Our knowledge of the genetic factors affecting obesity is increasing, but information about the individual gene effects remains limited in humans as well as in animal models. The melanocortin-4 receptor gene (MC4R) has been implicated in the regulation of feeding behavior and body weight in humans and mice. We have studied MC4R as a candidate gene for the control of economically important growth and performance traits in the pig. A missense mutation was identified in a region highly conserved among melanocortin receptor (MCR) genes. To determine whether there was an association of this MC4R polymorphism with phenotypic variation, we tested the mutation in a large number of individual animals from several different pig lines. Analyses of growth and performance test records showed significant associations of MC4R genotypes with backfat and growth rate in a number of lines as well as feed intake overall. It is probable that the variant amino acid residue of the MC4R mutation (or a closely linked mutation) causes a significant change of the MC4R function. These results support the functional significance of a pig MC4R missense mutation and suggest that comparative genomics based on model species may be equally important for application to farm animals as they are for human medicine.

The Pecorans (higher ruminants) are believed to have rapidly speciated in the Mid-Eocene, resulting in five distinct extant families: Antilocapridae, Giraffidae, Moschidae, Cervidae, and Bovidae. Due to the rapid radiation, the Pecoran phylogeny has proven difficult to resolve, and 11 of the 15 possible rooted phylogenies describing ancestral relationships among the Antilocapridae, Giraffidae, Cervidae, and Bovidae have each been argued as representations of the true phylogeny. Here we demonstrate that a genome-wide single nucleotide polymorphism (SNP) genotyping platform designed for one species can be used to genotype ancient DNA from an extinct species and DNA from species diverged up to 29 million years ago and that the produced genotypes can be used to resolve the phylogeny for this rapidly radiated infraorder. We used a high-throughput assay with 54,693 SNP loci developed for Bos taurus taurus to rapidly genotype 678 individuals representing 61 Pecoran species. We produced a highly resolved phylogeny for this diverse group based upon 40,843 genome-wide SNP, which is five times as many informative characters as have previously been analyzed. We also establish a method to amplify and screen genomic information from extinct species, and place Bison priscus within the Bovidae. The quality of genotype calls and the placement of samples within a wellsupported phylogeny may provide an important test for validating the fidelity and integrity of ancient samples. Finally, we constructed a phylogenomic network to accurately describe the relationships between 48 cattle breeds and facilitate inferences concerning the history of domestication and breed formation.ancient DNA ͉ Pecorans ͉ domestication

In total, 166 individuals from five indigenous Ethiopian cattle populations – Ambo (n = 27), Borana (n = 35), Arsi (n = 30), Horro (n = 36), and Danakil (n = 38) – were genotyped for 8773 single nucleotide polymorphism (SNP) markers to assess genetic diversity, population structure, and relationships. As a representative of taurine breeds, Hanwoo cattle (n = 40) were also included in the study for reference. Among Ethiopian cattle populations, the proportion of SNPs with minor allele frequencies (MAFs) ≥0.05 ranged from 81.63% in Borana to 85.30% in Ambo, with a mean of 83.96% across all populations. The Hanwoo breed showed the highest proportion of polymorphism, with MAFs ≥0.05, accounting for 95.21% of total SNPs. The mean expected heterozygosity varied from 0.370 in Danakil to 0.410 in Hanwoo. The mean genetic differentiation (FST; 1%) in Ethiopian cattle revealed that within individual variation accounted for approximately 99% of the total genetic variation. As expected, FST and Reynold genetic distance were greatest between Hanwoo and Ethiopian cattle populations, with average values of 17.62 and 18.50, respectively. The first and second principal components explained approximately 78.33% of the total variation and supported the clustering of the populations according to their historical origins. At K = 2 and 3, a considerable source of variation among cattle is the clustering of the populations into Hanwoo (taurine) and Ethiopian cattle populations. The low estimate of genetic differentiation (FST) among Ethiopian cattle populations indicated that differentiation among these populations is low, possibly owing to a common historical origin and high gene flow. Genetic distance, phylogenic tree, principal component analysis, and population structure analyses clearly differentiated the cattle population according to their historical origins, and confirmed that Ethiopian cattle populations are genetically distinct from the Hanwoo breed.

2004;12:1981-1994. Objectives: To investigate possible obesity candidate genes in regions of porcine quantitative trait loci (QTL) for fat deposition and obesity-related phenotypes. Research Methods and Procedures: Chromosome mapping and QTL analyses of obesity candidate genes were performed using DNA panels from a reference pig family. Statistical association analyses of these genes were performed for fat deposition phenotypes in several other commercial pig populations. Results: Eight candidate genes were mapped to QTL regions of pig chromosomes in this study. These candidate genes also served as anchor loci to determine homologous human chromosomal locations of pig fat deposition QTL. Preliminary analyses of relationships among polymorphisms of individual candidate genes and a variety of phenotypic measurements in a large number of pigs were performed. On the basis of available data, gene-gene interactions were also studied. Discussion: Comparative analysis of obesity-related genes in the pig is not only important for development of markerassisted selection on growth and fat deposition traits in the pig but also provides for an understanding of their genetic roles in the development of human obesity.

