2. Nature Genetics Delivering essential function
Procedures and priorities
Myles Axton - September 2005
Aim: To define the community, it’s needs
Scope: Define for NPG what we can offer as a service to community and which product to create to serve the community: if webportal, what should it contain?
Would like to discuss the individual points and communicate the results of the meeting, which should be suggestions of how to move on, to the board.
Hence input and participation important.

3. Nature Genetics founded in 1992 as sister journal to Nature NPG Research Journals Nature Biotechnology Nature Methods Nature Cell Biology Nature Medicine Nature Neuroscience Nature Structural and Molecular Biology
Thank you v much for participation and f taking the time, investing thoughts and research into this. Alan Packer sent in 8 pages, all together 13 pages

4. Landmarks 1992 p53 binding site defined
Linkage applied to complex traits
1996 Cell cycle microarray
1997 Genetics of obesity
What needs to be transmitted?
How easy could we obtain that information, please rank!

5. Nature Genetics Impact factor Seminal research papers
Definitive strategic advice
Exacting expert referees
Professional editors and production staff
Scope: What to include in the widest sense: List complete? Where can I get list from?
In the narrowest sense: Minimum?

6. Sponsored Supplements
User’s guide to the human genome II (Nov 2003)
FAQ for all users
Genetics for the Human Race (October 2004)
Genetic epidemiology with variants distributed across continental ancestry groups
Chipping Forecast III (June 2005)
Applications of microarrays to cancer
User’s guide to the mouse (November 2005)
Optimal strategy given the mouse and rat genomes, new gene trap and ES cell
resources

7. Scope Common/complex diseases Gene networks Cancer
Human disease genetics
Pharmacological genomics
Epigenetics
Developmental genetics
Functional genomics
Stem cell genetics
Genetic technology
Genome evolution

8. Technical Reports Nature Genetics Nature Biotechnology Nature Methods
Biological insights from perturbation of gene networks
by mutation, transgenic manipulation, natural variation and evolution
Nature Biotechnology
The degree of control gained over a biological system
can be as important as the basic finding
Bioinformatics
Proteomics
Systems biology
Commercial applications
Nature Methods
When the strategy rather than the biological insight is new
Molecular biology methods of interest outside genetics and genomics
Protocols

9. Career best work Nature and Nature Genetics EMBO Journal EMBO Reports
Molecular Systems Biology
Heredity

10. Get priority for your paper
Story
Is this a comprehensive and integrated set of experiments addressing
a coherent and important question? Nature Genetics referees are rarely keen
on work they see as preliminary, incremental or descriptive.
Abstract
How the experimental methods led to the conclusion
This is a qualitative conceptual advance over which work?
Why previous experiments have not addressed this point.
State of the art
For a geneticist: access to several datasets and robust statistical
procedures.
For functional studies (molecular biology or biochemistry): first, is
the basic genetics sound?
If you work with cells, do your results hold up in vivo?

11. Get priority for your paper (2)
Consult
Talk with an editor about current criteria, these evolve and are reviewed
regularly by the editorial team, but may not yet have found their way
into a recent editorial.
Referees
Recommended for particular expertise
Excluded for reasons of competition, recent collaboration or bias
Expediting
We can ensure fast review if given name and date of competing author
or journal but we will not publish any work before it meets our
standards.

12. Problem areas Biological insight is usually the issue
Clinical report on one individual
Gene identification in model organism without transferrable conclusion
Pure bioinformatics
Disease model copies human phenotype
Modification of existing technique
Descriptive gene expression profile
Human gene identification with sensitive/general phenotype
Oncogene/tumor suppressor gene identification in cell culture
Methylation correlation

13. Add value to your paper
Will your results transfer to other disciplines?
eg. medicine, anthropology, bioinformatics, bioethics.
Share research materials
NCBI, GEO, ArrayExpress, BIND, HapMap etc.
MIAME - gene expression by microarray
aCGH - genome copy number changes
Genotypes - quality of data, use to others, clinical data can be separated
Submit large datasets before review but control access

14. Association for genetic component of common disease
Criteria from:
Ioannidis et al. Nat. Genet. 29, (2001)
Meta-analysis used to recommend minimum size for association
studies and to converge on best estimate of conferred risk (odds ratio).
Lohmueller et al. Nat. Genet. 33, (2003)
25% of association studies repeated, those that repeated did so many
times. First published studies overestimate conferred risk but
publication bias not main cause. Must replicate in second
population.
Page et al. Am. J. Hum. Genet. 73, (2003)
Sherlock Holmes/ Karl Popper criteria for causation. Try to eliminate other
explanations yourself.

