α-thalassaemia

Alpha-thalassaemia is inherited as an autosomal recessive disorder characterised by a microcytic hypochromic anaemia, and a clinical phenotype varying from almost asymptomatic to a lethal haemolytic anaemia

A large deletion in the human alpha-globin cluster caused by a replication error is associated with an unexpectedly mild phenotype.

We have characterized a newly identified 16.6 kb deletion which removes a significant proportion of the human alpha-globin cluster including the psizeta1, alpha(D), psialpha1 and alpha2-globin genes but leaves the duplicated alpha1 gene intact. This complicated rearrangement results from a combination of slippage and strand switching at sites of microhomology during replication. Functional analysis shows that expression of the remaining alpha1 gene is increased, rather than down-regulated by this deletion. This could be related to its proximity to the remote upstream alpha-globin regulatory elements or reduced competition for these elements in the absence of the dominant alpha2-globin gene. The finding of a very mild phenotype associated with such an extensive deletion in the alpha-globin cluster implies that much of the DNA removed by the deletion is likely to be functionally unimportant. These findings suggest that other than the upstream regulatory elements and promoter proximal elements there are unlikely to be additional positive cis-acting sequences in the alpha-globin cluster

The Yungul carbonatite dykes associated with the epithermal fluorite deposit at Speewah, Kimberley, Australia: carbon and oxygen isotope constraints on their origin

The Yungul carbonatite dykes at Speewah in the Kimberley region of Western Australia were emplaced along a north-trending splay from the northeast-trending Greenvale Fault located at the western boundary of the Halls Creek Orogen. The Yungul carbonatite dykes intrude a thick composite sill of the Palaeoproterozoic Hart Dolerite (~1,790 Ma), consisting of tholeiitic dolerite and gabbro with its felsic differentiates that form the Yilingbun granophyres and associated granites. The carbonatite dykes consist of massive, calcite carbonatite that host very coarse, pegmatitic veins and pods of calcite, and have largely replaced (carbonatitized) and fenitized the country rock Hart Dolerite suite in a zone up to 150 m wide. Dykes of red-brown siliceous fluidized-breccia and epithermal-textured veins consisting of bladed quartz, adularia and fluorite are closely associated with the carbonatite dykes. The Yungul carbonatites are closely associated with fluorite occurrences with resources currently reported as 6.7 Mt at 24.6% CaF2. The precise age of the Yungul carbonatite is not known, although it is believed to be post early Cambrian. The total REE content of the Yungul carbonatite is low (174.0–492.8 ppm; La/Yb 2.28–10.74) and thus atypical for calciocarbonatite. Chondrite-normalized REE patterns for the carbonatite are relatively flat compared to average calciocarbonatite, and show small negative Eu anomalies. These unusual geochemical features may have been acquired from the Hart Dolerite suite during emplacement of the carbonatite, a process that involved extensive replacement and fenitization of country rocks. Carbon and oxygen isotope compositions of massive calcite carbonatite and the coarse calcite veins and pods from the carbonatite suggest a deep-seated origin. The C and O isotope compositions show an overall positive correlation that can be attributed to both magmatic and magmatic-hydrothermal processes in their evolution. The magmatic δ13C-δ18O trend is also indicative of crustal contamination and/or low-temperature water/rock exchange. The carbon isotopic compositions have δ13C values that range from about −5.2‰ to −6.3‰ that support a mantle-derived origin for the Yungul carbonatites and are consistent with earlier conclusions based on whole-rock geochemistry and radiogenic isotopes studies