Science AI Journal
Biochemistry, Genetics and Molecular Biology · Research topic

Open research questions in Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities

35 unresolved questions extracted from the limitations and future-work sections of 313 Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities papers in our library. Each links back to the study that raised it.

What the literature leaves open

  • It is well established that there is a relationship between FMR1 gene and POI, however its connection with DOR and its implications remain unknown.

    The Frequency of the Fragile X Syndrome Intermediate Allele and Premutation in Women with Diminished Oocyte Reserve (Dor) vs Normal Oocyte Reserve (NOR) · 2026 · DOI

  • Article SummaryGenes in the Doublesex and mab-3 related (DMRT) family play important roles in sexual development across animals, but a comprehensive analysis of these transcription factors is lacking in the most basal mammalian lineage of monotremes.

    Monotremes provide novel insights into evolution of the DMRT gene family in vertebrates · 2026 · DOI

  • Although the gene CFAP65 has been implicated in MMAF, its full mutational spectrum and clinical relevance within highly consanguineous populations remain poorly characterized.

    A novel homozygous frameshift mutation in CFAP65 is associated with multiple morphological abnormalities of sperm flagella in a consanguineous Pakistani family · 2026 · DOI

  • Our findings refine current models of young and homomorphic sex chromosome evolution by showing how recombination suppression, restored recombination, and renewed differentiation can occur within the same population. Classical models explain why recombination suppression may evolve near sex-determining loci and why nonrecombining chromosomes can degenerate over long timescales. In R. temporaria, however, whole-genome resolution reveals a different dynamic: an older Dmrt1-linked sex-determining region is shared across all Y haplotypes, whereas the broad NRR/sex-linked regions are younger and have accumulated private mutations on distinct Y backgrounds. Thus, the unit of evolutionary continuity is not an entire Y chromosome, but a conserved sex-determining region surrounded by haplotype-specific histories of recombination suppression and X–Y differentiation. Under extreme heterochiasmy, large NRRs can arise rapidly; through sex-reversed XY females, X–Y recombination can be restored outside the sex-determining region; and subsequent transmission through males can again promote Y-specific differentiation. These cyclic dynamics of Y differentiation (Fig. 8b) help explain how frog sex chromosomes can remain homomorphic and evolutionarily labile despite episodes of extensive recombination suppression. This model makes several testable predictions. First, phased long-read assemblies should determine whether the shared 4.64 Mb region is maintained by an inversion, a supergene-like architecture, local recombination suppression without major structural rearrangement, or a combination of these. Second, controlled crosses involving sex-reversed XY females should test whether X–Y recombination is restored outside the Dmrt1-linked region and whether this exchange erodes Y-linked divergence. Third, early gonad-specific transcriptomic, epigenomic, and regulatory profiling should determine whether Dmrt1 acts through allele-specific regulatory divergence, dosage effects, structural variation, or linked regulatory elements. Fourth, population-genetic models incorporating sex reversal, extreme heterochiasmy, drift, migration, and sex-ratio selection should identify the conditions under which multiple Y haplotypes are transient versus maintained over longer timescales. Finally, comparative analyses across XY and ZW anurans, and across other taxa with strong heterochiasmy, should test whether heterochiasmy generally decouples the physical extent of recombination suppression from the age and degeneration of sex-linked regions. Overall, our results support a view of young sex chromosomes as dynamic population-genetic states rather than fixed evolutionary endpoints. In R. temporaria, coexisting Y haplotypes are not independent sex-determining systems and not successive steps along a single degeneration trajectory. They are divergent Y backgrounds anchored by a shared ancestral Dmrt1-linked region. This architecture links classical theory on recombination suppression and Y degeneration with models emphasizing recurrent X–Y recombination, shifting sex-linked boundaries, and reversible components of sex chromosome differentiation. It also provides a genome-wide framework for understanding how homomorphic sex chromosomes can persist for long periods in frogs and other lineages with labile sex determination, recurrent sex reversal, and extreme heterochiasmy.

    Coexisting Y haplotypes reveal cyclic sex chromosome differentiation around a shared sex-determining region · 2026 · DOI

  • While laboratory studies demonstrated that extreme thermal conditions induce female-to-male sex reversal (XX males), its occurrence in the wild remains unexplored, limiting our understanding of actual climate impacts.

