Angle-closure glaucoma (ACG) is a subset of glaucoma affecting 16 million people1–3. Although 4 million people are bilaterally blind from ACG4,5, the causative molecular mechanisms of ACG remain to be defined. High intraocular pressure induces glaucoma in ACG. High intraocular pressure traditionally was suggested to result from the iris blocking or closing the angle of the eye, thereby limiting aqueous humor drainage. Eyes from individuals with ACG often have a modestly decreased axial length, shallow anterior chamber and relatively large lens, features that predispose to angle closure6. Here, we show that genetic alteration of a previously unidentified serine protease alters axial length and causes a mouse phenotype resembling ACG. Mutations affecting this protease also cause a severe decrease of axial length in individuals with posterior microphthalmia. Together, these data suggest that alterations of this serine protease may contribute to a spectrum of human ocular conditions including reduced ocular size and ACG.

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Many proteins necessary for sound transduction have been discovered through positional cloning of genes that cause deafness1–3. In this study, we report that mutations of LRTOMT are associated with profound non-syndromic hearing loss at the DFNB63 locus on human chromosome 11q13.3-q13.4. LRTOMT has two alternative reading frames and encodes two different proteins, LRTOMT1 and LRTOMT2, that are detected by Western blot analyses. LRTOMT2 is a putative methyltransferase. During evolution, novel transcripts can arise through partial or complete coalescence of genes4. We provide evidence that in the primate lineage LRTOMT evolved from the fusion of two neighboring ancestral genes, which exist as separate genes (Lrrc51and Tomt) in rodents.

Seroepidemiological studies have indicated that Helicobacter pylori infection might be a possible risk factor for colorectal adenocarcinoma (CRC) development. However, limited information is available as to whether or not Helicobacter species are present in CRC tissues. In this study the presence of Helicobacter DNA in 77 CRC biopsies was investigated by means of a Helicobacter species-specific 16S rDNA PCR assay and real-time DNA pyrosequencing of the 16S rDNA variable V3 region. Pyrosequencing revealed the presence of Helicobacter DNA sequences in 21 of 77 biopsy specimens (27 %). 16S rDNA sequences corresponding to H. pylori 26695 and H. pylori J99 were most commonly found. Intriguingly, one sequence belonged to Helicobacter mustelae, previously identified in ferrets. No significant correlations were found in the prevalence of Helicobacter DNA between colon and rectum tumour biopsies (P ¼ 0 . 815), nor between Dukes' classes A/B and C/D (P ¼ 0 . 262). 16S rDNA PCR amplification combined with pyrosequencing analysis of 16S rDNA variable V3 regions provides a powerful molecular tool to identify Helicobacter species in human biopsy specimens. INTRODUCTIONHelicobacter pylori is a microaerophilic Gram-negative spiral-shaped bacterium (Marshall & Warren, 1983) associated with chronic gastritis, peptic ulcer and gastric adenocarcinoma development (Parsonnet et al., 1991;Cover & Blaser, 1992;Logan, 1994). It has been shown that there is a significant geographical relationship between gastric cancer mortality rates and prevalence of H. pylori infection. Subtypes of H. pylori might differ in pathogenicity (Xiang et al., 1995), and a number of studies have shown that the prevalence of H. pylori expressing the cytotoxin-associated gene A (cagA) in gastric cancer patients is much higher than in age-and gender-matched controls (Parsonnet et al., 1997; Konturek et al., 2003;Semino-Mora et al., 2003). Recent reports imply that H. pylori may be an association factor involved in colorectal cancer (CRC) development in patients infected with H. pylori strains (Meucci et al., 1997;Shmuely et al., 2001). However, it is far from clear whether H. pylori is present in CRC tissues and whether or not H. pylori plays a similar role in colorectal carcinogenesis as has been proposed for gastric cancer development.16S rDNA sequence analysis has demonstrated considerable genomic diversity among H. pylori clinical isolates, and numerous sequence-specific PCR assays, combined with 16S rDNA sequencing, have been developed to identify Helicobacter species (Thoreson et al., 1995;Blom et al., 2002). We recently described a method for the rapid simultaneous molecular identification and subtyping of H. pylori by pyrosequencing analysis of the 16S rDNA variable V1 and V3 regions (Monstein et al., 2001).In this report we describe the molecular identification of Helicobacter DNA in CRC biopsies by means of a 16S rDNA PCR amplification assay combined with pyrosequencing analysis. METHODSTissue collection and DNA isolation. A total of 77 patients (45 w...