Thoughts and a few refs about CNV
==================================

Questions:
=========

History:
   Karyotypes, deletion mapping  -- dates back to 1960s in  humans!
   
   Autosomal Deletion Mapping in Man
   Walter E. Nance and Eric Engel
   Science, New Series, Vol. 155, No. 3763 (Feb. 10, 1967), pp. 692-694

   1970s -- J. Stene did big (for those days) analyses of deletions,
        translocations, etc.  in foetuses.

Biology:
   What are they,  How big are they (length distribution)
   How are they distributed in genome,
   Inherited/novel ?

Technology
   How do we detect them.
   SNP genotyping arrays -- apparent homozygous segments,
                     decreased/increased intensity (Illumina)
   Family data: apparent Mendelian errors.

Health:
   Relationship to disease
   Causal or associated ?

----------------------------------------------------------------
A review paper:

Zhang F, Gu W, Hurles ME, Lupski JR.
Department of Molecular and Human Genetics,
Copy number variation in human health, disease, and evolution.
Annu Rev Genomics Hum Genet. 2009;10:451-81.

We would NOT want to read this one, but it contains a very large
number of references, some of which might be useful

-----------------------------------------------------------------

Detection:

Cooper GM, Zerr T, Kidd JM, Eichler EE, Nickerson DA.   (UW)
Systematic assessment of copy number variant detection 
via genome-wide SNP genotyping.
Nat Genet. 2008 Oct;40(10):1199-203. 

Other references from Greg Cooper: and to UW software
        HMMSeg (Bill Noble), SCIMM, SCOUT
-- earlier technologies :   CGH array methods

Yau C, Holmes CC.  (Oxford: Statistics)
CNV discovery using SNP genotyping arrays.
Cytogenet Genome Res. 2008;123(1-4):307-12. 

Next-generation sequencing:  (Kidd ref from Sarah, thanks!)

Alkan, Kidd, et al. et Eichler (2009)
Personalized copy number and segmental duplication maps using
next-generation sequencing.
Nat Genet 41; (Oct 2009);  1061-1068.


-------------------------------------------------------------------
Detection/distribution:

McCarroll et al. et Altshuler (Broad)
Integrated detection and population-genetic analysis of SNPs 
and copy number variation.
Nat Genet. 2008 Oct;40(10):1166-74. Epub 2008 Sep 7.

Korn et al. et Altshuler (Broad)
Integrated genotype calling and association analysis of SNPs, 
common copy number polymorphisms and rare CNVs.
Nat Genet. 2008 Oct;40(10):1253-60. Epub 2008 Sep 7.


Li Abscher; Science 2008.  HGDP.

------------------------------------------------------------------
Population-genetics and disease assoc refs (mostly from Sulgi -- Thanks!!)

Conrad et al. The population genetics of structural variation. Nat Genet.
2007

Scherer et al. Challenges and standards in integrating surveys of
structural variation. Nat Genet 2007

McCarroll et al. Copy-number variation and association studies of human
disease. Nat Genet 2007

Stranger et al. Relative impact of nucleotide and copy number variation
on gene expression phenotypes. Science 2007 

McCarroll Extending genome-wide association studies to copy-number
variation. Human Molecular Genetics 2008

Itsara et al. Population Analysis of Large Copy Number Variants and
Hotspots of Human Genetic Disease. AJHG 2009

-- disease associations :   Crohn's Disease, Epilepsy, Autism,
                             graft vs host (McCarrol)
---------------------------------------------------------------------