Scope

Advancement of genetic and genomic technologies in recent years has highlighted how human traits and diseases are underscored by diverse genetic architecture forming a continuum ranging from rare variants of large effect, to common variants with small effect. The Genetic Disorders section publishes high-quality research probing the genetic basis of disease, irrespective of whether the disease falls under the traditional labels of Mendelian disorder, complex disease (or related quantitative trait), or oligogenic phenomena that fall somewhere in between. The section encourages multidisciplinary genetic studies that intersect with cell and molecular biology approaches, model organisms, or systems biology applications aimed at elucidating underlying mechanism and therapeutic avenues. Studies exploring variable penetrance, variable expressivity, or gene by environment interaction are also welcome.

Specifically this section publishes:

-     Human genetic studies of a wide range of disorders and related disease-relevant traits. These include, but are not limited to: (1) prenatal and reproductive genetics; (2) Mendelian disorders; (3) complex traits and polygenic disorders; (4) cancer genetics; and (5) epigenetics.

-     Genetic and genomic studies describing new causal or contributory loci with priority for research including mechanistic follow-up employing in vitro or in vivo model systems.

-     Novel computational approaches applied to the dissection of human genetic disease.

-     Translational studies including novel diagnostics, therapeutic target identification, or preclinical studies.

Please see the guidelines about content and novelty below. We welcome manuscripts fulfilling the following criteria:

Mendelian traits:

1. New causal gene explaining a phenotype or disorder in one or more families. Findings should be accompanied by adequate support for causality, especially when the gene discovery is reported in a single family. For discoveries in single families, support for causality must include experimental models (in vivo and/or in vitro) and should also be supported by population genetics and in silico modelling.

2. New mechanistic insights about a known gene or variant. These findings need to be supported by experimental data and not just in silico predictions. Transcriptomic, proteomic, or novel model organism studies are welcomed and encouraged.

3. Mutational analysis of a known gene in a novel disease cohort and reporting of allelic contribution whether it be novel or known alleles. A review of new results in the context of existing cohorts is especially important to compare what is currently known about the disorder.

4. New case reports are welcomed as long as they conform to the article type definition which can be found here.

5. New diagnostic approach (known or novel gene set). If the approach focuses on a known gene set, a comparison against existing strategies to highlight strengths and limitations is required.

6. New digenic or oligogenic phenomena. Studies with multiple families are preferred, but if reported in one family, strong genetics and functional support are required for further consideration.

Complex traits:

1. Study design and power. A study should have adequate sample size to have sufficient power to allow detection of the effect sizes we now expect given current understanding of the genetic architecture of complex traits. The power of the study should be explicitly stated.

2. Statistical significance. Unless testing a locus with very strong prior evidence (i.e. already robustly associated with a particular trait at stringent significance thresholds, normally p<5x10-8) in a new setting, any claims for novel association should minimally meet Bonferroni multiple testing corrected p-value thresholds. If claiming a completely novel association this would normally be p<5x10-8, findings not meeting this stringent threshold should be carefully placed as "suggestive" or meriting additional follow-up.

3. Studies replicating previously established associations in new population ancestries/ new interesting cohorts are welcome. Replication of a well-established locus in a population of similar ancestry and phenotype would not normally be considered unless there is considerable new biological insight gained from the study. This could take the form of description of a new variant likely to be causal, new mechanistic insight, link with a new phenotype (including molecular phenotypes such as other "omics" data).

4. Studies of well replicated loci but with the addition of new functional data or clinical insights are welcome.

5. Provided the study design is adequate, the study has been well conducted and is scientifically sound, "negative" findings are acceptable. Interpretation of what the "negative" results imply is however necessary, i.e., explain power limitations.

Other examples (as applied to Mendelian or complex traits): 

1. New therapeutic approach applied to cells or animals on an established disease model.

2. Known therapeutic approach applied to a new disease model.

------------------------------------------------------------------------

Founding Specialty Chief Editor: Jumana Y Al-Aama, King Abdulaziz University, Jeddah, Saudi Arabia.

Submission

Copyright Statement