Searching for genetic determinants in the new millennium

  title={Searching for genetic determinants in the new millennium},
  author={Neil Risch},
  • N. Risch
  • Published 15 June 2000
  • Biology
  • Nature
Human genetics is now at a critical juncture. The molecular methods used successfully to identify the genes underlying rare mendelian syndromes are failing to find the numerous genes causing more common, familial, non-mendelian diseases. With the human genome sequence nearing completion, new opportunities are being presented for unravelling the complex genetic basis of non-mendelian disorders based on large-scale genome-wide studies. Considerable debate has arisen regarding the best approach to… 
Discovering genotypes underlying human phenotypes: past successes for mendelian disease, future approaches for complex disease
The distribution of types of mutation in mendelian disease genes argues for serious consideration of the early application of a genomic-scale sequence-based approach to association studies and against complete reliance on a positional cloning approach based on a map of anonymous single nucleotide polymorphism haplotypes.
Searching for the regulators of human gene expression.
In two reports, Cheung and colleagues scale up human genetics analysis to an impressive level in a genome-wide search for the regulators of gene expression, performing linkage analysis on expression profiles for over 3,500 genes and employing the HapMap resource to take positive findings through to association studies at the genome- wide level.
The search for allelic variants that cause monogenic disorders or predispose to common, complex polygenic phenotypes
The challenge of the genetic medicine is now to decipher the nucleotide sequence variants that predispose to common complex, polygenic phenotypes.
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The Search for Genetic Variants and Epigenetics Related to Asthma
For the past two decades, a huge number of genetic studies have been conducted to identify the genetic variants responsible for asthma risk. Several types of genetic and genomic approaches, including
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In their Perspective, Risch and Merikangas propose that the power of the human genome project with association studies, a method for determining the basis of a genetic disease, can best accomplish the identification of the genetic basis of complex human diseases such as schizophrenia and diabetes.
Characterization of single-nucleotide polymorphisms in coding regions of human genes
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  • G. Thomson
  • Biology
    American journal of human genetics
  • 1995
With recent rapid advances in mapping of the human genome, including highly polymorphic and closely linked markers, studies of marker associations with disease are increasingly relevant for mapping
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Recently, attention has focused on the use of whole-genome linkage disequilibrium (LD) studies to map common disease genes. Such studies would employ a dense map of single nucleotide polymorphisms
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This Policy Forum, the authors call for a publicly supported effort to discover a large number of SNPs and to place the information in public databases.
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The performance of the genomic control method is quite good for plausible effects of liability genes, which bodes well for future genetic analyses of complex disorders.
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