    Thermally driven sex reversal reveals divergent sex determination dynamics in wild viviparous reptile populations · 2026 · DOI

  • Abstract Humans show reproducible sex differences in regional cortical volume (CV), but it remains unclear how these relate to the two biologically dissociable determinants of CV – surface area (SA) and cortical thickness (CT) – or to potentially causal sex chromosomal and gonadal effects.

    Regional sex differences in human cortical anatomy vary in their morphometric bases and overlap with sex chromosomal and gonadal influences · 2026 · DOI

  • Several limitations of this study should be acknowledged. First, all functional and transcriptomic experiments were performed in HEK293T cells, which do not express NR5A1 endogenously and lack the native gonadal chromatin context; therefore, the identified candidate targets require validation in more physiologically relevant cell models. Second, the transcriptomic and CUT&Tag analyses were restricted to the p.Gln329* truncating variant; the transcriptome‑wide consequences of the missense variants remain to be defined. Third, the assessment of subcellular localization was qualitative, and formal quantification of nuclear‑to‑cytoplasmic fluorescence ratios should be pursued in future studies. Finally, the small sample size limits robust genotype‑phenotype correlation, which will require larger multi‑center cohorts.

    Functional and transcriptomic insights into 46,XY disorders of sex development associated with NR5A1 gene variants · 2026 · DOI

  • This study investigated the role of SWI3A/B in regulating the transition from vegetative to sexual reproduction in Marchantia. Interpretation of the results, however, should take into account some experimental limitations. We generated 30 independent plant lines per sgRNA from three different sgRNAs. Of these 90 independent lines, only four carried mutations and in all cases in the promoter region. We hypothesize that MpSWI3A/B is an essential gene and future studies should hence consider a knock down or conditional knock out and methods such as cre/lox excision. Furthermore, the phenotypes observed in the overexpression lines may be confounded by potential consequences of overabundance (e.g. unspecific interaction with novel proteins) and interfering with the overall function of the SWI complex. As such, it is unclear at this stage, whether the phenotypes are gain- or loss-of-function and how accurately they represent biological roles of MpSWI3. The phenotypes may also be confounded by a non-clonal background of the spores in which mutations were generated, a limitation that remains to be addressed by generating mutations in the thallus stage. RNA-seq could also be conducted from various tissues and developmental stages to obtain a higher resolution. Future studies, including chromatin immunoprecipitation (ChIP-seq), will be essential to identify SWI3A/B target genes and clarify the molecular details of how MpSWI3 acts on sex determination in the bryophyte. Furthermore, genetic crosses evaluating the fertility of swi3a/boe-♂ would help determine, whether SWI3 influences not only reproductive development but also the alternation of generations in Marchantia.

    SWI3A/B regulates the transition from vegetative to reproductive phase in the liverwort Marchantia polymorpha · 2026 · DOI

  • The study used BLASTp searches with ARR17 (Potri.019G133600) and the newly proposed PI candidate sex determination gene as queries across Salix and Populus genomes, but the putative functional roles of sex-specific genes were inferred only from plant literature without experimental validation of their expression patterns during sex determination or developmental specificity in the sex-linked regions.

    Sex chromosome evolution mediated by a large inversion and a possible switch of the sex determination gene · 2026 · DOI

  • Pseudogenes on both W- and Z-haplotypes were identified using >80% sequence identity in conserved exons, but the evolutionary timeline of these pseudogene formations relative to the large inversion and potential sex determination gene switch (mentioned in the paper title) has not been reconstructed through detailed phylogenetic dating of these degenerative events.

    Sex chromosome evolution mediated by a large inversion and a possible switch of the sex determination gene · 2026 · DOI

  • The comparative analysis of female-specific polymorphisms was extended to only 3 additional Salix species (S. purpurea, S. suchowensis, S. viminalis) by mapping reads to the S. herbacea reference; testing whether identified female-specific sites and SNPs are conserved across the full Salix genus diversity and in distantly related dioecious plant genera would clarify the generalizability of the sex determination mechanism.

    Sex chromosome evolution mediated by a large inversion and a possible switch of the sex determination gene · 2026 · DOI

  • The ARR17 candidate sex determination gene was screened for intact homologs and partial duplicates across 10 Salix and Populus genome assemblies using 80% sequence identity cutoffs, but functional validation through knockdown or knockout experiments in Salix species to confirm ARR17's actual role in sex determination is absent.

