Bone morphogenetic protein 15 (BMP15) is a member of the transforming growth factor beta superfamily, is specifically expressed in oocytes and is essential for sheep prolificacy. Reported mutations in this gene cause increased ovulation rate and infertility in a dosage-sensitive manner. In this work, a new naturally occurring mutation in the BMP15 gene from the ovine Rasa Aragonesa breed is des...

Adenomatous polyposis coli (APC) inactivating mutations are present in most human colorectal cancers and some other cancers. The APC protein regulates the β-catenin protein pool that functions as a co-activator of T cell factor (TCF)-regulated transcription in Wnt pathway signaling. We studied effects of reduced dosage of the Ctnnb1 gene encoding β-catenin in Apc-mutation-induced colon and ovar...

Saccharomyces cerevisiae glutaminyl-tRNA synthetase mutants were isolated through systematic screening of tight Glnderivatives of a leaky glutamine auxotroph. These mutations define a single nuclear gene, GLN4. The gln4-1 mutation is specific for Gln-tRNA synthetase and shows a dosage effect in heterozygous diploids. The wild-type Gln-tRNA synthetase exhibits a Km for glutamine of 25 ,uM; the g...

A family history of Parkinson's disease (PD) is the most commonly reported risk factor after age, suggesting a genetic component to the disease in a sub-group of patients. Mutations in at least six genes have been identified that can lead to monogenic forms of PD. We screened a sample of 74 early-onset PD cases out of a cohort of 950 patients (onset <50 years) for genetic abnormalities in known...

Drug-resistant mutants of somatic cell lines fall into two classes: one seems to correspond to classical gene mutation, the other is characterized, albeit transiently, by karyotypic instability, high reversion frequency, and low plating efficiency. An interpretation of the origin of these drug-resistant mutants is offered on the basis of chromosomal variation, which generates variation of the n...

CONTEXT Heterozygous inactivating PAX8 mutations cause congenital hypothyroidism. Although more than 30 mutation carriers have been reported, no histological examination of the thyroid has been conducted. OBJECTIVE The objective of this study was to document the histological characteristics of the thyroid tissue harboring a PAX8 mutation. SUBJECTS AND METHODS The patient was a 40-yr-old fem...

high-dose extended-interval dosage (hded) regimen of aminoglycosides is now considered as the standard dosage strategy in sepsis. although safety and efficacy of this dosing regimen is well studied, but new experiments show increased the risk of resistance development associated with %t>mic less than 60% of the dosing interval following extended interval dosing. moreover, limited information is...

About 30% of protein-coding genes in the human genome are related through two whole genome duplication (WGD) events. Although WGD is often credited with great evolutionary importance, the processes governing the retention of these genes and their biological significance remain unclear. One increasingly popular hypothesis is that dosage balance constraints are a major determinant of duplicate ge...

In Drosophila, dosage compensation augments X chromosome-linked transcription in males relative to females. This process is achieved by the Dosage Compensation Complex (DCC), which associates specifically with the male X chromosome. We previously found that the morphology of this chromosome is sensitive to the amounts of the heterochromatin-associated protein SU(VAR)3-7. In this study, we exami...