The Newfoundland and Labrador mosaic founder population descends from an Irish and British diaspora from 300 years ago.

The founder population of Newfoundland and Labrador (NL) is a unique genetic resource, in part due to its geographic and cultural isolation, where historical records describe a migration of European settlers, primarily from Ireland and England, to NL in the 18th and 19th centuries. Whilst its historical isolation, and increased prevalence of certain monogenic disorders are well appreciated, details of the fine-scale genetic structure and ancestry of the population are lacking. Understanding the genetic origins and background of functional, disease causing, genetic variants would aid genetic mapping efforts in the Province. Here, we leverage dense genome-wide SNP data on 1,807 NL individuals to reveal fine-scale genetic structure in NL that is clustered around coastal communities and correlated with Christian denomination. We show that the majority of NL European ancestry can be traced back to the south-east and south-west of Ireland and England, respectively. We date a substantial population size bottleneck approximately 10-15 generations ago in NL, associated with increased haplotype sharing and autozygosity. Our results reveal insights into the population history of NL and demonstrate evidence of a population conducive to further genetic studies and biomarker discovery.

Gene transfer and in vivo promoter analysis of the rat progesterone receptor using a herpes simplex virus viral vector.

The progesterone receptor (PR) gene is expressed in cells of the anterior pituitary and hypothalamus, and PR levels are regulated by estrogen (E) in a tissue-specific fashion. To demonstrate that E induces transcription via the PR promoter, and to identify sequences within the PR promoter responsible for tissue-specific and hormonal regulation, we have utilized a defective herpes simplex virus vector for direct gene transfer into the rat pituitary and brain. We designed a viral amplicon expressing the beta-galactosidase gene under the regulation of a 2.1-kb PR promoter fragment to create a defective viral vector for gene transfer into the brain. Following injection of this vector into the pituitary and brain, its pattern of expression and ability to respond to estradiol 3-benzoate (EB) were examined. In the pituitary, lacZ activity was observed in cells of the anterior lobe (AL). However, no activity was seen in the neurointermediate lobe (NIL), demonstrating tissue specific transcriptional regulation. A approximately sixfold increase in cells demonstrating beta-galactosidase activity was observed in the AL following treatment with EB. Likewise, injection of defective viral vector into the hypothalamus followed by treatment with EB resulted in a approximately eightfold increase in cells demonstrating beta-galactosidase activity including the very cell groups responsible for EB-dependent reproductive behavior. In contrast, no vector dependent activity was observed in the caudate nucleus, a tissue with no endogenous expression of PR, despite polymerase chain reaction evidence demonstrating the presence of the vector in this tissue. These results demonstrate that the 2.1-kb PR promoter fragment contains the sequence information required for correct tissue and hormonal regulation of PR.