Genetic Variation: A Laboratory Manual is the first compendium of protocols specifically geared towards genetic variation studies, and includes thorough discussions on their applications for human and model organism studies. Intended for graduate students and professional scientists in clinical and research settings, it covers the complete spectrum of genetic variation—from SNPs and microsatellites to more complex DNA alterations, including copy number variation. Written and edited by leading scientists in the field, the early sections of the manual are devoted to study design and generating genotype data, the use of resources such as HapMap and dbSNP, as well as experimental, statistical, and bioinformatic approaches for analyzing the data. The final sections include descriptions of genetic variation in model organisms and discussions of recent insights into human genetic ancestry, forensics, and human variation.
Contents
1. Ethical Issues in Human Genetic Research: The Global Experience
K. Arnold and J. van der Walt
SECTION 1: STUDY DESIGN
Introduction
2. Population Choice as a Consideration for Genetic Analysis Study Design
J.C. Stephens and M. Bamshad
3. Power Calculations
D.M. Evans and S. Purcell
4. Genetic Anaylsis: Moving between Linkage and Association
A.V. Smith
5. NCBI dbSNP Database: Content and Searching
M.L. Feolo and S.T. Sherry
6. Using the HapMap Web Site
A.V. Smith
SECTION 2: LABORATORY PROTOCOLS
Introduction
PART 1: PREPARATION OF DNA AND RNA
7. Isolation of Plant DNA for Genotyping Analysis
N.M. Springer
8. Preparing RNA from Plant Tissues
A.-P. Hsia, H.D. Chen, K. Ohtsu, and P.S. Schnable
9. Preparing DNA from Mammalian Sources
A. Sahota, A.I. Brooks, and J.A. Tischfield
PART 2: SNP VARIATION ANALYSIS
10. Intermediate-Throughput Laboratory-Scale Genotyping Solutions
S.J. Macdonald
11. Intermediate-Throughput Laboratory-Scale Genotyping Protocols
E. Cuppen, S.J. Macdonald, C. Ha, P.-Y. Kwok, W.B. Barbazuk, A.-P. Hsia, H.D. Chen, Y. Fu, K. Ohtsu, and P.S. Schnable
12. Molecular Inversion Probes and Universal Tag Arrays: Application to Highplex Targeted SNP Genotyping
G. Karlin-Neumann, M. Sedova, R. Sapolsky, J. Forman, Y. Wang, M. Moorhead, and M.Faham
13. Whole-Genome Genotyping
S.B. Gabriel and M.P. Weiner
PART 3: COPY NUMBER AND COMPLEX VARIATION ANALYSIS
14. Comparative Genomic Hybridization to Detect Variation in the Copy Number of Large DNA Segments
I.N. Holcomb and B.J. Trask
15. Representational Oligonucleotide Microarray Analysis Detection of Genetic Variation
R. Lucito
16. Whole-Genome Sampling Analysis to Detect Copy Number Changes in FFPE Samples
S. Jacobs
17. Molecular Inversion Probe Targeted Genotyping: Application to Copy Number Determination
G.Karlin-Neumann, M. Sedova, R. Sapolsky, S. Lin, Y. Wang, M. Moorhead, and M. Faham
18. Microsatellite Markers for Linkage and Association Studies
J. Gulcher
SECTION 3: DATA ANALYSIS
Introduction
19. Considerations for SNP Selection
C. Carlson
20. Selection and Evaluation of tag-SNPs Using Tagger and HapMap
P. de Bakker
21. Haploview: Visualization and Analysis of SNP Genotype Data
J.C. Barrett
22. Considerations for Copy Number Analysis of FFPE Samples
S. Jacobs
23. Assessing Significance in Genetic Association Studies
M.J. Daly
24. Assessing Human Variation Data for Signatures of Natural Selection
M. Bamshad and J.C. Stephens
SECTION 4: VARIATION STUDIES IN MODEL ORGANISMS
Introduction
25. Arabidopsis
Y. Li and J.O. Borevitz
26. Maize
W.B. Barbazuk, A.-P. Hsia, H.D. Chen, Y. Fu, K. Ohtsu, and P.S. Schnable
27. Rice
H. Leung, K.L. McNally, and D. Mackill
28. The Mouse
C.M. Wade and M.J. Daly
29. The Rat
E. Cuppen, N. Hübner, H.J. Jacob, and A.E. Kwitek
30. The Cat
M.J. Lipinski, N. Billings, L.A. Lyons
31. The Dog
K. Lindblad-Toh and E.A. Ostrander
32. The Chimpanzee
T.S. Mikkelsen, M.C. Zody, and K. Lindblad-Toh
SECTION 5: INSIGHTS INTO HUMAN VARIATION
Introduction
33. Genealogical Markers: mtDNA and the Y Chromosome
M. Stoneking and M. Kayser
34. Forensic DNA Testing
J.M. Butler
35. The Human Genome: What Lies Ahead
M.P. Weiner and J.C. Stephens
APPENDIX: Cautions
INDEX