Consequences of Postnatally Elevated Insulin-Like Growth Factor-II in Transgenic Mice: Endocrine Changes and Effects on Body and Organ Growth.

Insulin-like growth factor-II (IGF-II) is an important regulator of embryonic growth and differentiation, but its function in postnatal life is unclear. To address this point, we generated transgenic mice harboring fusion genes in which a human IGF-II complementary DNA is placed under the transcriptional control of the rat phosphoenolpyruvate carboxykinase promoter. Transgene-specific messenger RNA was detected in liver, kidney, and several parts of the gut. Serum IGF-II levels in transgenic mice were 2-3 times higher than those in controls and increased after starvation. Circulating IGF-I correlated negatively and IGF-binding protein-2 (IGFBP-2) positively with IGF-II levels, suggesting that IGF-I is displaced from IGFBPs by IGF-II and that IGFII is a major regulator of IGFBP-2. Serum levels of IGFBP-3 and IGFBP-4 tended to be higher in phosphoenolpyruvate carboxykinase- IGF-II transgenic mice than in controls, as evaluated by ligand blot analysis. Starvation reduced serum IGF-I, but increased IGFBP-2 in transgenic mice more markedly than in controls. Fasting insulin levels were significantly reduced in transgenic mice, whereas glucose levels were not influenced by elevated IGF-II. The body growth of 4- and 12- week-old mice was not significantly influenced by elevated IGF-II, but transgenic mice displayed increased kidney and testis weight at the age of 4 weeks, and increased adrenal weight at the age of 12 weeks. Our results demonstrate that elevated IGF-II in postnatal life has multiple endocrine consequences and subtle time-specific effects on organ growth

Developmental and tissue-specific expression of the Q5k gene

Expression of the Q5k gene was examined by northern blot analysis and polymerase chain reaction (PCR) in the AKR mouse and various cell lines, each of the H-2k haplotype. Our results show that Q5k mRNA is present during the whole postimplantational development of the AKR embryo/fetus (gestation day 6 to 15). In the juvenile mouse (week 2 to 4) transcription of the Q5k gene persisted in all organs examined. In contrast, in the adult animal expression of the Q5k gene was limited to the thymus and uterus of the pregnant mouse. Upon malignant transformation, the amount of Q5k-specific mRNA increased dramatically in thymus and could also be observed in the spleen of thymoma bearing animals. Expression of the Q5k gene was also detectable in several transformed mouse cell lines. Mitogen stimulation or treatment with cytokines induced Q5k expression in primary spleen cell cultures. A possible explanation for the tissue-restricted expression in the adult AKR mouse is discussed

A splice variant in KRT71 is associated with curly coat phenotype of Selkirk Rex cats.

One of the salient features of the domestic cat is the aesthetics of its fur. The Selkirk Rex breed is defined by an autosomal dominant woolly rexoid hair (ADWH) abnormality that is characterized by tightly curled hair shafts. A genome-wide case - control association study was conducted using 9 curly coated Selkirk Rex and 29 controls, including straight-coated Selkirk Rex, British Shorthair and Persian, to localize the Selkirk autosomal dominant rexoid locus (SADRE). Although the control cats were from different breed lineages, they share recent breeding histories and were validated as controls by Bayesian clustering, multi-dimensional scaling and genomic inflation. A significant association was found on cat chromosome B4 (Praw = 2.87 × 10(-11)), and a unique haplotype spanning ~600 Kb was found in all the curly coated cats. Direct sequencing of four candidate genes revealed a splice site variant within the KRT71 gene associated with the hair abnormality in Selkirk Rex

