Adam D. Booth

Null mutations in LTBP2 cause primary congenital glaucoma

Primary congenital glaucoma (PCG) is an autosomal-recessive condition characterized by high intraocular pressure (IOP), usually within the first year of life, which potentially could lead to optic nerve damage, globe enlargement, and permanent loss of vision. To date, PCG has been linked to three loci: 2p21 (GLC3A), for which the responsible gene is CYP1B1, and 1p36 (GLC3B) and 14q24 (GLC3C), for which the genes remain to be identified. Here we report that null mutations in LTBP2 cause PCG in four consanguineous families from Pakistan and in patients of Gypsy ethnicity. LTBP2 maps to chromosome 14q24.3 but is around 1.3 Mb proximal to the documented GLC3C locus. Therefore, it remains to be determined whether LTBP2 is the GLC3C gene or whether a second adjacent gene is also implicated in PCG. LTBP2 is the largest member of the latent transforming growth factor (TGF)-beta binding protein family, which are extracellular matrix proteins with multidomain structure. It has homology to fibrillins and may have roles in cell adhesion and as a structural component of microfibrils. We confirmed localization of LTBP2 in the anterior segment of the eye, at the ciliary body, and particularly the ciliary process. These findings reveal that LTBP2 is essential for normal development of the anterior chamber of the eye, where it may have a structural role in maintaining ciliary muscle tone.

Water-Content of Glacier-Ice: Limitations on Estimates from Velocity Analysis of Surface Ground-Penetrating Radar Surveys

The rheology of ice is strongly controlled by its liquid water content. Since water content and its distribution also exert a strong control on radar propagation velocity and attenuation, this provides a potential remote technique for assessing ice-water content. A suite of surface ground-penetrating radar (GPR) surveys have been undertaken on two glaciers, Tsanfleuron Glacier in the European Alps and Bakaninbreen, Svalbard in order to determine their water content variation with depth. Common-offset surface radar profiling shows both glaciers have a two-layered structure, with a shallow layer characterised by low returned radar power and a deeper layer characterised by strong scattering. The thickness of these layers varies rapidly across the glaciers. In order to provide a robust interpretation of the properties of the layers within these glaciers we present a quantitative semblance analysis of two common midpoint surveys, making estimates of layer thickness and water content. This analysis includes a M...

Seismic evidence of mechanically weak sediments underlying Russell Glacier, West Greenland

Abstract Amplitude-versus-angle (AVA) analysis of a seismic reflection line, imaged 13 km from Russell Glacier terminus, near the western margin of the Greenland ice sheet (GrIS), suggests the presence of sediment at the bed. The analysis was complicated by the lack of identifiable multiples in the data due to a highly irregular and crevassed ice surface, rendering deeper seismic returns noisy. A modified technique for AVA processing of glacial seismic data using forward modelling with primary reflection amplitudes and simulated multiple amplitudes is presented here. Our analysis demonstrates that AVA analysis can be applied to areas with noisy seismic returns and indicates that sediment underlies the seismic study site. Our data are inconsistent with the common assumption that the GrIS is underlain only by hard bedrock, but consistent with the presence of subglacial sediment with porosity between 30% and 40%. As analysis and modelling of ice-sheet dynamics requires a sound knowledge of the underlying basal materials, subglacial sediment should be taken into account when considering ice dynamics in this region of the GrIS.

Streaming flow of an Antarctic Peninsula palaeo-ice stream, both by basal sliding and deformation of substrate

Acoustic sub-bottom profiler surveys on the northeast Antarctic Peninsula shelf indicate that parts of the seabed are underlain by an acoustically transparent layer that is thin on the inner shelf and becomes thicker and more extensive towards the outer shelf. Sedimentological and geophysical data are combined to construct a bed model where streaming ice flow, by both deformation and basal sliding, took place within cross-shelf troughs. The model suggests only limited deformation contributed to fast flow on the inner shelf, i.e. in the onset zone of ice streaming, where the bed was predominantly underlain by a stiff till. Thus, fast ice flow in this area might have been by basal sliding, with deformation confined to discontinuous patches of soft till <40 cm thick. Towards the middle and outer shelf, extensive, thick sequences of soft till suggest a change in the dominant subglacial process towards widespread deformation. This downstream change from basal sliding to subglacial deformation is manifest in the transition from stiff-till dominance to soft-till dominance, while a downstream increase in ice flow velocity is evident from the complex geomorphic imprint on the inner shelf evolving to the more restricted set of bedforms on the outer shelf.

