The srfA locus of BaciUlus subtilis is defined by a transposon Tn917 insertion and is required for productpon of the peptide secondary metabolite surfactin. The srfA locus was isolated by cloning the DNA flanking srfA::Tn917 insertions followed by chromosome walking. The cloned region is an operon of oyer 25 kb which covers the transcription initiation region but not the intact 3' end of srfA. csh-293, which was previously identified as a Tn9171ac mutation that impairs competence development and causes a condifoWl defect in sporulation, was known to be located in the vicinity of the srfA locus within the B. subtlis genome. The csh-293::Tn9171ac mutation was discovered to cause a defect in surfactin production and was shown to be located in the srfA operon by its cotransformation with srfA mutations and' by Southern hybridization analysis. Insertion mutations in srfA, created by the chromosomal integration of plasmids bearing overlapping srfA DNA fragments, were ex for their effects on surfactin production, competence, and sporulation. AB three processes were found to require the intact 5' half of the srfA operon, whereas the 3' half of srfA was found to be required for sporulation and surfactin production but not competence. These experiments show that srfA gene products function in B. subtilis cell specialization and differentiation.

We conducted genome-wide association studies of non-Hodgkin lymphoma using Illumina HumanHap550 BeadChips to identify subtype-specific associations in follicular, diffuse large B-cell and chronic lymphocytic leukemia/small lymphocytic lymphomas. We found that rs6457327 on 6p21.33 was associated with susceptibility to follicular lymphoma (FL, N=189 cases/592 controls) with validation in an additional 456 FL cases and 2,785 controls (combined allelic pvalue=4.7×10 −11 ). The region of strongest association overlaps C6orf15(STG), located near psoriasis susceptibility region 1(PSORS1).Non-Hodgkin lymphoma (NHL) is a heterogeneous group of neoplasms of B-and T-cells that vary in their causes and molecular profiles 1 . With the fifth highest incidence amongst all cancers in the U.S., the annual incidence of NHL has doubled since the 1970s. With the increasing evidence supporting the importance of genetic determinants in lymphomagenesis 2 , there is a strong impetus to identify genetic risk factors. Epidemiological and biological evidence suggest that environmental and genetic risk factors differ for the common NHL subtypes, follicular (FL), diffuse large B-cell (DLBCL) and chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) 1 . We therefore conducted genome-wide association studies (GWAS) using separate DNA pools from 189 FL, 221 9Correspondance to: Dr. Christine Skibola, School of Public Health, 237A Hildebrand Hall, University of California, Berkeley, California 94720-7356, 510) 643-5041 tel/(510) 642-0427 fax/ chrisfs@berkeley.edu. Author Contributions CFS, JS, AB-W, EAH and NB are principal investigators for the participating studies; LA and JR did DNA extraction, normalization and quality control; KB and KI prepared DNA pools and performed the genome scan and analysis; DC, CFS, KB, MTS and LZ consulted on study design; LA undertook genotyping; JC performed expression analysis; DC, PMB, AN and LC performed the statistical analyses; LC and EH conducted bioinformatics analyses; CSF, LC and KB wrote the manuscript. Fig. 1; for description of study populations see Supplementary Table 1). We restricted genotyping to DNA collected from individuals with European ancestry as determined by AIMS genotyping 4 to diminish potential underlying population stratification. Self-reported ethnicity and ancestry data were highly correlated (95%) and used to construct homogeneous DNA pools of participants of European descent. NIH Public AccessIn the first phase, pools were hybridized to Human Hap550v.3 BeadChips (Illumina, San Diego, CA), and SNPs were ranked after adjusting for pooling error 5 . The top 30 ranked SNPs for each NHL subtype were subsequently individually genotyped across the NC1 sample set to confirm the accuracy of estimated allele frequency differences from the pooled data. 87% of raw allelic p-values were <0.05 (Supplementary Tables2a-c), and genotype frequencies did not significantly differ from Hardy-Weinberg equilibrium. 32 SNPs with subtype-specific allelic q-values (corrected p) <0.05 ...

Genetic susceptibility studies of lymphoma may serve to identify at risk populations and clarify important disease mechanisms. This review considered all studies published through October 2006 on the contribution of genetic polymorphisms in the risk of lymphoma. Numerous studies implicate the role of genetic variants that promote B-cell survival and growth with increased risk of lymphoma. Several reports including a large pooled study by InterLymph, an international consortium of non-Hodgkin lymphoma (NHL) case-control studies, found positive associations between variant alleles in TNF -308G>A and IL10 -3575T>A genes and risk of diffuse large B-cell lymphoma. Four studies reported positive associations between a GSTT1 deletion and risk of Hodgkin and non-Hodgkin lymphoma. Genetic studies of folate-metabolizing genes implicate folate in NHL risk, but further studies that include folate and alcohol intakes are needed. Links between NHL and genes involved in energy regulation and hormone production and metabolism may provide insights into novel mechanisms implicating neuro-and endocrine-immune cross-talk with lymphomagenesis. However, this links will need replication in larger populations. Numerous studies suggest that common genetic variants with low penetrance influence lymphoma risk, though replication studies will be needed to eliminate false positive associations.