O sistema hormônio de crescimento (GH) / fator de crescimento insulina- símile tipo 1 (IGF-1) é o principal determinante e regulador do crescimento linear pósnatal. O GH é codificado pelo gene Growth Hormone 1 (GH1). Mutações no GH1 com efeito dominante negativo e herança autossômica dominante são as principais causas monogênicas de deficiência isolada de hormônio de crescimento (DIGH), enquanto deleções ou mutações de ponto no GH1 causam formas raras autossômicas recessivas de DIGH. No grupo de pacientes com DIGH do ambulatório de Endocrinologia do Desenvolvimento do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, foram identificadas apenas deleções em homozigose no GH1 mesmo após estudo criterioso deste gene. Esta diferença em relação aos dados descritos na literatura poderia ser justificada pelo critério diagnóstico para a DIGH adotado pelo nosso grupo, sendo utilizado pico de GH em teste de estímulo inferior a 3,3 ug/L, em contraste com os valores de corte descritos na literatura que variam de 7 a 10 ug/L. Devido a esse fator, pacientes com mutações no GH1 com herança autossômica dominante poderiam estar sendo erroneamente diagnosticados como portadores de baixa estatura familiar ou idiopática (BEI) em nosso serviço. Adicionalmente, mutações que originam moléculas de GH biologicamente inativas também poderiam estar presentes nestes pacientes. Pelos fatores acima apresentados, expandimos o estudo do GH1 para um grupo de crianças classificadas como BEI. Foram selecionadas 98 de 487 crianças avaliadas em nosso serviço com baixa estatura utilizando os seguintes critérios: peso e comprimento normais para idade gestacional ao nascimento, escore-Z da altura < -2, escore-Z do IGF-1 < -1 e pico de resposta de GH >= 3,3 ug/L no teste de estímulo. DNA foi extraído de leucócitos periféricos desses pacientes para rastreamento de mutações no gene GH1. Realizamos estudo molecular por reação em cadeia da polimerase e sequenciamento automático de toda a região codificadora do GH1. Segregação familiar foi realizada para as variantes alélicas identificadas. Em nossa casuística, foram identificadas 10 variantes alélicas nos éxons 4 e 5 e no íntron 4 do GH1, sendo três variantes ainda não descritas na literatura (c.407G > A/p.Val122Ile, c.507C > T/p.Tyr169Tyr e c.456+19G > T). A análise in silico de todas as variantes identificadas indicou ausência de predição de efeito deletério sobre a proteína do GH. Estudo complementar realizado pelo nosso grupo identificou em crianças diagnosticadas com DIGH grave apenas uma paciente com mutação no GH1 responsável pela forma dominante desta doença. Em conclusão, mutações no GH1 causadoras da forma autossômica dominante de DIGH ou Tipo II não foram encontradas em nossa casuística, o que sugere que estas mutações sejam infrequentes em nossa população / The growth hormone (GH) / insulin-like growth factor-1 (IGF-1) axis is the most important hormonal regulator of post-natal linear growth. GH is encoded by the Growth Hormone 1 gene (GH1). Mutations in GH1 with dominant inheritance, which exerts a dominant negative effect on the bioactive GH isoforms, are the main causes of monogenic isolated deficiency of growth hormone (IGHD), while deletions or point mutations in GH1 are responsible for a rare autosomal recessive form of IGHD. However, only homozygous deletions were identified in patients with IGHD from Unidade de Endocrinologia do Desenvolvimento do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, even after detailed investigation of GH1. This difference regarding to literature can be caused by different criteria used to diagnose IGHD in our group, which adopted the cutoff value of peak GH < 3.3ug/L in response to stimulation test, in contrast to literature that describes other groups that use the cutoff peak value of the 7 - 10ug/L. Consequently, patients with autosomal dominant inheritance mutations in GH1 could be being erroneously diagnosed, as having idiopathic short stature (ISS) in our group. Additionally, mutations that cause biologically inactive GH can also be responsible for short stature in these patients. Due to the factors described above, we decided to screen mutations in GH1 in a group of children classified as ISS. We selected 98 of 487 children followed in our department with short stature according to the following criteria: normal birth weight and length for gestational age, height SDS <= -2, IGF-1 SDS < -1 and peak GH in stimulation test >= 3.3 ug/L. Genomic DNA was extracted from peripheral blood leucocytes of the patients to screen for mutations in GH1. We performed molecular analysis by polymerase