Mendelian inheritance revisited: dominance and recessiveness in medical genetics

Understanding the consequences of genotype for phenotype (which ranges from molecule-level effects to whole-organism traits) is at the core of genetic diagnostics in medicine. Many measures of the deleteriousness of individual alleles exist, but these have limitations for predicting the clinical con...

Full description

Saved in:
Bibliographic Details
Published in:Nature reviews. Genetics 2023-07, Vol.24 (7), p.442-463
Main Authors: Zschocke, Johannes, Byers, Peter H., Wilkie, Andrew O. M.
Format: Article
Language:English
Subjects:
631/208/1516
631/208/2489/144
631/208/726/649
631/208/737
Agriculture
Alleles
Animal Genetics and Genomics
Biomedical and Life Sciences
Biomedicine
Cancer Research
Disease
DNA sequencing
Drug dosages
Gene Function
Genes
Genetic disorders
Genetic screening
Genetics
Genotype & phenotype
Genotypes
Heredity
Human Genetics
Medicine
Phenotypes
Proteins
Review Article
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Understanding the consequences of genotype for phenotype (which ranges from molecule-level effects to whole-organism traits) is at the core of genetic diagnostics in medicine. Many measures of the deleteriousness of individual alleles exist, but these have limitations for predicting the clinical consequences. Various mechanisms can protect the organism from the adverse effects of functional variants, especially when the variant is paired with a wild type allele. Understanding why some alleles are harmful in the heterozygous state — representing dominant inheritance — but others only with the biallelic presence of pathogenic variants — representing recessive inheritance — is particularly important when faced with the deluge of rare genetic alterations identified by high throughput DNA sequencing. Both awareness of the specific quantitative and/or qualitative effects of individual variants and the elucidation of allelic and non-allelic interactions are essential to optimize genetic diagnosis and counselling. This Review discusses the importance of understanding the mechanisms by which specific allelic variants and allelic combinations cause disease for accurately diagnosing, treating and counselling individuals with genetic disorders.
ISSN:1471-0056
1471-0064
DOI:10.1038/s41576-023-00574-0