The polar overdominance model of inheritance was proposed to explain the non-Mendelian expression of callipyge muscular hypertrophy in sheep. The callipyge locus (CLPG) maps to the distal portion of ovine Chromosome 18 within the DLK1-GTL2 region and corresponds to human Chromosome 14q32, where uniparental disomy (UPD) of the region is associated with multiple congenital anomalies, including growth retardation and obesity. We investigated the porcine DLK1-GTL2 region in a cross of two pig breeds to determine if the callipyge polar overdominance is present in another species. Analyses of the parental origin of DLK1 polymorphism in the F2 offspring found that paternal inheritance of DLK1 allele 2 and maternal inheritance of the allele 1 was significantly associated with decreased fat deposition and increased lean muscle mass, while the opposite parental inheritance of these alleles was associated with slower prenatal and postnatal growth. These results suggest that the polar overdominance mode of inheritance is present in the pig chromosomal region that is homologous to the CLPG locus in sheep. Further study in pigs can provide important insights into understanding the molecular regulation of imprinted genes that are associated with human UPD14 and sheep callipyge phenotypes.

Sheep in Ethiopia are adapted to a wide range of environments, including extreme habitats. Elucidating their genetic diversity is critical for improving breeding strategies and mapping quantitative trait loci associated with productivity. To this end, the present study investigated the genetic diversity and population structure of five Ethiopian sheep populations exhibiting distinct phenotypes and sampled from distinct production environments, including arid lowlands and highlands. To investigate the genetic relationships in greater detail and infer population structure of Ethiopian sheep breeds at the continental and global levels, we analyzed genotypic data of selected sheep breeds from the Ovine SNP50K HapMap dataset. All Ethiopian sheep samples were genotyped with Ovine Infinium HD SNP BeadChip (600K). Mean genetic diversity ranged from 0.29 in Arsi-Bale to 0.32 in Menz sheep, while estimates of genetic differentiation among populations ranged from 0.02 to 0.07, indicating low to moderate differentiation. An analysis of molecular variance revealed that 94.62 and 5.38% of the genetic variation was attributable to differences within and among populations, respectively. Our population structure analysis revealed clustering of five Ethiopian sheep populations according to tail phenotype and geographic origin—i.e., short fat-tailed (very cool high-altitude), long fat-tailed (mid to high-altitude), and fat-rumped (arid low-altitude), with clear evidence of admixture between long fat-tailed populations. North African sheep breeds showed higher levels of within-breed diversity, but were less differentiated than breeds from Eastern and Southern Africa. When African breeds were grouped according to geographic origin (North, South, and East), statistically significant differences were detected among groups (regions). A comparison of population structure between Ethiopian and global sheep breeds showed that fat-tailed breeds from Eastern and Southern Africa clustered together, suggesting that these breeds were introduced to the African continent via the Horn and migrated further south.

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Porcine chromosome 6 (SSC6) has been reported to have QTL affecting intramuscular fat content (IMF) in multiple populations. The objective of this study was to investigate the effect of FABP3 and LEPR genetic variations as well as their mRNA expression on the IMF trait in a three-generation of Korean native pig and Yorkshire crossed animals. Several polymorphisms of the FABP3 (HinfI, HaeIII and HinfI*) were significantly associated with moisture, tenderness and flavor score (P < 0.05), and were used to construct haplotypes: haplotype 1 (-TCT-) increased the marbling and intramuscular fat content, however, haplotype 2 (-CCT-) decreased tenderness. The LEPR AvaII polymorphism showed significant association with moisture, intramuscular fat, cholesterol and flavor score (P < 0.05). The linkage analyses with six microsatellites mapped FABP3 gene in the interval between the markers Sw1129 and S0228 (Sw1129--11.7 cM--FABP3-9.1 cM--S0228), and the LEPR gene between the markers S0121 and Sw322 (S0121--7.5 cM--LEPR--28.5 cM--Sw322). QTL mapping suggested a significant QTL affecting Moisture (83 cM) and IMF (84 cM) located close to marker S0228. The gene expression results showed that in the loin muscle, both of the FABP3 and LEPR genes showed significantly higher expression in pigs with higher IMF%, however, in the backfat, only FABP3 showed differential expression between these two groups of pigs (significantly higher expression in pigs with lower IMF%) (P < 0.05). In the liver, both of these two genes did not show any difference between the high and low IMF% groups.