Journal ArticleDOI
Association study designs for complex diseases
Lon R. Cardon,John I. Bell +1 more
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TLDR
With the discovery of massive numbers of genetic markers and the development of better tools for genotyping, association studies will inevitably proliferate and now is the time to consider critically the design of such studies to avoid the mistakes of the past and to maximize their potential to identify new components of disease.Abstract:
Assessing the association between DNA variants and disease has been used widely to identify regions of the genome and candidate genes that contribute to disease. However, there are numerous examples of associations that cannot be replicated, which has led to skepticism about the utility of the approach for common conditions. With the discovery of massive numbers of genetic markers and the development of better tools for genotyping, association studies will inevitably proliferate. Now is the time to consider critically the design of such studies, to avoid the mistakes of the past and to maximize their potential to identify new components of disease.read more
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Book ChapterDOI
Genetics of Idiopathic Male Infertility
TL;DR: By using a comparative cross-species approach, major susceptibility genes underlying male infertility can be identified in association studies and a candidate-gene approach that incorporates biological information from model organisms is likely to be critical in deciphering the genetic basis of idiopathic male fertility.
Journal ArticleDOI
Integrating genetic and toxicogenomic information for determining underlying susceptibility to developmental disorders
TL;DR: Using NTDs as an example of developmental disorder, it is shown how simple integration of genetic information from previous studies into the standard microarray design can enhance analysis of gene-environment interactions to better define environmental exposure-disease pathways in sensitive and resistant mouse strains.
Journal ArticleDOI
An overview of the environmental genome project.
D. A. Nickerson,M. J. Rieder,Dana C. Crawford,C. S. Carlson,R. J. Livingston,Thomas J. Goehl +5 more
TL;DR: This symposium explored the feasibility of the Environmental Genome Project (EGP), designed to explore the relationship between common genetic polymorphisms and environmentally induced disease in human populations.
Book ChapterDOI
Genetic Regulation of the Variation in Pubertal Timing
Craig A. Hodges,Mark R. Palmert +1 more
TL;DR: In this chapter, data supporting the heritability of pubertal timing, investigative approaches, and progress that has been made in identifying the genetic factors that regulate puberal timing are discussed.
Journal ArticleDOI
Designing optimally multiplexed SNP genotyping assays
TL;DR: This work addresses the optimization problem of designing assays that maximize the number of genotyped SNPs, subject to the multiplexing constraints, and provides essentially optimal heuristics for solving the corresponding coloring problem.
References
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TL;DR: In this article, the authors used haplotype analysis of linkage disequilibrium to spotlight a small segment of 4p16.3 as the likely location of the defect, which is expanded and unstable on HD chromosomes.
Journal Article
A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. The Huntington's Disease Collaborative Research Group.
Manish A. Shah,Nicole A. Datson,Lakshmi Srinidhi,Vincent P. Stanton,Marcy E. MacDonald,Marc W. Allard,S. Youngman,Anna-Maria Frischauf,Richard Mott,KM Draths,Günther Zehetner,C. O’Donovan,Thomas J. Fielder,Bruce G. Jenkins,Manju Swaroop,Sherryl A.M. Taylor,Lynn Doucette-Stamm,Heather MacFarlane,Scott A. Strobel,H. E. McFarlane,Alan Buckler,Nicolet Groot,Holger Hummerich,Deanna M. Church,M. A. Anderson,Marianne James,Glenn Barnes,M. Christine,Francis S. Collins,Mabel P. Duyao,Peter B. Dervan,Gillian P. Bates,T Holloway,Peter S. Harper,TW Mcdonald,M North,K Blanchard,John J. Wasmuth,D. Shaw,Hans Lehrach,Danilo A. Tagle,Annemarie Poustka,David E. Housman,T. Huntington,Zdenek Sedlacek,Laura Riba,Susan F. Kirby,Carol Lin,Richard H. Myers,Leslie M. Thompson,Russell G. Snell,Michael Conlon O'Donovan,K Gillespie,Rita Shiang,Nancy S. Wexler,Christine Ambrose,J. F. Gusella,Sarah Baxendale,N. Groat,John Valdes +59 more
TL;DR: The Huntington's disease mutation involves an unstable DNA segment, similar to those described in fragile X syndrome, spino-bulbar muscular atrophy, and myotonic dystrophy, acting in the context of a novel 4p16.3 gene to produce a dominant phenotype.
Journal ArticleDOI
Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA.
John R. Riordan,Johanna M. Rommens,Batsheva Kerem,Noa Alon,Richard Rozmahel,Zbyszko Grzelczak,Julian Zielenski,Si Lok,Natasa Plavsic,Jia Ling Chou,Mitchell L. Drumm,Michael C. Iannuzzi,Francis S. Collins,Lap-Chee Tsui +13 more
TL;DR: A deletion of three base pairs that results in the omission of a phenylalanine residue at the center of the first predicted nucleotide-binding domain was detected in CF patients.
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