Mendelian Inheritance Revisited: Dominance and Recessiveness in Medical Genetics

Overview

Journal Nat Rev Genet

Specialty Genetics

Date 2023 Feb 22

PMID 36806206

Authors

Johannes Zschocke

Peter H Byers

Andrew O M Wilkie

Affiliations

Soon will be listed here.

Abstract

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.

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