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The melanocortin-4 receptor (MC4R) gene harbours one of the strongest susceptibility loci for obesity and obesity-related metabolic consequences. We analysed whether dietary factors may attenuate the associations between MC4R genotypes and obesity and metabolic parameters. In 819 participants genotyped for common MC4R polymorphisms (rs17782313, rs12970134, rs633265, and rs135034), the anthropometric measurements, body fat content and distribution (visceral and subcutaneous adipose tissue, VAT and SAT, respectively), and blood glucose, insulin, total-, LDL-, HDL-cholesterol, triglycerides concentrations, and daily macronutrient intake were assessed. ANOVA or Kruskal–Wallis tests were used, and multivariate linear regression models were developed. We observed that the CC genotype carriers (rs17782313) presented higher VAT, VAT/SAT ratio, fasting blood glucose and triglyceride concentrations when they were stratified to the upper quantiles of protein intake. An increase in energy derived from proteins was associated with higher BMI (Est. 5.74, R2 = 0.12), body fat content (Est. 8.44, R2 = 0.82), VAT (Est. 32.59, R2 = 0.06), and VAT/SAT ratio (Est. 0.96, R2 = 0.05). The AA genotype carriers (rs12970134) presented higher BMI, body fat, SAT and VAT, fasting blood glucose, triglycerides and total cholesterol concentrations. An increase in energy derived from proteins by AA carriers was associated with higher VAT (Est.19.95, R2 = 0.06) and VAT/SAT ratio (Est. 0.64, R2 = 0.05). Our findings suggest that associations of the common MC4R SNPs with obesity and its metabolic complications may be dependent on the daily dietary intake, which may open new areas for developing personalised diets for preventing and treating obesity and obesity-related comorbidities.

Screening the MC4R gene showed one rare mutation p.Met215Ile in a Moroccan patient with morbid obesity, which leads to a change in the protein structure. The analysis of MC4R variants may be useful for future therapeutic approaches.

The aim of this work was to analyse the distribution of causal and candidate mutations associated to relevant productive traits in twenty local European pig breeds. Also, the potential of the SNP panel employed for elucidating the genetic structure and relationships among breeds was evaluated. Most relevant genes and mutations associated with pig morphological, productive, meat quality, reproductive and disease resistance traits were prioritized and analyzed in a maximum of 47 blood samples from each of the breeds (Alentejana, Apulo- Calabrese, Basque, Bísara, Majorcan Black, Black Slavonian (Crna slavonska), Casertana, Cinta Senese, Gascon, Iberian, Krškopolje (Krškopoljski), Lithuanian indigenous wattle, Lithuanian White Old Type, Mora Romagnola, Moravka, Nero Siciliano, Sarda, Schwäbisch-Hällisches Schwein (Swabian Hall pig), Swallow-Bellied Mangalitsa and Turopolje). We successfully analyzed allelic variation in 39 polymorphisms, located in 33 candidate genes. Results provide relevant information regarding genetic diversity and segregation of SNPs associated to production and quality traits. Coat color and morphological trait-genes that show low level of segregation, and fixed SNPs may be useful for traceability. On the other hand, we detected SNPs which may be useful for association studies as well as breeding programs. For instance, we observed predominance of alleles that might be unfavorable for disease resistance and boar taint in most breeds and segregation of many alleles involved in meat quality, fatness and growth traits. Overall, these findings provide a detailed catalogue of segregating candidate SNPs in 20 European local pig breeds that may be useful for traceability purposes, for association studies and for breeding schemes. Population genetic analyses based on these candidate genes are able to uncover some clues regarding the hidden genetic substructure of these populations, as the extreme genetic closeness between Iberian and Alentejana breeds and an uneven admixture of the breeds studied. The results are in agreement with available knowledge regarding breed history and management, although largest panels of neutral markers should be employed to get a deeper understanding of the population’s structure and relationships.