chain reaction and automated sequencing of the entire coding region of the GH1. Segregation analysis was performed in the presence of allelic variations. In our casuistic, we identified 10 allelic variants in exon 4, exon 5 and intron 4 of GH1, three of which have not been described (c.407G > A/p.Val122Ile, c.507C > T/p.Tyr169Tyr and c.456+19G >T). In silico analysis predicted that none of the mutant alleles would result in deleterious effect on the GH protein. An additional study in children diagnosed with severe IGHD, identified just one patient with the pathogenic GH1 mutation responsible for the dominant form of this disease. In summary, defects in GH1 responsible for the autosomal dominant form of IGHD or Type II were not found in our cohort of Brazilian patients, suggesting that these mutations are infrequent in our population

Landwirtschaftliche Systeme müssen sich immerfort an Druckfaktoren wie Klimawandel und Bevölkerungswachstum anpassen. Hierbei spielt die genetische Vielfalt von Pflanzen eine wichtige Rolle, da diese für die Sicherung der Ernährung und des Einkommens von entscheidender Bedeutung ist. Dennoch wird der wirtschaftliche Wert pflanzengenetischer Ressourcen selten untersucht. Um diese Forschungslücke zu schließen, werden in dieser Arbeit drei Bewertungen vorgestellt, welche die wirtschaftlichen Werte pflanzengenetischer Ressourcen untersuchen. Im Rahmen dieser Dissertation werden zwei verschiedene Agrarsystemen analysiert. Diese unterscheiden sich hinsichtlich des Klimas, der agrarökologischen Bedingungen, der landwirtschaftlichen Praxis, der politischen und ökonomischen Rahmenbedingungen sowie der soziokulturellen Verankerung der Kulturart. Die ersten beiden Analysen befassen sich mit der Züchtung und Produktion von Winterweizen in Deutschland. Charakterisiert sind diese durch ein gemäßigtes Klima und intensive Anbaubedingungen. In diesem System überwiegen moderne Sorten, die in einem formalisierten Züchtungsprozess entstanden sind. Es werden die folgenden Forschungsfragen beantwortet: 1) Was ist der ökonomische Wert, der durch den Austausch von Zuchtmaterial entsteht? und 2) Wie hoch ist der mikroökonomische Wert von Resistenzzüchtung? In der dritten Analyse wird ein weiteres Agrarsystem vorgestellt: Die Andenlandwirtschaft, wo im Hochland unter extensiven Bedingungen eine Vielzahl von Kartoffellandrassen angebaut wird. Dort wird folgende Frage analysiert: 3) Welche Mehrwerte wurden durch die Repatriierung oder Neuverteilung von Kartoffellandrassen erzielt? Diese Analysen zeigen, dass die Verfügbarkeit, der Austausch und die Nutzung von pflanzengenetischen Ressourcen die Agrarproduktion verbessern; es entstehen sowohl sektorale, mikroökonomische als auch ernährungsbezogene und kulturelle Mehrwerte. / Agricultural systems must constantly adapt to pressuring events such as climate change and population growth to maintain and improve production processes in a sustainable manner. Thereby the genetic diversity of plants used in agriculture constitute a strategic asset. Nevertheless, their economic value is often overlooked. To fill this research gap, this thesis presents three assessments that produce more evidence on the economic value of plant genetic resources. Two very distinct agricultural systems are discussed. These differ greatly in terms of climate, agroecological conditions, farming practices, seed systems, political and economic frameworks, and the socio-cultural embeddedness of the crop in question. The first two assessments are concerned with winter wheat (Triticum aestivum) breeding and production in the temperate climate and intensive growing conditions in Germany. Modern cultivars created in a formalized breeding process prevail in this system. The following two research questions are elaborated: 1) What is the economic value of exchanging breeding material? and 2) What is the microeconomic value of resistance breeding? The third assessment presents a different agricultural system: Andean agriculture, where a wide variety of potato landraces (Solanum spp.) are grown extensively in the Peruvian highlands. In this case, the research question I investigated is: 3) What are the benefits of repatriating (i.e., redistributing) potato landraces to Andean farmers? These studies demonstrate that the availability, exchange, and adoption of plant genetic resources, which are well adapted to and culturally embedded in specific agricultural systems, improve the overall quantity and sustainability of agricultural production. These improvements can be translated into sectoral, microeconomic as well as nutritional and cultural benefits.