Understanding the inheritance patterns of genes is particularly significant in the context of genetic diseases. The identification and classification of these patterns provide valuable insights into the likelihood of a genetic variant causing a disease. By incorporating zygosity and gene inheritance information, the iFlow workflows assign specific inheritance pattern matches to identified variants. This comprehensive approach enables a better understanding of the genetic underpinnings of diseases, facilitating more accurate diagnoses and personalized treatment strategies.
Every individual possesses two copies of each autosomal gene, one inherited from their mother and one from their father. The inheritance patterns determine how the genetic traits are passed down from one generation to another and how they impact the individual's phenotype. Inheritance modes differ between autosomal and sex chromosomes, because females carry two copies of each X-linked gene, while males carry only one copy each of X-linked and Y-linked genes. The basic modes of inheritance include:
Determining the inheritance pattern of a gene or mutation is particularly significant in the context of diseases. Specifically, it helps determine whether an inherited genetic variant is dominant enough to cause the development of a disease. The HPO and OMIM databases collect information on the identified inheritance patterns of genes.
Within the iFlow workflows, we assign an inheritance pattern match to each identified variant. We consider zygosity (GATK HaplotypeCaller) and the gene inheritance pattern (HPO database). This information indicates whether the patient's genotype is a probable cause of the disease, given the inheritance pattern of the damaged gene. We identify the following categories:
The assignment of an inheritance pattern match serves as a valuable tool for evaluating the potential contribution of a specific variant to disease symptoms. The inheritance pattern match can be used to assess the likelihood that given variant is indeed causing the disease symptoms. For instance, when a recessive inheritance pattern is identified, a pathogenic variant in a heterozygous gene is less likely to be responsible for the observed symptoms. Conversely, if a likely pathogenic variant or a variant of uncertain significance is found in a homozygous state or exhibits a dominant inheritance mode, it is more likely to exert a significant impact on the individual's phenotype and disease symptoms.
Ref
Köhler et al (2021) The Human Phenotype Ontology in 2021, Nucleic Acids Research, Volume 49, Issue D1, 8 January 2021, Pages D1207–D1217, https://doi.org/10.1093/nar/gkaa1043Online Mendelian Inheritance in Man, OMIM, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University (Baltimore, MD) https://omim.org/
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