Background: Congenital leptin deficiency is a recessive genetic disorder associated with severe early-onset obesity. It is caused by mutations in the leptin (LEP) gene, which encodes the protein product leptin. These mutations may cause nonsense-mediated mRNA decay, defective secretion or the phenomenon of biologically inactive leptin, but typically lead to an absence of circulating leptin, resulting in a rare type of monogenic extreme obesity with intense hyperphagia, and serious metabolic abnormalities. Methods: We present two severely obese sisters from Colombia, members of the same lineal consanguinity. Their serum leptin was measured by MicroELISA. DNA sequencing was performed on MiSeq equipment (Illumina) of a next-generation sequencing (NGS) panel involving genes related to severe obesity, including LEP. Results: Direct sequencing of the coding region of LEP gene in the sisters revealed a novel homozygous missense mutation in exon 3 [NM_002303.3], C350G&gt, T [p.C117F]. Detailed information and clinical measurements of these sisters were also collected. Their serum leptin levels were undetectable despite their markedly elevated fat mass. Conclusions: The mutation of LEP, absence of detectable leptin, and the severe obesity found in these sisters provide the first evidence of monogenic leptin deficiency reported in the continents of North and South America.

En los últimos años se han identificado una serie de proteínas capaces de regular la conducta alimentaria y/o modular los rasgos psicopatológicos que presentan los pacientes con Trastornos de la Conducta Alimentaria (TCA). El objetivo del trabajo fue establecer si la existencia de polimorfismos en los genes BDNF, NEGR1 y MC4R, relacionados con los mecanismos de regulación de la ingesta, puede influenciar el riesgo a desarrollar un TCA y/o modular parámetros fisiológicos y psicopatológicos. Analizamos 6 polimorfismos del gen BDNF y 21 del gen NEGR1 en 169 mujeres con TCA y 312 controles sanos y la secuencia completa del gen MC4R en tres grupos (170 obesos, 77 mujeres no obesas con comportamiento por atracón diagnosticadas de Bulimina Nerviosa, BN o Trastorno por Atracón y 20 mujeres con Anorexia Nerviosa, AN). Nuestros resultados muestran que ninguno de los SNPs o haplotipos de los genes BDNF y NEGR1 influía en el riesgo de padecer un TCA. Sin embargo, el genotipo TT del SNP rs16917237 del gen BDNF se asociaba con un aumento del peso e IMC y la presencia de dos haplotipos mostraba un marcado efecto sobre las puntuaciones del cuestionario SCL-90R. En cuanto al gen NEGR1, destacó la presencia de una región central asociada con mayores puntaciones en varias escalas del cuestionario EDI-2 en pacientes con BN. Finalmente, se identificaron 10 variantes del gen MC4R en pacientes obesos y solo dos pacientes con comportamiento por atracón eran portadoras del polimorfismo I125L. Podemos concluir que ciertos polimorfismos de los genes BDNF y NEGR1 pueden tener una influencia relevante en determinados rasgos de la personalidad característicos de pacientes con TCA., In the past years, researchers have identified a number of proteins, with the ability to regulate eating behavior and/or modulate the psychopathological traits in patients with eating disorders (ED). The aim of this study was to establish whether the existence of polymorphisms in BDNF, NEGR1 and MC4R genes, involved in the neuronal control of weight may also influence in the risk to develop an ED and/or modulate physiological or psychopathological parameters. We analyzed 6 polymorphisms in BDNF and 21 in NEGR1 in 169 women with ED and 312 healthy controls and we screened the complete coding region of the MC4R gene in three groups (170 obese patients, 77 non-obese women with binge-eating behavior diagnosed with BN or Binge Eating Disorder and 20 women with AN). Our results show that none of the BDNF and NEGR1 SNPs or haplotypes were associated with a greater risk of ED. However, the TT genotype of rs16917237 BDNF SNP was associated with higher weight and BMI and two haplotypes showed a broad effect on the scores of SCL-90R test. The study of the NEGR1 gen pointed out the presence of a central region associated with higher scores in several scales of EDI-2 test in BN patients. Finally, 10 different variants of MC4R were identified in the obesity group, whilst in the binge-eating patients only two individuals with BN were found to carry the I251L polymorphism. Our results suggest that certain polymorphisms of the BDNF and NEGR1 genes could have influence in certain personality traits of ED patients.