Semblance response to a ground-penetrating radar wavelet and resulting errors in velocity analysis

The propagation velocity of a ground-penetrating radar (GPR) wavelet may be used to derive physical subsurface properties, including layer thickness, porosity and water content. We describe a systematic error in semblance analysis of GPR common-midpoint (CMP) data, arising from the response of the statistic to the waveform of the GPR pulse. Only the first-breaks of GPR wavelets express true velocities and traveltimes but these cannot deliver a semblance response since they have zero amplitude; instead, this response derives from subsequent wavelet half-cycles, delayed from the first-break. This delay causes semblance picks to express slower velocity and later traveltime with respect to true quantities, even for simple cases of reflectivity. For a two-layer synthetic CMP data set, in which the GPR source pulse via a 500 MHz Berlage wavelet, semblance picks underestimate interval velocities of 0.135 m/ns and 0.060 m/ns by 10.0% and 2.0%, respectively. Velocity biases are corrected using the coherence statistic to simulate first-break traveltimes from a set of velocity picks, in a process termed ‘backshifting’. A t2–x2 linear regression of simulated first-breaks yields smaller errors in the same interval velocities of –2.2% and –1.0%. A first real-data example considers a reflection from the base of a 3.39 m thick air-gap. Semblance analysis estimates the air-wave velocity as 0.289 m/ns (–3.6% error) and the air-gap thickness as 3.59 m ( 6.1% error); backshifting yields equivalent estimates of 0.302 m/ns ( 0.9% error) and 3.35 m (–1.2% error). In a second example, semblance- and backshifting-derived velocity models overestimate the thickness of clay-rich archaeological deposits by 19.0% and 3.1%, respectively. Backshifting is a simple modification to conventional practice and is recommended for any analysis where physical subsurface properties are to be derived from the output GPR velocity.

Seismic wave attenuation in the uppermost glacier ice of Storglaciären, Sweden

We conducted seismic refraction surveys in the upper ablation area of Storglaciaren, a small valley glacier located in Swedish Lapland. We estimated seismic-wave attenuation using the spectral-ratio method on the energy travelling in the uppermost ice with an average temperature of approximately −1 °C. Attenuation values were derived between 100 and 300 Hz using the P-wave quality factor, Q P, the inverse of the internal friction. By assuming constant attenuation along the seismic line we obtained mean Q P = 6 ± 1. We also observed that Q P varies from 8 ± 1 to 5 ± 1 from the near-offset to the far-offset region of the line, respectively. Since the wave propagates deeper at far offsets, this variation is interpreted by considering the temperature profile of the study area; far-offset arrivals sampled warmer and thus more-attenuative ice. Our estimates are considerably lower than those reported for field studies in polar ice (∼500–1700 at −28°C and 50–160 at −10°C) and, hence, are supportive of laboratory experiments that show attenuation increases with rising ice temperature. Our results provide new in situ estimates of Q P for glacier ice and demonstrate a valuable method for future investigations in both alpine and polar ice.

Mpdz null allele in an avian model of retinal degeneration and mutations in human leber congenital amaurosis and retinitis pigmentosa

PURPOSE To identify the defective gene in the sex-linked, recessively inherited retinal dysplasia and degeneration (rdd) chicken and to search for the human equivalent disease. METHODS Microsatellites from chicken chromosome Z were genotyped in 77 progeny of a carrier male (rdd/+) and an affected female (rdd/W), and candidate genes were sequenced. Retinal cross-sections from rdd and wild-type birds were analyzed by immunohistology. The human orthologous gene was screened in a panel of archival DNAs from 276 patients with retinitis pigmentosa (RP) or Leber congenital amaurosis (LCA) using melting curve analysis and DNA sequencing. RESULTS The rdd locus was refined to an approximately 3-Mb region on chromosome Z. Sequence analysis identified a C→T change in the mpdz gene that created a premature stop codon (c.1372C→T, p.R458X), which segregated with the disease phenotype. As expected, the full-length mpdz protein was absent in rdd retinas, but in wild-type birds, it localized to the retinal outer limiting membrane, where it may have a role in the interactions between photoreceptors and Müller glia cells. The screen to identify the human equivalent disease found 10 heterozygous variants in the orthologous gene in patients with RP (three missense and two null alleles) and LCA (four missense and one null allele). CONCLUSIONS These findings reveal that MPDZ is essential for normal development of the retina and may have a role in maintaining photoreceptor integrity. The identification of human mutations suggests that MPDZ plays a role in human retinal disease, but the precise nature of this role remains to be determined.

