messengers, and up to now, despite its many physiological functions, no clinical phenotype has been assigned to this gene dysfunction. From this study, it was possible to develop diagnostic test by restriction enzyme and therapeutic perspective for cases associated with IMPA1. / Uma parte das populações do Nordeste brasileiro está relativamente isolada geograficamente e mantêm, há várias gerações, a tradição de casamentos consanguíneos. Esses dois fatores associados (isolamento e endocruzamento) elevam o risco de nascimento de pessoas com deficiência intelectual com herança genética autossômica recessiva. O objetivo deste trabalho foi determinar as causas genéticas da deficiência intelectual em duas grandes famílias consanguíneas do sertão paraibano. Em 2012, nosso grupo de pesquisa realizou um estudo epidemiológico para determinar a contribuição de fatores genéticos na determinação das deficiências em seis municípios do sertão paraibano selecionados previamente por apresentarem elevada taxa de consanguinidade. As famílias que apresentavam repetições de indivíduos com doenças neurodegenerativas e/ou deficiência intelectual (DI) foram convocadas pelos agentes comunitários de saúde para uma primeira triagem, realizada pelos biólogos geneticistas, a fim de selecionar pacientes que apresentavam deficiência por prováveis causas genéticas. No total, foram triados 276 pacientes, sendo que, 109 foram selecionados para avaliação médica com neurologistas. Após a avaliação médica, duas famílias com múltiplos indivíduos acometidos por duas diferentes formas de DI de herança autossômica recessiva foram selecionadas para investigação clínico-genética. O estudo de ligação para determinar regiões em homozigose foi realizado com o uso da técnica de array de SNPs. Posteriormente, foi feito o sequenciamento do exoma completo de um indivíduo afetado de cada família. Variantes potencialmente deletérias detectadas em regiões em homozigose e que não estavam presentes em controles brasileiros e em banco de dados mundiais, foram objetos de uma análise mais aprofundada e feito a análise de co-segregação através do sequenciamento de Sanger. A primeira família estudada, a família A, possui sete adultos com DI sindrômica. O fenótipo inclui testa alta, prognatismo, queixo proeminente e ponta do nariz saliente, além da DI grave. O estudo de ligação apontou duas regiões com LOD scores máximos = 3,234, uma região de 26 Mb no cromossomo 2 (2p12 - q11.2) e uma região de 4,0 Mb no cromossomo 19 (19q13.32 - q13.33). O sequenciamento do exoma revelou uma variante em homozigose (c.418C>T, p.Arg140Trp) no gene MED25 (subunidade 25 do complexo mediador), predita como deletéria por diferentes softwares (Polyphen, Provean, Mutation Taster e SIFT). O complexo mediador está envolvido na regulação da transcrição de quase todos os genes dependentes da RNA polimerase II. Mutações deletérias nos genes MED12, MED17, MED23 e, recentemente, outra mutação no MED25, têm sido associadas com DI. Já a segunda família estudada, a família B, possui nove adultos afetados, descendentes de quatro relações consanguíneas entre primos de primeiro grau, com DI grave não-sindrômica. O estudo de ligação apontou uma região de 20,7 Mb no cromossomo 8 (8q12.3-q21.2) com LOD score = 3,11. O sequenciamento do exoma identificou uma variante deletéria em homozigose no gene inositol monofosfatase1 (IMPA1), que consiste em uma duplicação de 5 pares de bases (c.489_483dupGGGCT), levando a uma mutação do tipo frameshift (p.Ser165Trpfs*10). O produto do gene IMPA1 é uma enzima responsável pela etapa final da biotransformação dos segundos mensageiros inositol trifosfato e diacilglicerol, e até o momento, apesar de apresentar importantes funções fisiológicas, não havia fenótipo clínico atribuído a esse gene. A partir deste estudo, foi possível desenvolver teste diagnóstico com triagem por enzima de restrição e perspectiva de tratamento terapêutico para os casos associados ao IMPA1.