Context: The melanocortin-4 receptor gene (MC4R) plays a pivotal role in the regulation of body fat and food and energy intake. Objectives: The objectives of the study were as follows: 1) to evaluate the association of variants rs17782313 and rs17700633 near the coding region of MC4R and 2) to evaluate the association of the transcript levels of MC4R with adiposity indices and percentage of energy from fat, carbohydrates, and protein in children. Design: The Identification and Prevention of Dietary- and Lifestyle-Induced Health Effects in Children and Infants (IDEFICS) cohort was used, with examinations at baseline (T0) and after 2 years (T1). Setting and Participants: A total of 16 228 schoolchildren (2-9 y) from eight European countries participated in the study. A random sample of 4381 children genotyped for MC4R variants and a subsample of 410 children with MC4R expression data in peripheral blood cells (PBCs) were included in the analyses. Main Outcome Measures: Anthropometric measures and energy intake (total and from fat, carbohydrates, and protein) served as outcomes for adiposity status and for dietary behavior, respectively. Results: At T0, the C allele of rs17782313 (minor frequency allele 23%) was significantly associated with higher values of adiposity indices (all P < .001). No association was found between rs17700633 (minor frequency allele 28%) and the variables under study. At T1, the C allele of rs17782313 was associated with a significantly higher increase in the adiposity indices over time (all P < .05). The MC4R expression levels in PBCs were inversely associated with body fat and energy intake from carbohydrates and directly with energy from fat (all P

The melanocortin-4 receptor (MC4R) gene codes for a G protein transmembrane receptor playing an important role in energy homeostasis control. In pig a single nucleotide polymorphism c.1426G>A has been identified and associated to average daily gain, feed intake and fatness traits but a lack of agreement on the effects of the gene on carcass traits in different breeds comes out from many studies. In the present study the c.1426G>A polymorphism is analysed in two Italian pig breeds, Large White and Duroc to study the association of the MC4R gene with some carcass traits. The results show that the c.1426G>A polymorphism affects daily gain, feed conversion ratio and ham weight in both breeds, lean cuts in the Italian Duroc and backfat thickness in the Italian Large White. The presence of MC4R mRNA transcript in different porcine tissues was analysed.

MC4R gene is known as an important candidate gene for the growth trait. The purpose of this research was to identify the MC4R gene in Kebumen Ongole grade cattle and examine its association with growth traits. D ata of birth weight (BW) , weaning weight (WW), birth body length (BBL), birth chest circumference (BCC), birth shoulder height (BSH), weaning body length (WBL), weaning chest circumference (WCC), weaning shoulder height (WSH) and average daily gain (ADG) were collected and used for analysis of MC4R gene. Sixty blood samples were collected for DNA isolation and PCR amplification. The single nucleotide polymorphisms (SNP) g.1133 C>G was used for genotyping by using PCR-RFLP methods. The frequenciy of G allele (0.59) was greater than C allele (0.41). The highest genotype frequencies have been detected in CG heterozygote animals (0.52) followed by GG (0.33) and CC (0.15) in homozygote animals. The results of Pearson ‘s Chi-square test indicated that the population was not deviate (P>0.05) from the Hardy-Weinberg equilibrium (HWE). The SNP g. 1133 C>G of MC4R gene indicated affecting high birth body length with GG genotype (P G may can be a marker for birth body length of calf selection.

