Genomic imprinting has been implicated in the onset of several embryonal tumours but the mechanism is not well understood. Maternal chromosome 11p15 loss of heterozygosity and paternal chromosome 11 isodisomy suggest that imprinted genes are involved in the onset of Wilms' tumour and the Beckwith-Wiedemann syndrome. The insulin-like growth factor II (IGF2) gene located at 11p15.5 has been put forward as a candidate gene as it is maternally imprinted (paternally expressed) in the mouse, and is expressed at high levels in Wilms' tumours. We report here that the IGF2 gene is expressed from the paternal allele in human fetal tissue, but that in Wilms' tumour expression can occur biallelically. These results provide, to our knowledge, the first evidence that relaxation of imprinting may play a role in the onset of disease and suggest a new genetic mechanism involved in the development of cancer.

Chromosomal diversity and relationships among 126 Streptococcus pyogenes strains expressing M1 protein from 13 countries on five continents were analyzed by multilocus enzyme electrophoresis and restriction fragment profiling by pulsed-field gel electrophoresis. All isolates were studied for the presence of the gene encoding streptococcal pyrogenic exotoxin A by PCR. Strain subsets were also examined by automated DNA sequencing for allelic polymorphism in genes encoding M protein (emm), streptococcal pyrogenic exotoxin A (speA), streptokinase (ska), pyrogenic exotoxin B (interleukin-1␤ convertase) (speB), and C5a peptidase (scp). Seven distinct emm1 alleles that encode M proteins differing at one or more amino acids in the N-terminal variable region were identified. Although substantial levels of genetic diversity exist among M1-expressing organisms, most invasive disease episodes are caused by two subclones marked by distinctive multilocus enzyme electrophoretic profiles and pulsed-field gel electrophoresis restriction fragment length polymorphism (RFLP) types. One of these subclones (ET 1/RFLP pattern 1a) has the speA gene and was recovered worldwide. Identity of speA, emm1, speB, and ska alleles in virtually all isolates of ET 1/RFLP type 1a means that these organisms share a common ancestor and that global dispersion of this M1-expressing subclone has occurred very recently. The occurrence of the same emm and ska alleles in strains that are well differentiated in overall chromosomal character demonstrates that horizontal transfer and recombination play a fundamental role in diversifying natural populations of S. pyogenes.

The increasing use of culture independent diagnostic testing for the diagnosis of Neisseria gonorrhoeae infection has led to gaps in surveillance of antimicrobial resistance (AMR) rates due to limited availability of cultures. Our study reports the findings of a second national survey of N. gonorrhoeae in New Zealand, utilizing whole-genome sequencing (WGS) to study the population structure, prevalence of AMR, epidemiology and transmission of gonorrhoea isolates. We analysed 314 isolates and found a strong correlation between carriage of acquired resistance genes or chromosomal point mutations and phenotypic susceptibility testing results. Overall, the New Zealand rates of azithromycin resistance and decreased susceptibility to ceftriaxone remain lower than in most countries, which are part of the World Health Organization (WHO) Global Gonococcal Antimicrobial Surveillance Programme (GASP). The phylogeny provides evidence of a diverse population significantly associated with sexual behaviour groups. Transmission clustering with a ten single nucleotide polymorphism (SNP) cut-off identified 49 clusters, of which ten were solely associated with men who have sex with men (MSM), whereas remaining clusters included heterosexual patients, as well as MSM, suggesting that bridging of sexual networks is occurring. Utilizing pairwise SNP differences between isolates of the same sequence types we determined genetic variation for the three typing schemes used in this study [Multi locus sequence typing (MLST), multi-antigen sequence typing (NG-MAST), and sequence typing for antimicrobial resistance (NG-STAR)]. A median of 0.0 to 52.5 pairwise SNP differences within a single NG-STAR sequence type underlines previous findings of the superiority of the NG-STAR typing scheme in terms of genomic inherency. With our analysis incorporating epidemiological and genomic data, we were able to show a comprehensive overview of the N. gonorrhoeae population circulating in New Zealand, focussing on AMR and transmission within sexual networks. Regular surveillance studies to understand the origin, evolution and spread of AMR for gonorrhoea remain necessary to make informed decisions about public health guidelines, as the internationally rising rates of ceftriaxone and azithromycin resistance have already led to adaptation of current treatment guidelines in the UK and the USA, highlighting the importance of regular surveillance in individual countries.

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