15. Genetic association criteria (genetics before function)
Report actual genotypes obtained and odds ratio
Replicate in a second population
Linkage disequilibrium - Analyze LD if markers are not themselves functional
variants of a candidate gene.
Multiple hypothesis testing - How was the statistical analysis corrected for
the many phenotypes and genotypes studied and the tests performed?
Stratification - Attempt to control systematic variation in genotype between
cases and controls that may result from other population genetic or
demographic factors.

16. Complex traits

17. Rice salt tolerance QTL
Ren, Gao, Li et al. September A rice quantitative trait locus for
salt tolerance encodes a sodium transporter
Mapped QTL by crossing salt tolerant O.s.indica Nona Bokra with salt sensitive O.s. japonica Koshihikari
Complementation by cDNA transgenesis
In Xenopus oocytes, KSKC1 product has lower Na+ transport activity than NSKC1
QTL affects accumulation of K+ as well as Na+ in whole plant
Resembles a loss of function salt-sensitive allele of Arabidopsis AtHKT1

18. Genomics

19. Schistosome cDNAs Hu et al. October 2003
Assigned 43,707 Schistosoma japonicum ESTs to 13,131 gene clusters
Discovered mammalian-like receptors for hormones, cytokines and neuropeptides
Significant resource for molecular parasitology researchers
Statistical analysis.
We did statistical analysis of expression profiles using tools available at
(ref. 46).
URLs.
More details of the results and the raw data are freely available for download from our website at
GenBank accession numbers.
EST sequences, BU BU725997, BU BU714505, BU BU780918
and BU BU804512; full-length cDNAs, AY AY
Note: Supplementary information is available on the Nature Genetics website.

20. Systems

21. Gene networks
Lahav et al. Nat. Genet. 36, (2004) Dynamics of the p53-mdm2 feedback loop in individual cells.
Number of
digital pulses
varies with
DNA damage

22. Epigenomics

23. Heterochromatin from RNAi
Cam et al. July Comprehensive analysis of heterochromatin- and RNAi-
mediated epigenetic control of the fission yeast genome
Genome-wide chromatin immunoprecipitation on tiling 60-mer oligo arrays
Survey of histone H3 K4 and K9, heterochromatin proteins and RNAi machinery
Cloned RITS associated siRNAs
Supports active silencing of heterochromatic regions

24. Development

25. Analysis of developmental networks
Van Driessche et al. May Epistasis with global transcriptional
phenotypes
Phenotypes associated with Protein kinase A activity in Dictyostelium
Epistasis analysis performed on transcritptional profiles by microarray
Infer known and unknown regulatory hierarchies
Extends epistasis analysis to similar phenotypes

26. Human genome variation

27. Ancestry predicts genotype?
Jorde and Wooding. October 2004 Suppl.
Genetic variation, classification and ‘race’.
190 polymorphisms sequence variants of the angiotensinogen (AGT ) gene

28. Second human genome shows widespread copy number variation
Tuzun et al. July Fine-scale structural variation of the human genome
Sequences of fosmid end
pairs compared to finished genome sequence.
Verification by PCR and
aCGH
Published structural variants
of proven biomedical
importance
Common in population

30. Hypertension in pregnancy
Van Dijk et al. May Maternal segregation of the Dutch preeclampsia locus at 10q22 with a new member of the winged helix gene family
Allele sharing of sisters with pre-
eclampsia.
Maternal STOX1 gene is
expressed in invasive extravillus trophoblast
Five shared missense mutations
in maternal copy
Possible involvement in polyploidization

31. Natural selection on humans
Stefansson et al. February A common inversion under selection in Europeans.
900kb inversion polymorphism in 17q21.31 is at 20% in some European populations.
Largest block of extended linkage disequilibrium in the genome.
Perturbs meiotic linkage map.
Currently under selection, conferring 3% more offspring per generation in Iceland pedigrees.

32. Beneficial mutation
Cohen et al. February Low LDL cholesterol in individuals of African descent resulting from frequent nonsense mutations in PKS9
Up to 2% of African Americans and <0.1% of European Americans have missense mutations in the serine protease gene PKS9 which confers up to 40% lower serum LDL cholesterol.
The mutations were also found in Nigerian Yoruba speakers.

33. Technical reports
Ishkanian et al. Nat Genet. (AOP Feb 15th 2004). A tiling resolution microarray with complete coverage of the human genome
Useful for detecting microdeletions and amplified oncogenes