Made available in DSpace on 2015-03-26T13:47:15Z (GMT). No. of bitstreams: 1 texto completo.pdf: 1735193 bytes, checksum: e3475200b7337e8ee03abe701c637829 (MD5) Previous issue date: 2013-04-02 / With this study aimed to determine the age at puberty of heifers and bulls Gir created field (a semi-extensive) and the relation of body measurements, ultrasound, testicular and andrologic with reproductive events in system management conditions semi-extensive. A group of 115 animals, including 66 females and 49 males, pure origin and genealogical register, aged between 14 and 24 months. Reviews and gynecological andrologic were carried out fortnightly and monthly, respectively, on a cattle ranch Elite Gir located in São Pedro dos Ferros, the state of Minas Gerais, in the period from July to November 2012. The records of the animals used for the assessments were provided by the Brazilian Agricultural Research Corporation - National Research Center for Dairy Cattle (Embrapa CNPGL) - Juiz de Fora-MG and the Brazilian Association of Breeders of Gir Dairy (ABCGIL) - Uberaba-MG. To study the variation observed in reproductive variables measured, variance analysis was performed using the statistical procedures available in using SAS ® (SAS, 2009). The animals were evaluated between the ages of 14 to 24 months, females evaluated between 9.1% (6/66 heifers) were pubescent, while in males 69.4% (34/49) were classified as pubescent. / Com presente estudo objetivou-se determinar a idade à puberdade de novilhas e tourinhos da raça Gir criados a campo (regime semi-extensivo) e verificar a relação das mensurações corporais, ultrassonográficas, testiculares e andrológicas com os eventos reprodutivos em condições de manejo do sistema semi-extensivo. Foram avaliados 115 animais, sendo 66 fêmeas e 49 machos, puros de origem e com registro genealógico, com idade entre 14 e 24 meses. Avaliações ginecológicas e andrológicas foram realizadas quinzenalmente e mensalmente, respectivamente, em uma fazenda de gado elite da raça Gir localizada no município de São Pedro dos Ferros,interior do estado de Minas Gerais, no período de julho a novembro de 2012. Os registros dos animais utilizados para as avaliações foram cedidos pela Empresa Brasileira de Pesquisa Agropecuária Centro Nacional de Pesquisa em Gado de Leite (Embrapa CNPGL) Juiz de Fora- M.G. e Associação Brasileira de Criadores da Raça Gir Leiteiro (ABCGIL) Uberaba-MG. Para estudo da variação observada nas variáveis reprodutivas aferidas, foi realizada análise variância, usando os procedimentos estatísticos disponíveis no pacote computacional SAS® (SAS, 2009). Os animais forma avaliados entre as idades de 14 a 24 meses, entre fêmeas avaliadas 9,1% (6/66 novilhas) apresentaram-se púberes, enquanto nos machos 69,4% (34/49) foram classificados como púberes.

Submitted by (edna.saturno@ufrpe.br) on 2017-04-10T15:04:57Z No. of bitstreams: 1 Eulalia Alves Barros.pdf: 223041 bytes, checksum: 40e55d9d4006393aa969756a6bf6835a (MD5) / Made available in DSpace on 2017-04-10T15:04:57Z (GMT). No. of bitstreams: 1 Eulalia Alves Barros.pdf: 223041 bytes, checksum: 40e55d9d4006393aa969756a6bf6835a (MD5) Previous issue date: 2009-02-26 / Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPq / Marota breed goats is part of the Brazilian genetic patrimony, consisting by animals highly adapted to semi-arid region. This study evaluated genetic structure of Marota breed from Embrapa Meio Norte nucleus for conservation. Pedigree records of 663 animals, which were born from 1995 to 2003, were used for population parameters estimation. Inbreeding coefficient ( F ) and average relationship coefficient (AR) of the population was 0.11% and 0.84% respectively. Generation interval (IEG) was 5.28 years and average effective size ( e N ) per generation was 222 animals; the effective number of founder animals ( e f ) and ancestral ( a f ) was the sam (48). Among 214 ancestors evaluated, just 22 of them were responsible for 50% of the population genetic variability,which indicate loss of original genes. This study shows low contribution of the founder animals among the generations. Wright inbreeding coefficient indicates population subdivision in lineages. Inbreeding and average relationship coefficients (AR) were low. / A raça caprina Marota é parte do patrimônio genético do Brasil, formada por animais altamente adaptados ao semi-árido nordestino. Neste estudo avaliouse a estrutura genética do núcleo de conservação da raça Marota, mantida pela Embrapa Meio Norte. Foram estimados os parâmetros populacionais com dados genealógicos de 663 animais nascidos entre os anos de 1995 a 2003. O coeficiente de parentesco médio (AR) e de consanguinidade ( F ) para a população foram de 0,11% e de 0,84%, respectivamente. O intervalo de gerações (IEG) foi de 5,28 anos e o tamanho efetivo médio ( e N ) por geração foi de 222 animais, sendo que o número efetivo de animais fundadores ( e f ) e de ancestrais ( a f ) foi igual (48). Dentre os 214 ancestrais, apenas 22 foram responsáveis por 50% da variabilidade genética da população, o que indica perda de genes de origem. Observa-se baixa contribuição dos animais fundadores ao longo das gerações. Os valores do coeficiente de endogamia de Wright indicam subdivisão da população em linhagens. Em geral, a consangüinidade e os valores médios do coeficiente de parentesco foram baixos.

