Several dominant mutations of the mouse agouti coat colour gene have pleiotropic effects that include obesity and a yellow coat. The Ay allele is caused by a large deletion that affects the expression of several contiguous genes. We show that three other obesity-associated agouti mutations, Aiy, Asy and Avy, are due to different molecular alterations that result in ubiquitous expression of a chimaeric RNA that encodes a normal agouti protein. The Aiy and Avy alleles are caused by insertion of an intracisternal A particle element 1 kb or 100 kb, respectively, upstream of agouti coding sequences. These results provide a model for other genes that show allele-specific imprinting, and demonstrate that molecular mechanisms typically responsible for activation of proto-oncogenes can also lead to other disease phenotypes.
The agouti coat color gene encodes a p e sing molecule that controls the production of yellow and black pigment by meanoytes hin hair follicles. Some agouti alleles affect the dorsum and ventrum independently, which has provided the basis for sp tion that agouti gene action in different regions of the body is controlled by distinct genetic lci that are closely linked. Using a combination ofcDNA cloning and RNA expression studies, we find that alternative isoforms of agouti mRNA contain different noncoding firstexons located 100 kb apart, whose patterns of expression indicate independent control by regulatory elements that are either ventral specific or hair cycle specific. These results demonstrate that the apparent genetic complexity of the agouti locus is explained by the existence of multiple regulatory elements exerting control over a single coding sequence and provide a conceptual basis for understanding differences in dorsal and ventral hair coloration in many mammal species. The ventral-specific agouti isoform represents an example of a transcript whose expression is restricted to ventral skin and provides an approach to investigate the mechanisms by which dorsal-ventral differences in gene expression are established and maintained.
The intentional translocation of animals is an important tool for species conservation and ecosystem restoration, but reported success rates are low, particularly for threatened and endangered species. Publication bias further distorts success rates because the results of successful translocations may be more likely to be published than failed translocations. We conducted the first comprehensive review of all published and unpublished translocations of herpetofauna in New Zealand to assess publication bias. Of 74 translocations of 29 species in 25 years, 35 have been reported in the published literature, and the outcomes of 12 have been published. Using a traditional definition of success, publication bias resulted in a gross overestimate of translocation success rates (41.7% and 8.1% for published and all translocations, respectively), but bias against failed translocations was minimal (8.3% and 6.8%, respectively). Publication bias against translocations with uncertain outcomes, the vast majority of projects, was also strong (50.0% and 85.1% for published and all translocations, respectively). Recent translocations were less likely to be published than older translocations. The reasons behind translocations were related to publication. A greater percentage of translocations for conservation and research were published (63.3% and 40.0%, respectively) than translocations for mitigation during land development (10.0%). Translocations conducted in collaboration with a university were more frequently published (82.7% and 24.4%, respectively). To account for some of this publication bias, we reassessed the outcome of each translocation using a standardized definition of success, which takes into consideration the species' life history and the time since release. Our standardized definition of translocation success provided a more accurate summary of success rates and allows for a more rigorous evaluation of the causes of translocation success and failure in large-scale reviews.
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