Tese de doutoramento em Antropologia, na especialidade de Antropologia Biológica, apresentada ao Departamento de Ciências da Vida da Faculdade de Ciências e Tecnologia da Universidade de Coimbra The prevalence of obesity is a growing problem worldwide. Such scenario urges for additional efforts in both investment on prevention and research relating to the identification of risk factors that may aid early intervention. It is widely accepted that obesity is a complex multifactorial and heterogeneous condition with an important genetic component in the susceptibility risk. Therefore, the identification of associated gene variants could be essential in the design of prevention strategies and management of individuals genetically predisposed to obesity. In 2007, it was identified the first single nucleotide polymorphism (SNP) located in the FTO gene (rs9939609) associated with obesity by genome-wide association studies (GWAS). Until now, more than 52 genetic loci have been unequivocally associated with obesity related-traits in several European populations. However, none of these studies was performed before in a sample of Portuguese population. The main aims of this study were i) to estimate the prevalence of obesity in 6-12 years old children from the central region of Portugal; ii) to investigate whether 14 previously described SNPs in obesity-related genes are associated with the risk of obesity in Portuguese children; iii) to identify MC4R gene mutations in children with morbid obesity (BMI ≥99th) that could justify this phenotype. Anthropometric parameters such as weight, height and waist circumference were measured in a random representative sample of 1433 children (747 girls and 686 boys) between 6-12 years old from several public schools in 2011. The International Obesity Task Force (IOTF) cut-offs were used to define obesity. Children classified with overweight (320) and obesity (154), and 256 randomly selected lean subjects with 18.5T polymorphism, located in the lactase (LCT) gene, and obesity-related traits, and found indication for an association between the -13910*T allele and abdominal obesity (OR=1.41; p=0.03). Under the dominant model, significant association was observed between the LCT-13910 CT/TT genotypes and abdominal obesity (OR=1.65; p=0.02). No association was detected with the risk of obesity (p=0.35) or anthropometrics traits (p>0.05). Finally, we tested for the association of obesity-related quantitative traits in Portuguese children with ten polymorphisms in the obesity related genes MSRA, TFAP2B, MC4R, NRXN3, PPARGC1A, TMEM18, SEC16B, HOXB5 and OLFM4. The MC4R rs12970134 polymorphism was nominally associated with BMI (p=0.03), BMI Z-score (p=0.04) and waist circumference (p=0.02), and borderline associated with weight (p=0.05). Near nominal associations were also found for the PPARGC1A rs8192678 polymorphism with weight (p=0.06), and for the MSRA rs545854 polymorphism with BMI (p=0.05) and BMI Z-score (p=0.05). Furthermore, logistic regression under the additive model showed that MC4R rs12970134 and TFAP2B rs987237 were nominally, respectively, associated (OR=1.47; p=0.02) and borderline associated (OR=1.47; p=0.05) with the obese phenotype. Additionally, 32 children who present a BMI ≥99th were screened for MC4R gene mutations. We found two previously described polymorphisms at heterozygous state in two children: the -174A>C (rs34114122) polymorphism in the 5´UTR region in a girl with BMI Z-score=2.51; and the common missense mutation 307G>A (Val103Ile) in the MC4R gene coding region identified in a boy with a BMI Z-score=2.60. No other pathogenic MC4R gene mutations were detected. In conclusion, this study shows a high prevalence of overweight/obesity among Portuguese children, following the trend of other European countries. We highlighted for the first time the possible association of FTO, MC4R, PPARGC1A, MSRA and TFAP2B SNPs with several obesity-related traits in a sample of Portuguese children. FTO SNPs showed the strong association with the risk of obesity in line with previous studies performed in European populations. Our