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Mendelian disorders deserve more attention

Nature Reviews Genetics volume 7, pages 277–282 (2006)Cite this article

Abstract

The study of inherited monogenic diseases has contributed greatly to our mechanistic understanding of pathogenic mutations and gene regulation, and to the development of effective diagnostic tools. But interest has gradually shifted away from monogenic diseases, which collectively affect only a small fraction of the world's population, towards multifactorial, common diseases. The quest for the genetic variability associated with common traits should not be done at the expense of Mendelian disorders, because the latter could still contribute greatly to understanding the aetiology of complex traits.

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Figure 1: Progress in disease-gene identification.

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Acknowledgements

We thank all the past and present members of our laboratories for ideas, debates and discussions. Mrs J. Amberger at OMIM, John Hopkins University, is gratefully acknowledged for her assistance in providing the data of figure 1a. S.E.A.'s laboratory is supported by the Swiss National Science Foundation (SNF), European Union, National Institutes of Health and the Lejeune and ChildCare Foundations. Work in J.S.B.'s laboratory is funded by grants from the SNF and the University of Lausanne.

Author information

Authors and Affiliations

  1. Department of Genetic Medicine and Development, University of Geneva Medical School, and University Hospital of Geneva, 1 rue Michel-Servet, Geneva, 1211, Switzerland

    Stylianos E. Antonarakis

  2. Department of Medical Genetics, University of Lausanne and Centre Hospitalier Universitaire Vaudois, 2 Avenue Pierre Decker, Lausanne, 1011, Switzerland

    Jacques S. Beckmann

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Related links

Related links

DATABASES

OMIM

Alzheimer disease

Bardet–Biedl syndrome

CHARGE syndrome

cystic fibrosis

Duchenne muscular dystrophy

facioscapulohumeral muscular dystrophy

Fanconi anaemia

hereditary prion disease

Lesch–Nyhan syndrome

limb girdle muscular dystrophy type 2B

Meckel syndrome

Miyoshi myopathy

Parkinson disease

sickle-cell anaemia

thalassaemias

FURTHER INFORMATION

Online Mendelian Inheritance in Man (OMIM)

Human Gene Mutation Database (HGMD)

The International Hapmap Project

Affymetrix

Illumina

Sequenom

The ENCODE Project

Glossary

Anticipation

A phenomenon that describes the property of some disorders to increase in severity in successive generations.

Copy-number polymorphism (CNP) or variant (CNV)

A structural genomic variant, resulting in confined copy-number changes in a defined chromosomal region. If its population allele frequency is less than 1%, then one refers to it as a variant; the term polymorphism refers instead to variants that occur at an allelic frequency of 1% or higher.

Discordant monozygotic twins

Twins that share identical genomes but are not affected with the same disorder; one twin being affected but the other not.

Epistatic interaction

The influence of the interaction of multiple loci on phenotypic variation.

Expressivity

The extent to which a genetic defect is expressed.

High-resolution tiling path CGH arrays

Arrays for comparative genomic hybridization (CGH) offering a resolution in the order of kilobases. The arrays are currently based on BACs or long oligonucleotides.

Mendelian disease

A disease for which alternative genotypes fall into distinct, discrete phenotypic classes, following Gregor Mendel's laws of inheritance.

Monogenic disorder

A disease that is mainly caused by variants in a single gene.

Multifactorial

Multifactorial traits are determined by a combination of genetic as well as non-genetic factors, each contributing to the overall phenotype.

Parental imprinting

Differential allele expression that depends on parental origin.

Penetrance

The frequency with which a given genotype manifests itself in a given phenotype.

Triplet-repeat copy number

Triplet-repeat copy-number mutations are dynamic mutations that are due to the expansion or contraction in the number of triplet nucleotide repeats.

Uniparental disomy

(UPD). A state wherein both homologues (alleles) at a locus derive from the same parent; for some chromosomal segments, UPD generates characteristic syndromes.

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Antonarakis, S., Beckmann, J. Mendelian disorders deserve more attention. Nat Rev Genet 7, 277–282 (2006). https://doi.org/10.1038/nrg1826

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