Human disease genes

Jiménez‐Sánchez, Gerardo; Childs, Barton; Valle, David

doi:10.1038/35057050

Cited by 347 publications

(246 citation statements)

References 7 publications

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“…The recent completion of human genome sequencing [1] will fuel research aiming to identify genetic factors in the aetiology of disease [2]. Identification of such disease genes allows the development of genetic or DNA-tests to determine whether people are at risk of or affected by a disease [3,4].…”

Section: Introductionmentioning

confidence: 99%

Perceived genetic knowledge, attitudes towards genetic testing, and the relationship between these among patients with a chronic disease

Morren

Rijken

Baanders

et al. 2007

Patient Education and Counseling

111

163

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Objective: Genetics increasingly permeate everyday medicine. When patients want to make informed decisions about genetic testing, they require genetic knowledge. This study examined the genetic knowledge and attitudes of patients with chronic diseases, and the relationship between both. In addition, patients were asked about their preferred source of genetic information. Methods: Questionnaires were mailed to participants of a nationwide representative sample of patients with chronic diseases in the Netherlands (n = 1916). Results: The response rate was 82% (n = 1496). Perceived genetic knowledge was low, particularly among older and lower educated patients. Attitudes towards genetics were rather positive, especially among younger and higher educated patients. Some concerns were also documented, mainly about the consequences of genetic testing for employment and taking insurance. Patients who perceived to have little knowledge found it difficult to formulate an opinion about genetic testing. Higher levels of genetic knowledge were associated with a more favourable attitude towards genetics. Chronic patients prefer to receive genetic information from their GP. Conclusion: Chronic patients are ill prepared when they require genetic knowledge to make decisions regarding the treatment of their disease. This seems to result from a knowledge deficiency rather than from disagreement with the genetic developments. Practice implications: When chronic patients are in need of information about genetics or genetic testing, their general practitioner should provide this. #

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Section: Introductionmentioning

confidence: 99%

Perceived genetic knowledge, attitudes towards genetic testing, and the relationship between these among patients with a chronic disease

Morren

Rijken

Baanders

et al. 2007

Patient Education and Counseling

111

163

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“…Over 900 disease-associated human genes have been identified (Jimenez-Sanchez et al 2001). Although these genes are generally associated with specific functions, different domains within a given gene perform different roles related to the overall function of the protein product.…”

Section: Introductionmentioning

confidence: 99%

Quantifying the Intragenic Distribution of Human Disease Mutations

Miller

Parker²,

Rissing³

et al. 2003

Annals of Human Genetics

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SummaryA wide variety of functional domains exist within human genes. Since different domains vary in their roles regarding overall gene function, the ability for a mutation in a gene region to produce disease varies among domains. We tested two hypotheses regarding distributions of mutations among functional domains by using (1) sets of single nucleotide disease mutations for six genes (CFTR, TSC2, G6PD, PAX6, RS1, and PAH) and (2) sets of polymorphic replacement and silent mutations found in two genes (CFTR and TSC2). First, we tested the null hypothesis that sets of mutations are uniformly distributed among functional domains within genes. Second, we tested the null hypothesis that disease mutations are distributed among gene regions according to expectations derived from the distribution of evolutionary conserved and variable amino acid sites throughout each gene. In contrast to the mainly uniform distribution of sets of silent and polymorphic mutations, sets of disease mutations generally rejected the null hypotheses of both uniform and evolutionary-influenced distributions. Although the disease mutation data showed a better agreement with the evolutionary-derived expectations, disease mutations were found to be statistically overabundant in conserved domains, and under-represented in variable regions, even after accounting for amino acid site variability of domains over long-term evolutionary history. This finding suggests that there is a nonadditive influence of amino acid site conservation on the observed intragenic distribution of disease mutations, and underscores the importance of understanding the patterns of neutral amino acid substitutions permitted in a gene over long-term evolutionary history.

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“…D ecades-long efforts to map human disease loci, at first genetically and later physically (1), followed by recent positional cloning of many disease genes (2) and genome-wide association studies (3), have generated an impressive list of disorder-gene association pairs (4,5). In addition, recent efforts to map the protein-protein interactions in humans (6,7), together with efforts to curate an extensive map of human metabolism (8) and regulatory networks offer increasingly detailed maps of the relationships between different disease genes.…”

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confidence: 99%

The human disease network

Goh

Cusick

Valle

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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A network of disorders and disease genes linked by known disordergene associations offers a platform to explore in a single graphtheoretic framework all known phenotype and disease gene associations, indicating the common genetic origin of many diseases. Genes associated with similar disorders show both higher likelihood of physical interactions between their products and higher expression profiling similarity for their transcripts, supporting the existence of distinct disease-specific functional modules. We find that essential human genes are likely to encode hub proteins and are expressed widely in most tissues. This suggests that disease genes also would play a central role in the human interactome. In contrast, we find that the vast majority of disease genes are nonessential and show no tendency to encode hub proteins, and their expression pattern indicates that they are localized in the functional periphery of the network. A selection-based model explains the observed difference between essential and disease genes and also suggests that diseases caused by somatic mutations should not be peripheral, a prediction we confirm for cancer genes.biological networks ͉ complex networks ͉ human genetics ͉ systems biology ͉ diseasome

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Human disease genes

Cited by 347 publications

References 7 publications

Perceived genetic knowledge, attitudes towards genetic testing, and the relationship between these among patients with a chronic disease

Perceived genetic knowledge, attitudes towards genetic testing, and the relationship between these among patients with a chronic disease

Quantifying the Intragenic Distribution of Human Disease Mutations

The human disease network

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