study is a significant contribution to the knowledge of the genetic basis of obesity in the Portuguese population, but further studies are needed to a better understanding of the genetic factors linked to the obesity risk. Such information could be used in the future for the development of new obesity preventive strategies. A prevalência da obesidade tem vindo a aumentar em todo o mundo. Tal cenário implica esforços adicionais no investimento tanto em matéria de prevenção como de investigação relacionados com a identificação de fatores de risco que podem ajudar a intervenção precoce. É amplamente aceite que a obesidade é uma condição multifatorial e heterogênea complexa com uma importante componente genética. Portanto, a identificação de variantes genéticas associadas poderão ser essenciais em estratégias de prevenção em indivíduos geneticamente predispostos à obesidade. Em 2007, foi identificado o primeiro polimorfismo de nucleótido simples (SNP) localizado no gene FTO (rs9939609) associado à obesidade em estudos de associação do genoma (GWAS). Mais de 52 loci genéticos foram já associados à obesidade em várias populações Europeias. No entanto, nenhum estudo do género foi até agora realizado numa amostra da população Portuguesa. Os principais objetivos deste estudo foram i) estimar a prevalência de obesidade em crianças dos 6-12 anos da região centro de Portugal; ii) investigar se 14 SNPs previamente descritos em genes relacionados com a obesidade, estão associados com o risco de obesidade em crianças portuguesas; iii) identificar mutações no gene MC4R em crianças com obesidade mórbida (IMC ≥99th) que poderão justificar o fenótipo. Os parâmetros antropométricos, tais como, peso, altura e circunferência da cintura (CC) foram medidos numa amostra aleatória de 1433 crianças (747 raparigas e 686 rapazes) entre os 6-12 anos, de várias escolas públicas em 2011. Os limites do International Obesity Task Force (IOTF) foram usados para definir obesidade. Crianças classificadas com excesso de peso (320) e obesidade (154), e 256 indivíduos normais escolhidos aleatoriamente com 18,5T, localizado no gene da lactase (LCT), e a obesidade, tendo sido encontrada indicação para uma associação entre o alelo -13910*T e a obesidade abdominal (OR=1,41; p=0,03). Sob o modelo dominante, foi observada uma associação significativa entre os genótipos CT/TT e obesidade abdominal (OR=1,65; p=0,02). Nenhuma associação foi observada com o risco de obesidade (p=0,35) ou características antropométricas (p>0,05). Finalmente, foi testada a associação de características quantitativas relacionadas com a obesidade em crianças portuguesas com dez SNPs nos genes relacionados com a obesidade MSRA, TFAP2B, MC4R, NRXN3, PPARGC1A, TMEM18, SEC16B, HOXB5 e OLFM4. O SNP MC4R rs12970134 foi encontrado nominalmente associado com IMC (p=0,03), IMC Z-score (p=0,04) e CC (p=0,02), e no limite de significância com peso (p=0,05). Foram também encontradas associações nominais para o polimorfismo PPARGC1A rs8192678 com peso (p=0,06), e para o polimorfismo MSRA rs545854 com IMC (p=0,05) e IMC Z-score (p=0,05). A regressão logística sob o modelo aditivo mostrou que os SNPs MC4R rs12970134 e TFAP2B rs987237 se encontram, nominalmente, respetivamente, associado (OR=1,47; p=0,02) e no limite de significância associado (OR=1,45; p=0,05) com o fenótipo obeso. Adicionalmente, 32 crianças que apresentavam um IMC ≥99th foram rastreadas para mutações no gene MC4R. Foram encontrados dois SNPs, previamente descritos, em heterozigotia em duas crianças: o SNP -174A>C (rs34114122) na região 5'UTR numa rapariga com IMC Z-score=2,51; e a mutação missense comum 307G>A (Val103Ile) na região codificante do gene num rapaz com um IMC Z-score=2.60. Não foram detetadas outras mutações no gene MC4R. Em conclusão, este estudo mostrou uma alta prevalência de excesso de peso/obesidade nas crianças portuguesas, seguindo a tendência de outros países europeus. Foi encontrada pela primeira vez numa amostra de crianças portuguesas, uma possível associação dos SNPs nos genes FTO, MC4R, PPARGC1A, MSRA e TFAP2B com várias medidas de obesidade. Os