Mémoire (M.Sc.)-- Université du Québec à Chicoutimi, 1992. / "Mémoire présenté pour l'obtention du grade de maître es sciences (M.Sc.)" Ce mémoire a été réalisé à l'UQAC dans le cadre du programme de maîtrise en médecine expérimentale de l'Un. Laval extensionné à l'UQAC. CaQCU CaQCU Bibliogr.: f. 61-68. Document électronique également accessible en format PDF. CaQCU

Made available in DSpace on 2015-03-26T13:54:51Z (GMT). No. of bitstreams: 1 texto completo.pdf: 225296 bytes, checksum: d002b20836b6d51ee31c358241176510 (MD5) Previous issue date: 2009-02-13 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / A total of 17,985 animals, within 8,746 quails from UFV1 strain and 9,239 from UFV2 strain, belonging to the Poultry Breeding Program of UFV were used to evaluate the effect of inbreeding on body weight characteristics at 28 and 42 days of age and egg production. The MTDFNRM (Multiple Trait Derivative Free Numerator Relationship Matrix) software, a system component of MTDFREML (Boldman et al., 1995), was used to process the records of the quails in numerical codes, so the identification number of the quail was always greater than the identification number of their parents, and to obtain the coefficient of inbreeding of it quail. The complete pedigree file was used to analyze the genetic structure of the population by mean of ENDOG v. 4.5 software (Gutiérrez and GOYACHE, 2008). The UFV1 strain showed an average F of 0.54%, anaverage relationship coefficient of 1.27% and 0.25% of increment or new inbreeding. The percentage of inbred this strain was 30.85% with an average F of 1.73%, ranging from 0.1% to 26.6%. The effective population size was 200.38 quails. The UFV2 strain showed an average F of 0.76%, an average relationship coefficient of 1.83% and 0.30% of increment or new inbreeding. The percentage of inbred quails for this strain was 45.54%, with an average F of 1.67%, ranging from 0.1% to 25.8%. The effective population size was 164.42. Inbreeding did not affect body weight at 28 and 42 days and egg production. The UFV genetic group 2 showed a lower effective population size, larger increment or new inbreeding, smaller effective population size than UFV1, requiring more accurate control in mating of the selected quails. / Foram utilizados dois grupos genéticos de codornas da subespécie Coturnix coturnix coturnix, totalizando 17985 aves, sendo 8746 da linhagem UFV1 e 9239 da linhagem UFV2, pertencentes ao Programa de Melhoramento de Codornas da Universidade Federal de Viçosa, com o objetivo de avaliar o efeito da endogamia nas características peso corporal das aves aos 28 e 42 dias de idade e produção de ovos. Utilizou-se o programa computacional MTDFNRM ("Multiple Trait Derivative Free Numerator Relationship Matrix"), componente do sistema MTDFREML (Boldman ET AL., 1995) para transformação dos registros dos animais em códigos numéricos, de modo que o número do animal sempre fosse maior que o número dos pais, e obter o coeficiente de endogamia das aves. O arquivo de pedigree completo foi utilizado para análise da estrutura genética da população, executada pelo programa ENDOG v. 4.5 (Gutiérrez E Goyache, 2008). O Grupo Genético UFV 1 apresentou um F médio de 0,54%, coeficiente de relação médio de 1,27% e 0,25% de incremento de endogamia. Do total de animais, 30,85% são endogâmicos, com um F médio de 1,73%, variando de 0,1% a 26,6 %. O tamanho efetivo encontrado foi de 200,38. O Grupo Genético UFV 2 apresentou um F médio de 0,76%, coeficiente de relação médio de 1,83% e 0,30% de incremento de endogamia. Do total de animais, 45,54% são endogâmicos, com um F médio de 1,67%, variando de 0,1% e 25,8 %. O tamanho efetivo encontradofoi de 164,42. A endogamia não influenciou nenhuma das características estudadas (peso corporal aos 28 e 42 dias e produção de ovos). O Grupo Genético UFV 2 apresentou menor tamanho efetivo, maior incremento de endogamia , menor número efetivo de fundadores e de ancestrais do que o UFV 1, requerendo maior controle nos acasalamentos das codornas selecionadas para reprodução.

