Genetic Heterogeneity in Human Disease

@article{McClellan2010GeneticHI,
  title={Genetic Heterogeneity in Human Disease},
  author={Jon M McClellan and Mary-Claire King},
  journal={Cell},
  year={2010},
  volume={141},
  pages={210-217}
}

Figures from this paper

Human genetic susceptibility to infectious disease
TLDR
Insight is provided into the genetic architecture of infectious disease susceptibility and immune molecules and pathways that are directly relevant to the human host defence are identified.
De novo mutations in human genetic disease
TLDR
Recent findings suggesting that de novo mutations play a prominent part in rare and common forms of neurodevelopmental diseases, including intellectual disability, autism and schizophrenia are discussed.
Heuristic Methods for Finding Pathogenic Variants in Gene Coding Sequences
TLDR
These are exciting times, with a plethora of new technologies that are expediting discovery of the genetic underpinnings of human disease, allowing each person's entire genetic makeup to be revealed.
Pleiotropy of Presenilins
TLDR
Pleiotropy gene presenilins, mutations in which have been detected in three genetically heterogeneous diseases: early-onset familial Alzheimer’s disease, familial or sporadic dilated cardiomyopathy, and familial hidradenitis suppurativa are described.
Genomic analysis of mental illness: a changing landscape.
TLDR
The degree of heterogeneity in schizophrenia and other complex neuropsychiatric disorders is so great that most unrelated patients may have a different genetic cause, which has fundamental implications for translational and interventional research.
The fog of genetics: what is known, unknown and unknowable in the genetics of complex traits and diseases
A major task for genetics is searching for genetic variants associated with disease. But we may well be missing a large number of "unknown unknown" alleles in the "fog of genetics".
Genetics of Human Cardiovascular Disease
Whole Exome Sequencing Identifies Rare Protein‐Coding Variants in Behçet's Disease
TLDR
Investigation of the role of rare variants in Behçet's disease by performing whole exome sequencing in patients of European descent finds several common genetic variants associated with BD have been less explored.
Unlocking Mendelian disease using exome sequencing
Exome sequencing is revolutionizing Mendelian disease gene identification. This results in improved clinical diagnosis, more accurate genotype-phenotype correlations and new insights into the role of
...
...

References

SHOWING 1-10 OF 100 REFERENCES
Rare Variants Create Synthetic Genome-Wide Associations
TLDR
A simulation study shows that rare variants with much greater impacts on disease risk may be responsible for some of the associations with very modest increases of risk for various common diseases.
The Future of Genetic Studies of Complex Human Diseases
TLDR
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.
Isolated populations and complex disease gene identification
The utility of genetically isolated populations (population isolates) in the mapping and identification of genes is not only limited to the study of rare diseases; isolated populations also provide a
Finding the missing heritability of complex diseases
Genome-wide association studies have identified hundreds of genetic variants associated with complex human diseases and traits, and have provided valuable insights into their genetic architecture.
Common genetic variation and human traits.
Researchers now know how to properly account for most of the multiple hypothesis testing involved in mining the genome for associations, and most reported associations reflect real biologic
Strong association of de novo copy number mutations with sporadic schizophrenia
TLDR
The results suggest that rare de novo germline mutations contribute to schizophrenia vulnerability in sporadic cases and that rare genetic lesions at many different loci can account, at least in part, for the genetic heterogeneity of this disease.
The allelic architecture of human disease genes: common disease-common variant...or not?
TLDR
This article reviews the available data and models relating to the number and frequencies of susceptibility alleles at complex disease loci-the 'allelic architecture' of human disease genes and shows that the predicted frequency spectrum of disease variants at a gene depends crucially on the method of ascertainment.
Autism: Many Genes, Common Pathways?
Patterns of human genetic diversity: implications for human evolutionary history and disease.
TLDR
Comparative studies across ethnically diverse human populations and across human and nonhuman primate species is important for reconstructing human evolutionary history and for understanding the genetic basis of human disease.
Rare Structural Variants Disrupt Multiple Genes in Neurodevelopmental Pathways in Schizophrenia
TLDR
The results suggest that multiple, individually rare mutations altering genes in neurodevelopmental pathways contribute to schizophrenia, and disrupted genes disproportionately from signaling networks controlling neurodevelopment, including neuregulin and glutamate pathways.
...
...