polimorfismos no gene FTO mostraram a associação mais forte com o risco de obesidade em linha com estudos previamente realizados em populações europeias. O nosso trabalho é uma importante contribuição para o conhecimento da base genética da obesidade na população portuguesa, mas são necessários mais estudos para melhor compreender estes fatores genéticos associados ao risco da obesidade. Esta informação poderá vir a ser usada no futuro para o desenvolvimento de novas estratégias de prevenção para a obesidade. La prevalencia de la obesidad es un problema creciente en todo el mundo. Tal escenario exige esfuerzos adicionales e inversión, tanto en materia de prevención como en investigación enfocada a la identificación de factores de riesgo que puedan ayudar a la intervención precoz. Está ampliamente aceptado que la obesidad es un complejo trastorno multifactorial y heterogéneo cuyo componente genético supone un importante factor de riesgo. Por lo tanto, la identificación de variantes genéticas asociadas podría ser esencial en el diseño de estrategias de prevención y de manejo de individuos genéticamente predispuestos a la obesidad. En 2007 se identificó el primer polimorfismo de nucleótido simple (SNP) asociado a la obesidad, localizado en el gen FTO (rs9939609), por un estudio de asociación del genoma completo (GWAS). Hasta ahora más de 52 loci genéticos han sido asociados inequívocamente a rasgos relacionados con la obesidad en varias poblaciones europeas. Sin embargo, ninguno de estos estudios se realizó antes en una muestra de población portuguesa. Los principales objetivos de este estudio fueron (i) estimar la prevalencia de la obesidad en niños de 6-12 años de edad de la región central de Portugal; (ii) investigar si 14 SNPs previamente descritos en los genes relacionados con la obesidad están asociados con el riesgo de obesidad en niños portugueses; (iii) identificar en niños con obesidad mórbida (IMC ≥ percentil 99) mutaciones en el gen MC4R que podrían justificar el fenotipo. Se midieron parámetros antropométricos tales como peso, altura y circunferencia de la cintura en una muestra aleatoria representativa de 1433 niños (747 niñas y 686 niños) de 6-12 años de varias escuelas públicas en 2011. Para definir la obesidad se utilizaron los puntos de cortes de la International Obesity Task Force (IOTF), y con ellos se seleccionaron para el genotipado 320 niños con sobrepeso, 154 con obesidad, y 256 de peso normal escogidos al azar para el grupo control de un total de 928 (18.5T, situado en el gen de la lactasa (LCT), se encontraron indicios de asociación entre el alelo -13910*T y la obesidad abdominal (OR=1,41 p=0,03). Bajo el modelo dominante, se observó una asociación significativa entre los genotipos CT/TT y la obesidad abdominal (OR=1,65 p=0,02), pero no se detectó asociación con el riesgo de obesidad (p=0,35) o con rasgos antropométricos (p>0,05). Por último, se estudiaron otros diez SNPs de genes relacionados con la obesidad (MSRA, TFAP2B, MC4R, NRXN3, PPARGC1A, TMEM18, SEC16B, HOXB5 y OLFM4). El SNP rs12970134 MC4R mostró una asociación nominal con el IMC (p=0,03), el valor Z-score (p=0,04) y la circunferencia de la cintura (p=0,02), y en el límite de significancia con el peso (p=0,05). En el límite se encuentran también las asociaciones nominales obtenidas para el SNP rs8192678 PPARGC1A con el peso (p=0,06), y para el SNP rs545854 MSRA con el IMC (p=0,05) y el IMC Z-score (p=0,05). Por otra parte, la regresión logística bajo el modelo aditivo mostró que los SNPs MC4R rs12970134 y TFAP2B rs987237, en relación con el fenotipo obeso, estaban nominalmente asociados (OR=1.47; p=0.02) y nominalmente en el límite de la asociación (OR=1.47; p=0.05), respectivamente. Además, se realizó el cribado de mutaciones del gen MC4R en los 32 niños que presentaban un IMC ≥ percentil 99. Se encontraron dos SNPs descritos anteriormente en estado heterocigoto: el polimorfismo -174A>C (rs34114122) en la región 5'UTR en una niña con IMC Z-score=2,51; y la mutación común missense 307G>A (Val103Ile) en la región codificante del gen MC4R de un niño con IMC Z-score=2,60. No