Orientador: Ricardo da Fonseca / Resumo: As raças ovinas deslanadas são parte do patrimônio genético do Brasil, formado por animais adaptados ao semiárido nordestino e com potencial de produção de carne e pele. No entanto tratam-se de raças de recente formação, ainda com poucos programas de melhoramento genético, e consequentemente, carente de estudos da estrutura populacional, variabilidade genética, endogamia e grau de conservação. Diante disso este trabalho teve dois objetivos: 1) analisar a variabilidade genética da raça Santa Inês no Brasil com base em informações de pedigree utilizando registros de animais da raça Santa Inês, provenientes da Associação Sergipana de Criadores de Caprinos e Ovinos (ASCCO) criados na Região Nordeste do Brasil e 2) avaliar a estrutura genética e variabilidade genética do núcleo de conservação da Embrapa Caprinos e Ovinos, localizada na cidade de Sobral, região do norte do estado do Ceará, controlado pelo Sistema de Gerenciamento de rebanho (SGR) dentro do dentro do programa de melhoramento genético de caprinos e ovinos de corte – GENECOC®. O arquivo de pedigree da raça Santa Inês (ASCCO) continha 29080 animais e os arquivos de dados genealógicos pertencentes ao GENECOC 904 indivíduos da raça Santa Inês, 972 indivíduos da raça Somalis e 1372 indivíduos da raça Morada Nova. Para a primeira análise dos animais Santa Inês a média da integridade do pedigree nas últimas quatro gerações foi maior que 50% e o número de gerações completas equivalente foi igual a 4,89. O valor do coeficient... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The wooless sheep breeds are part of the genetic heritage of Brazil, formed by animals highly adapted to semi-arid Northeast and high capacity of production of meat and skin. However it is of recent formation breeds, still few breeding programs, and consequently lacking in studies of population structure, genetic variability, inbreeding and degree of conservation. Therefore this study had two objectives: 1) to analyze the genetic variability of Santa Ines in Brazil based on pedigree information using animal records Santa Ines, from the Goat Breeders of Sergipana Association and Sheep (ASCCO) created in Northeast of Brazil and 2) evaluate the genetic structure and genetic variability conservation nucleus of Embrapa goats and sheep, located in Sobral, northern region of the state of Ceará, compiled by Management System for Livestock, part of the within the Breeding Program of Goats and sheep - GENECOC® . Santa Inês breed pedigree file (ASCCO) contained 29080 animals and genealogical data files belonging to GENECOC 904 individuals Santa Ines, 972 individuals of Somalis breed and 1372 individuals of Morada Nova breed. For the first analysis of animal Santa Inês the average pedigree integrity in the last four generations was greater than 50% and the number of full generations equivalent was equal to 4.89. The value of endogamic coefficient (F) was 0.32% and the obtained relationship coefficient was 3.1%. The generation interval was 5.75 years. For the results of the parameters bas... (Complete abstract click electronic access below) / Mestre