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To characterize the phenotype observed in a case series with macular disease and determine the cause.Multicenter case series.Six families (7 patients) with sporadic or multiplex macular disease with onset at 20 to 78 years, and 1 patient with age-related macular degeneration.Patients underwent ophthalmic examination; exome, genome, or targeted sequencing; and/or polymerase chain reaction (PCR) amplification of the breakpoint, followed by cloning and Sanger sequencing or direct Sanger sequencing.Clinical phenotypes, genomic findings, and a hypothesis explaining the mechanism underlying disease in these patients.All 8 cases carried the same deletion encompassing the genes TPRX1, CRX, and SULT2A1, which was absent from 382 control individuals screened by breakpoint PCR and 13 096 Clinical Genetics patients with a range of other inherited conditions screened by array comparative genomic hybridization. Microsatellite genotypes showed that these 7 families are not closely related, but genotypes immediately adjacent to the deletion breakpoints suggest they may share a distant common ancestor.Previous studies had found that carriers for a single defective CRX allele that was predicted to produce no functional CRX protein had a normal ocular phenotype. Here, we show that CRX whole-gene deletion in fact does cause a dominant late-onset macular disease.

The major determinant of prion disease incubation time in mice is thought to be the amino acid sequence of the prion protein. Two alleles of the mouse prion gene ( Prnp) have been described, where Prnp(a) (Leu-108, Thr-189) and Prnp(b) (Phe-108, Val-189) are associated with short and long incubation times, to defined prion strains, respectively. As part of a survey of inbred mouse lines, the prion gene open reading frame was sequenced and revealed a new allele, Prnp(c) (Phe-108, Thr-189), in the strain MAI/Pas. To study the influence of Prnp(c) independently of the MAI/Pas genetic background, we generated a congenic line in which Prnp(c) was bred onto the C57BL/6JOlaHsd background. Following intracerebral inoculation with Chandler/RML scrapie prions, the congenic mice showed an increased mean incubation time relative to C57BL/6JOlaHsd, of over 100 days. However, no differences were observed in the intensity and pattern of PrP immunoreactivity deposition or spongiosis. We conclude that the new allele, Prnp(c), modulates incubation time but not neuropathology and that the previous classification of mice into two distinct groups based on incubation time and Prnp genotype should now be revised.

Results from a numerical model of the Southern Ocean (the U.K. Fine-Resolution Antarctic Model) have been used to repeat the calculations of De Szoeke and Levine, who used hydrographic data to estimate the advective heat transport across a circumpolar path of constant vertically averaged temperature. The results from the model suggest that the mean flow is responsible for only a small proportion of the heat transport and that the main process carrying heat poleward across such a path is indeed eddy heat transport. A comparison is made with the heat transport across constant latitude circles. Although the mean flow (consisting of large-scale meanderings of the Antarctic Circumpolar Current across the latitude circle) plays a more important role in this case, there is good correspondence between total heat transports across contours of constant vertically averaged temperature and those across constant latitude circles. Diffusive fluxes, in part representing subgrid-scale processes, also play an imp...

A fine resolution numerical model of the Southern Ocean (the Fine Resolution Antarctic Model (FRAM)) has been used to investigate the way in which heat is supplied to the South Atlantic. The heat budget in the model is compared with other estimates and is found to be broadly realistic. The temperature structure in the Atlantic, and therefore the meridional heat transport, depend heavily on the input of heat from the Indian Ocean via the Agulhas Retroflection region. FRAM is compared with three models which do not exhibit a significant input of heat from the Indian Ocean. These models also have a lower equatorward heat transport in the South Atlantic. Horizontal resolution affects the amount of Agulhas transfer with coarser resolution leading to lower heat transport in the Atlantic, a result which has implications for ocean models used in climate simulations.