se detectaron otras mutaciones patogénicas en el gen MC4R. En conclusión, este estudio muestra una alta prevalencia de sobrepeso/obesidad entre los niños portugueses, siguiendo la tendencia de otros países europeos. Además, se destaca por primera vez la posible asociación de SNPs en los genes FTO, MC4R, PPARGC1A, MSRA y TFAP2B con varios rasgos relacionados con la obesidad en una muestra de niños portugueses. Los SNPs del gen FTO mostraron una fuerte asociación con el riesgo de obesidad, en línea con estudios previos realizados en poblaciones europeas. Este trabajo es una contribución significativa al conocimiento de las bases genéticas de la obesidad en la población portuguesa, pero se necesitan más estudios para una mejor comprensión de este componente genético, lo que podría ser utilizado en el futuro para el desarrollo de nuevas estrategias preventivas frente a la obesidad. FCT - SFRH/BD/68774/2010

MC4R (melanocortin 4 receptor) is expressed in the appetite-regulating areas of the brain and takes part in leptin signaling pathways. Sequencing of the coding region of the MC4R gene for 354 yaks identified the following five single nucleotide polymorphisms (SNPs): SNP1 (273C>T), SNP2 (321 G>T), SNP3 (864 C>A), SNP4 (1069G>C) and SNP5 (1206 G>C). SNP1, SNP2 and SNP3 were synonymous mutations, whereas SNP4 and SNP5 were missense mutations resulting in amino acid substitutions (V286L and R331S). Pairwise linkage disequilibrium (LD) analysis indicated that two pairs of SNPs, SNP2 and SNP5 (r(2)=0.81027) and SNP4 and SNP5 (r(2)=0.53816), exhibited higher degrees of LD. CC genotype of SNP4, CGACG and CTCCC haplotypes for all SNPs were associated with increased BW of animals that were 18 months old and with the average daily gain. The secondary structure and transmembrane region prediction of the yak MC4R protein suggested that SNP4 was correlated with influential changes in the seventh transmembrane domain of the MC4R protein and with the functional deterioration or even incapacitation of MC4R, which may contribute to the increased feed intake, BW and average daily gain of the yaks with CC genotypes. The data from this study suggested that 1069G>C SNP of the MC4R gene could be used in marker-assisted selection of growth traits in the Maiwa yak breed.

Background: The melanocortin-4 receptor gene (MC4R) plays an important role in regulating food intake and body weight in mammals. In the present study, we identified the MC4R gene in native Korean brown, brindle, and black cattle by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP), and investigated its association with economic traits. A total of 413 cattle from the three breeds were tested for backfat thickness, carcass weight, longissimus muscle area, and marbling score, and statistical data were analyzed using the SAS program. Results: The C allele had the highest frequency in brown and brindle cattle, and the G allele frequency was highest in black cattle. The C1069G SNP was significantly (p < 0.05) associated with only marbling scores in brown and brindle cattle but no significant association was detected between the marbling scores and polymorphism in black cattle. Conclusions: These results suggest that a C1069G SNP of the MC4R gene may be useful as a genetic marker for marbling scores in Korean brown and brindle cattle.

The study presents evaluation of pig genetic markers (MHS and MC4R) associated with performance traits in the Lithuanian White pig breed. The study presents a direct approach the testing and explanation of the quantitative part of the trait and QTL with marker based on estimated breeding values in the Lithuanian White population. Information about the strategies for association analysis and improvement can be applied for further characterization of the Lithuanian White population. The use of breeding values instead of single measurements reduces the bias in the recorded performance traits, therefore, the results obtained by using the marker for the Lithuanian White population gives animal breeders the opportunities for realization of a short-term goal in their selection criteria.

