Comparative analyses of multi-species sequences from targeted genomic regions

The systematic comparison of genomic sequences from different organisms represents a central focus of contemporary genome analysis. Comparative analyses of vertebrate sequences can identify coding and conserved non-coding regions, including regulatory elements, and provide insight into the forces that have rendered modern-day genomes. As a complement to whole-genome sequencing efforts, we are sequencing and comparing targeted genomic regions in multiple, evolutionarily diverse vertebrates. Here we report the generation and analysis of over 12 megabases (Mb) of sequence from 12 species, all derived from the genomic region orthologous to a segment of about 1.8 Mb on human chromosome 7 containing ten genes, including the gene mutated in cystic fibrosis. These sequences show conservation reflecting both functional constraints and the neutral mutational events that shaped this genomic region. In particular, we identify substantial numbers of conserved non-coding segments beyond those previously identified experimentally, most of which are not detectable by pair-wise sequence comparisons alone. Analysis of transposable element insertions highlights the variation in genome dynamics among these species and confirms the placement of rodents as a sister group to the primates.     

Mutations in TMPRSS6 cause iron-refractory iron deficiency anemia (IRIDA)

Iron deficiency is usually attributed to chronic blood loss or inadequate dietary intake. Here, we show that iron deficiency anemia refractory to oral iron therapy can be caused by germline mutations in TMPRSS6, which encodes a type II transmembrane serine protease produced by the liver that regulates the expression of the systemic iron regulatory hormone hepcidin. These findings demonstrate that TMPRSS6 is essential for normal systemic iron homeostasis in humans.     

In situ Os isotopes in abyssal peridotites bridge the isotopic gap between MORBs and their source mantle

Abyssal peridotites are assumed to represent the mantle residue of mid-ocean-ridge basalts (MORBs). However, the osmium isotopic compositions of abyssal peridotites and MORB do not appear to be in equilibrium, raising questions about the cogenetic relationship between those two reservoirs. However, the cause of this isotopic mismatch is mainly due to a drastic filtering of the data based on the possibility of osmium contamination by sea water. Here we present a detailed study of magmatic sulphides (the main carrier of osmium) in abyssal peridotites and show that the 187Os/188Os ratio of these sulphides is of primary mantle origin and can reach radiogenic values suggesting equilibrium with MORB. Thus, the effect of sea water on the osmium systematics of abyssal peridotites has been overestimated and consequently there is no true osmium isotopic gap between MORBs and abyssal peridotites.