History of Lipizzan horse maternal lines as revealed by mtDNA analysis

Sequencing of the mtDNA control region (385 or 695 bp) of 212 Lipizzans from eight studs revealed 37 haplotypes. Distribution of haplotypes among studs was biased, including many private haplotypes but only one haplotype was present in all the studs. According to historical data, numerous Lipizzan maternal lines originating from founder mares of different breeds have been established during the breed's history, so the broad genetic base of the Lipizzan maternal lines was expected. A comparison of Lipizzan sequences with 136 sequences of domestic- and wild-horses from GenBank showed a clustering of Lipizzan haplotypes in the majority of haplotype subgroups present in other domestic horses. We assume that haplotypes identical to haplotypes of early domesticated horses can be found in several Lipizzan maternal lines as well as in other breeds. Therefore, domestic horses could arise either from a single large population or from several populations provided there were strong migrations during the early phase after domestication. A comparison of Lipizzan haplotypes with 56 maternal lines (according to the pedigrees) showed a disagreement of biological parentage with pedigree data for at least 11% of the Lipizzans. A distribution of haplotype-frequencies was unequal (0.2%–26%), mainly due to pedigree errors and haplotype sharing among founder mares

A microsatellite-based multilocus phylogeny of the Drosophila melanogaster species complex

AbstractUncovering the genealogy of closely related species remains a major challenge for phylogenetic reconstruction. It is unlikely that the phylogeny of a single gene will represent the phylogeny of a species as a whole [1], but DNA sequence data across a large number of loci can be combined in order to obtain a consensus tree [2]. Long sequences are needed, however, to minimize the effect of (infrequent) base substitutions, and sufficient individuals must be sequenced per species to account for intraspecific polymorphisms, an overwhelming task using current DNA sequencing technology. By contrast, microsatellites are easy to type [3], allowing the analysis of many loci in multiple individuals. Despite their successful use in mapping [4,5], behavioural ecology [6] and population genetics [7], their usefulness for the phylogenetic reconstruction of closely related taxa has never been demonstrated, even though microsatellites are often conserved across species [8–10]. One drawback to microsatellite use is their high mutation rate (10−4–10−2), combined with an incomplete understanding of their mutation patterns. Many microsatellites are available for Drosophila melanogaster, and they are distributed throughout the genome [11]. Most can be amplified in the D. melanogaster species complex [12,13] and have low mutation rates [14,15]. We show that microsatellite-specific distance measurements [16] correlate with other multilocus distances, such as those obtained from DNA–DNA hybridization data. Thus microsatellites may provide an ideal tool for building multilocus phylogenies. Our phylogenetic reconstruction of the D. melanogaster complex provides strong evidence that D. sechellia arose first, followed by a split between D. simulans and D. mauritiana

Known loci in the KIT and TYR genes do not explain the depigmented white coat colour of Austro-Hungarian Baroque donkey

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Povezanost inbreedinga i melanoma kod lipicanskih konja