The genetics of primary open angle glaucoma

The advent of the discipline of molecular genetics over the past decade has led to a dramatic growth in our understanding of the genetics of a myriad of diseases. Ophthalmology has benefited greatly from this new technology, with significant advances in our knowledge about conditions as varied as aniridia and retinitis pigmentosa.1 2 Our understanding of the genetics of primary open angle glaucoma (POAG) may not be as clear as with some other ophthalmic conditions but, nevertheless, there have been great advances since the last review about the genetics of glaucoma published in the BJO in 1980.3 At that time, our knowledge was based on a number of conflicting studies attempting to link human polymorphisms, such as the ability to taste phenyl thiocarbamide, with glaucoma.4 Nowadays, the positions of genes responsible for various forms of glaucoma have been localised, not just to individual chromosomes, but to specific small regions on those chromosomes. Recently, for the first time, a gene responsible for a specific form of POAG has been identified. This review aims to highlight and explain the important recent advances in our understanding of the genetics of POAG. Primary open angle glaucoma, for the purpose of this review, refers to those cases of glaucoma in which there is not only no evident antecedent or related ocular disease but also the angle of the anterior chamber remains open at all times.5 The possibility of a genetic predisposition to glaucoma was first realised in 1842 when Benedict reported the occurrence of glaucoma in two sisters.6 Despite the intervening 150 years, our understanding of the genetics of POAG remains unclear. Certainly, most POAG pedigrees do not show a simple Mendelian pattern of inheritance. However, relatives of patients with glaucoma do run an increased risk of developing the condition …

Extensive Retreat of Greenland Tidewater Glaciers, 2000–2010

Abstract Overall mass loss from the Greenland ice sheet nearly doubled during the early 2000s resulting in an increased contribution to sea-level rise, with this step-change being mainly attributed to the widespread frontal retreat and accompanying dynamic thinning of tidewater glaciers. Changes in glacier calving-front positions are easily derived from remotely sensed imagery and provide a record of dynamic change. However, ice-sheet-wide studies of calving fronts have been either spatially or temporally limited. In this study multiple calving-front positions were derived for 199 Greenland marine-terminating outlet glaciers with width greater than 1 km using Landsat imagery for the 11-year period 2000–2010 in order to identify regional seasonal and inter-annual variations. During this period, outlet glaciers were characterized by sustained and substantial retreat summing to more than 267 km, with only 11 glaciers showing overall advance. In general, the pattern of mass loss detected by GRACE (Gravity Recovery and Climate Experiment) and other measurements is reflected in the calving record of Greenland glaciers. Our results suggest several regions in the south and east of the ice sheet likely share controls on their dynamic changes, but no simple single control is apparent.

Deriving ice thickness, glacier volume and bedrock morphology of the Austre Lovénbreen (Svalbard) using Ground-penetrating Radar

The Austre Lovenbreen is a 4.6 km2 glacier on the Archipelago of Svalbard (79°N) that has been surveyed over the last 47 years in order of monitoring in particular the glacier evolution and associated hydrological phenomena in the context of nowadays global warming. A three-week field survey over April 2010 allowed for the acquisition of a dense mesh of Ground-penetrating Radar (GPR) data with an average of 14683 points per km2 (67542 points total) on the glacier surface. The profiles were acquired using a Mala equipment with 100 MHz antennas, towed slowly enough to record on average every 0.3 m, a trace long enough to sound down to 189 m of ice. One profile was repeated with 50 MHz antenna to improve electromagnetic wave propagation depth in scattering media observed in the cirques closest to the slopes. The GPR was coupled to a GPS system to position traces. Each profile has been manually edited using standard GPR data processing including migration, to pick the reflection arrival time from the ice-bedrock interface. Snow cover was evaluated through 42 snow drilling measurements regularly spaced to cover all the glacier. These data were acquired at the time of the GPR survey and subsequently spatially interpolated using ordinary kriging. Using a snow velocity of 0.22 m/ns, the snow thickness was converted to electromagnetic wave travel-times and subtracted from the picked travel-times to the ice-bedrock interface. The resulting travel-times were converted to ice thickness using a velocity of 0.17 m/ns. The velocity uncertainty is discussed from a common mid-point profile analysis. A total of 67542 georeferenced data points with GPR-derived ice thicknesses, in addition to a glacier boundary line derived from satellite images taken during summer, were interpolated over the entire glacier surface using kriging with a 10 m grid size. Some uncertainty analysis were carried on and we calculated an averaged ice thickness of 76 m and a maximum depth of 164 m with a relative error of 11.9%. The volume of the glacier is derived as 0.3487±0.041 km3. Finally a 10-m grid map of the bedrock topography was derived by subtracting the ice thicknesses from a dual-frequency GPS-derived digital elevation model of the surface. These two datasets are the first step for modelling thermal evolution of the glacier and its bedrock, as well as the main hydrological network.