Related Experiment Video
Updated: Jun 20, 2026
09:37
Navigating MARRVEL, a Web-Based Tool that Integrates Human Genomics and Model Organism Genetics Information
Published on: August 15, 2019
Atypical Biallelic Inheritance in "Dominant" Genes: Evidence From a Large-Scale Consanguineus Exome Cohort.
Elifcan Taşdelen1, Umut Can Tekbaş1, Abdulkerim Kolkıran2
1Department of Medical Genetics, Ankara Etlik City Hospital, Ankara, Turkiye.
American Journal of Medical Genetics. Part A
|June 19, 2026
Summary
Biallelic variants in dominant genes cause rare disorders in consanguineous families, revealing a dosage-sensitive inheritance continuum. This finding improves diagnosis for Mendelian diseases.
Area of Science:
- Genetics
- Molecular Biology
- Medical Genetics
Background:
- Exome sequencing (ES) aids Mendelian disease diagnosis.
- Biallelic variants in dominant genes are underrecognized in consanguineous populations.
Purpose of the Study:
- Characterize clinical/molecular features of biallelic dominant variants.
- Explore pathway-level patterns of dual inheritance.
- Investigate mechanisms of disease in consanguineous families.
Main Methods:
- Retrospective review of exome data from 1450 individuals (2022-2024).
- Filtered biallelic variants in OMIM autosomal dominant genes.
- Pathway analysis (Gene Ontology, STRING) and gnomAD constraint metrics.
Main Results:
- Five consanguineous families had biallelic variants in dominant genes (~3.1% of homozygous pathogenic variants).
- Identified mechanisms: hypomorphic, semidominant dosage sensitivity, structural effects, loss of function.
- Pathway analysis showed dosage sensitivity in telomere maintenance, ECM, Wnt/BMP signaling, and histone modification.
Conclusions:
- Autosomal dominant genes can cause disease biallelically, indicating a dosage-sensitive continuum.
- Dual inheritance patterns are driven by gene dosage and functional impact.
- Integrating these analyses refines rare disorder inheritance understanding, especially in consanguineous groups.
Related Concept Videos
01:11Genetic Lingo
Overview
01:35Pedigree Analysis
Overview
01:11Genome-wide Association Studies-GWAS
Genome-wide association studies or GWAS are used to identify whether common SNPs are associated with certain diseases. Suppose specific SNPs are more frequently observed in individuals with a particular disease than those without the disease. In that case, those SNPs are said to be associated with the disease. Chi-square analysis is performed to check the probability of the allele likely to be associated with the disease.
GWAS does not require the identification of the target gene involved in...
GWAS does not require the identification of the target gene involved in...
01:43Incomplete Dominance
Gregor Mendel's work (1822 - 1884) was primarily focused on pea plants. Through his initial experiments, he determined that every gene in a diploid cell has two variants called alleles inherited from each parent. He suggested that amongst these two alleles, one allele is dominant in character and the other recessive. The combination of alleles determines the phenotype of a gene in an organism.
01:19X-linked Traits
In most mammalian species, females have two X sex chromosomes and males have an X and Y. As a result, mutations on the X chromosome in females may be masked by the presence of a normal allele on the second X. In contrast, a mutation on the X chromosome in males more often causes observable biological defects, as there is no normal X to compensate. Trait variations arising from mutations on the X chromosome are called “X-linked”.
01:19X-linked Traits
In most mammalian species, females have two X sex chromosomes and males have an X and Y. As a result, mutations on the X chromosome in females may be masked by the presence of a normal allele on the second X. In contrast, a mutation on the X chromosome in males more often causes observable biological defects, as there is no normal X to compensate. Trait variations arising from mutations on the X chromosome are called “X-linked”.