The relationship between inbreeding and melanoma status (graded from 0 to 4) was analysed by various regression models. Analysed data referred to 296 grey Lipizzan horses originating from five state-owned studs (Austria, Croatia, Hungary, Slovakia and Slovenia) and with average inbreeding coefficient (F=0.107) calculated from extremely informative pedigrees (98% and 76% of horses had completely full pedigree in generation 10 and 20, respectively). In all regression models, in addition, the effects of stud (fixed) and age (covariate) were included. When all data were treated as one population, the estimates from linear and ancestral inbreeding models were not significant. Total inbreeding effect estimates (at F=0.125 and Fa=0.57) were 0.26 and 0.30 for the ancestral inbreeding and linear regression models, respectively. Heterogeneity among state-owned studs in inbreeding effects was also tested for both models and weak statistical significance was obtained for the interaction model with ancestral inbreeding (P=0.049). However, observed effect in the model with interaction was not consistent, did not yield in better model fitting and the obtained significance is probably just a statistical artefact. In general, although some indications about the relationship between ancestral inbreeding and melanoma were present, inbreeding does not appear to be a factor that substantially influences the expression of melanoma in Lipizzan horses.Regresijskim modelima analizirana je povezanost stadija melanoma (na skali od 0 do 4) i inbreedinga. Analizirani podaci odnose se na 296 sivih lipicanskih konja iz pet državnih ergela (Austrija, Hrvatska, Mađarska, Slovačka i Slovenija). Prosječna razina inbreedinga (F=0.107) izračunata je na temelju izuzetno informativnog pedigreea (98% jedinki imalo je potpuno poznat pedigre u generaciji 10, a 76% jedinki imalo je potpuno poznat pedigree u generaciji 20). U svim modelima uvažen je i utjecaj ergele (fiksni utjecaj) te starosti konja (kovarijabla). Kada se analiza koeficijenta regresije (regresija stadija melanoma na koeficijent inbreedinga) odnosila na populaciju kao jednu cjelinu, procjena linearnog koeficijenta regresije za inbreeding kao i za inbreeding predaka nije bila signifikantna. Kod razine inbreedinga F=0.125 i Fa=0.57, ukupna procjena linearnog utjecaja inbreedinga bila je 0.30, a utjecaja inbreedinga predaka bila je 0.26. Analizirana je i heterogenost utjecaja inbreedinga između državnih ergela i za interakcijski model sa inbreedingom predaka dobivena je slaba signifikantna interakcija (P=0.049). Ipak, dobiveni utjecaj u model sa interakcijom nije bio konzistentan, nije bolje objašnjavao nerazjašnjenu varijabilnost modela te je dobivena signifikantnost vjerojatno posljedica slučajnosti. Iz navedenog se može zaključiti, premda postoji indicija o povezanosti inbreedinga predaka i melanoma, da kod lipicanskih konja inbreeding nije čimbenik koji utječe na pojavu melanoma

Detection of two non-synonymous SNPs in SLC45A2 on BTA20 as candidate causal mutations for oculocutaneous albinism in Braunvieh cattle

Background: Cases of albinism have been reported in several species including cattle. So far, research has identified many genes that are involved in this eye-catching phenotype. Thus, when two paternal Braunvieh half-sibs with oculocutaneous albinism were detected on a private farm, we were interested in knowing whether their phenotype was caused by an already known gene/mutation. Results: Analysis of genotyping data (50K) of the two albino individuals, their mothers and five other relatives identified a 47.61-Mb candidate haplotype on Bos taurus chromosome BTA20. Subsequent comparisons of the sequence of this haplotype with sequence data from four Braunvieh sires and the Aurochs genome identified two possible candidate causal mutations at positions 39,829,806 bp (G/A;R45Q) and 39,864,148 bp (C/T;T444I) that were absent in 1682 animals from various bovine breeds included in the 1000 bull genomes project. Both polymorphisms represent coding variants in the SLC45A2 gene, for which the human equivalent harbors numerous variants associated with oculocutaneous albinism type 4. We demonstrate an association of R45Q and T444I with the albino phenotype by targeted genotyping. Conclusions: Although the candidate gene SLC45A2 is known to be involved in albinism in different species, to date in cattle only mutations in the TYR and MITF genes were reported to be associated with albinism or albinism-like phenotypes. Thus, our study extends the list of genes that are associated with bovine albinism. However, further research and more samples from related animals are needed to elucidate if only one of these two single nucleotide polymorphisms or the combination of both is the actual causal variant

Elevated haplotypes frequencies reveal similarities for selection signatures in Western and Russian Simmental populations

This paper shows a straightforward, but surprisingly effective approach to detect genomic regions of importance, illustrated on two Simmental cattle populations. Medium density genomic data of 42 German/Austrian (denoted as “Western“) and 38 Russian Simmental cattle were used to identify the most frequent haplotypes within the two populations. The haplotypes were defined as non-overlapping segments of ten single nucleotide ploymorphisms (SNP). The phasing was done with the SHAPEIT software, with a follow up analysis of haplotypes using the GHap package. Despite the low sample size a number of high frequency haplotypes could be identified across the whole genome. The identified genes residing directly in these high frequency haplotypes were extremely relevant for the dual purpose Simmental cattle. A large part of these genes influenced growth rate and carcass traits, others were relevant for the milk production. A smaller proportion was connected to the reproduction, immune system and cellular processes, with indirect influence on production traits