Obesity is a common multifactorial disease with which environmental and genetic factors interact. Obesity is a risk factor for early mortality, metabolic and cardiovascular complications. The strongest evidence for a genetic component of human obesity is the familial clustering and the high concordance of body composition in monozygotic twins. However, the role of genetic factors in obesity is complex. The human genes which cause monogenic obesity are encoding leptin, leptin receptor, POMC and MC4R. Another common form of human obesity is poligenic. Candidate genes studies and genome-wide scans were applied in searching for genes underlying poligenic obesity in humans. As a result, the mutations which were found account for only a few parts of obese cases. More genom wide scans with a high number of polymorphic marker are needed to identify another chromosomal region in obesity. Such studies will provide significant progresses for treatment and preventive medicine of human obesity.

BACKGROUND: Single nucleotide polymorphisms (SNPs) in genes encoding the components involved in the hypothalamic pathway may influence weight gain and dietary factors may modify their effects.\ud \ud AIM: We conducted a case-cohort study to investigate the associations of SNPs in candidate genes with weight change during an average of 6.8 years of follow-up and to examine the potential effect modification by glycemic index (GI) and protein intake.\ud \ud METHODS AND FINDINGS: Participants, aged 20-60 years at baseline, came from five European countries. Cases ('weight gainers') were selected from the total eligible cohort (n = 50,293) as those with the greatest unexplained annual weight gain (n = 5,584). A random subcohort (n = 6,566) was drawn with the intention to obtain an equal number of cases and noncases (n = 5,507). We genotyped 134 SNPs that captured all common genetic variation across the 15 candidate genes; 123 met the quality control criteria. Each SNP was tested for association with the risk of being a 'weight gainer' (logistic regression models) in the case-noncase data and with weight gain (linear regression models) in the random subcohort data. After accounting for multiple testing, none of the SNPs was significantly associated with weight change. Furthermore, we observed no significant effect modification by dietary factors, except for SNP rs7180849 in the neuromedin β gene (NMB). Carriers of the minor allele had a more pronounced weight gain at a higher GI (P = 2 x 10⁻⁷).\ud \ud CONCLUSIONS: We found no evidence of association between SNPs in the studied hypothalamic genes with weight change. The interaction between GI and NMB SNP rs7180849 needs further confirmation.

Background: Adiposity traits have been associated with risk of many cancers in observational studies, but whether these associations are causal is unclear. Mendelian randomization (MR) uses genetic predictors of risk factors as instrumental variables to eliminate reverse causation and reduce confounding bias. We performed MR analyses to assess the possible causal relationship of birthweight, childhood and adult body mass index (BMI), and waist-hip ratio (WHR) on the risks of breast, ovarian, prostate, colorectal and lung cancers. Methods: We tested the association between genetic risk scores and each trait using summary statistics from published genome-wide association studies (GWAS) and from 51 537 cancer cases and 61 600 controls in the Genetic Associations and Mechanisms in Oncology (GAME-ON) Consortium. Results: We found an inverse association between the genetic score for childhood BMI and risk of breast cancer [odds ratio (OR)=0.71 per standard deviation (s.d.) increase in childhood BMI; 95% confidence interval (CI): 0.60, 0.80; P=6.5×10-5). We also found the genetic score for adult BMI to be inversely associated with breast cancer risk (OR=0.66 per s.d. increase in BMI; 95% CI: 0.57, 0.77; P=2.5×10-7), and positively associated with ovarian cancer (OR=1.35; 95% CI: 1.05, 1.72; P=0.017), lung cancer (OR=1.27; 95% CI: 1.09, 1.49; P=2.9×10-3) and colorectal cancer (OR=1.39; 95% CI: 1.06, 1.82, P=0.016). The inverse association between genetically predicted adult BMI and breast cancer risk remained even after adjusting for directional pleiotropy via MR-Egger regression. Conclusions: Findings from this study provide additional understandings of the complex relationship between adiposity and cancer risks. Our results for breast and lung cancer are particularly interesting, given previous reports of effect heterogeneity by menopausal status and smoking status. © The Author 2016; Published by Oxford University Press on behalf of the International Epidemiological Association All rights reserved.