Discovering genotypes underlying human phenotypes: past successes for mendelian disease, future approaches for complex disease

By David Botstein, N. Risch. Nature Genetics, 2003

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Citations in the corpus

Genotype Imputation (2009, background): “Both approaches have been highly successful in identifying genes responsible for single-gene Mendelian disorders (9).”
A survey of tools for variant analysis of next-generation genome sequencing data (2013, background): “Mendelian disorders Traditionally, the main approach to elucidate causes of Mendelian disorders has been positional cloning based on linkage analysis [29].”
Five years of GWAS discovery. (2012, background): “, singlegene disorders).(4) Mapping loci underlying common diseases and, in particular, identifying causative mutations have had much less success.”
Likelihood-Based Inference on Haplotype Effects in Genetic Association Studies (2006, background): “It is widely recognized that genetic dissection of complex human disorders requires large-scale association studies, which relate disease phenotypes to genetic variants, especially single nucleotide polymorphisms (SNPs) (Risch 2000; Botstein and Risch 2003).”
A missense single-nucleotide polymorphism in a gene encoding a protein tyrosine phosphatase (PTPN22) is associated with rheumatoid arthritis. (2004, neutral): “To identify genes involved in RA susceptibility, we investigated the association between putative functional single-nucleotide polymorphisms (SNPs) and RA among white individuals by use of a case-control study design; a second sample was tested for replication.”
The Integration of Genetic Propensities into Social-Control Models of Delinquency and Violence among Male Youths (2008, background): “Human geneticists have had remarkable success in identifying individual genes with variations that lead to simple Mendelian traits and diseases such as phenylketonuria (PKU), sickle-cell anemia, Tay-Sachs disease, and cystic fibrosis (Botstein and Risch 2003; Risch 2000).”
Chapter 4: Protein Interactions and Disease (2012, background): “based on its position in the chromosome by a process known as positional cloning [52].”
Network-based global inference of human disease genes (2008, background): “augmented or even supplanted traditional gene-mapping approaches (Botstein and Risch, 2003; McCarthy et al, 2003).”
Uncovering the roles of rare variants in common disease through whole-genome sequencing (2010, background): “However, this view is based on assumption, not observation, and it is possible that the variants that contribute to common diseases behave more like those that contribute to Mendelian diseases, in which the variants tend to have obvious effect”