    Sex chromosome evolution mediated by a large inversion and a possible switch of the sex determination gene · 2026 · DOI

  • The study identified female-specific SNPs and INDELs in S. herbacea sex-linked regions using a 0.3 minor allele read proportion threshold, but validation of this threshold's accuracy for distinguishing true sex-specific variants from sequencing artifacts in the complex duplicated sex-linked region (SLR) remains unexplored across different sequencing depths and read qualities.

    Sex chromosome evolution mediated by a large inversion and a possible switch of the sex determination gene · 2026 · DOI

  • The assembly and annotation pipeline did not characterize genomic islands of differentiation or candidate loci under selection related to heavy metal accumulation and parasite resistance, despite documented occurrence of these traits in wild S. melanotheron populations from polluted West African ecosystems. Population genomic scans using FST-based approaches should identify adaptive loci.

    Chromosome-level genome assembly of the blackchin tilapia (Sarotherodon melanotheron) · 2026 · DOI

  • The Hi-C scaffolding approach achieved chromosome-level assembly but did not investigate sex chromosome structure or sex-determining regions, despite evidence of environmental sex determination and biparental oral-brooding behavior variation in S. melanotheron populations. Comparative analysis of sex-linked genomic regions across environmental gradients should be performed.

    Chromosome-level genome assembly of the blackchin tilapia (Sarotherodon melanotheron) · 2026 · DOI

  • Gene annotation relied on ab initio prediction tools (AUGUSTUS, GlimmerHMM) and comparative genomics but lacks extensive RNA-seq data from tissues under salinity stress conditions. Transcriptome profiling of blackchin tilapia gill, kidney, and intestinal tissues exposed to freshwater versus marine environments should be conducted to validate and improve gene model accuracy for osmoregulatory genes.

    Chromosome-level genome assembly of the blackchin tilapia (Sarotherodon melanotheron) · 2026 · DOI

  • The transposable element annotation using RepeatModeler2 and RepeatMasker did not include functional characterization of mobile element insertions that may affect salinity-responsive gene regulation. Specific investigation of transposable elements near genes involved in the Gh/Igf endocrine system (previously identified as responsive to salinity challenges in S. melanotheron) is needed.

    Chromosome-level genome assembly of the blackchin tilapia (Sarotherodon melanotheron) · 2026 · DOI

  • The genome assembly was generated from a single individual blackchin tilapia specimen. Population-level genomic variation, including structural variants, copy number variations, and allelic diversity across wild populations from different West African coastal, estuarine, and freshwater ecosystems, remains uncharacterized and should be investigated using whole-genome sequencing of multiple population samples.

    Chromosome-level genome assembly of the blackchin tilapia (Sarotherodon melanotheron) · 2026 · DOI

  • The chromosome-level genome assembly of Sarotherodon melanotheron lacks comparative genomic analysis with other salinity-tolerant tilapia species to identify species-specific genomic regions associated with osmoregulation. Future work should perform synteny analysis and ortholog identification across S. melanotheron, Oreochromis niloticus, and other euryhaline cichlids to characterize the genetic basis of salinity tolerance.

    Chromosome-level genome assembly of the blackchin tilapia (Sarotherodon melanotheron) · 2026 · DOI

  • The relationship between STS gene deficiency and various neurobehavioral disorders including ADHD and autism spectrum disorder has been identified, but the specific molecular mechanisms linking STS deficiency to these neuropsychiatric manifestations remain unclear.

    A case report of X-linked ichthyosis associated with epilepsy due to an Xp22.31 deletion fragment · 2026 · DOI

  • Growing evidence suggests that growth impairment is an integral part of the clinical spectrum of Xp22.31 microdeletion syndrome, but the mechanisms by which loss of adjacent genes or regulatory elements contributes to developmental and growth delays requires further investigation.

    A case report of X-linked ichthyosis associated with epilepsy due to an Xp22.31 deletion fragment · 2026 · DOI

  • The majority of patients with XLI harbor larger deletions at Xp22.31 spanning multiple genes beyond STS, contributing to heterogeneous and complex clinical manifestations, indicating a need for better understanding of genotype-phenotype correlations across different deletion sizes.

    A case report of X-linked ichthyosis associated with epilepsy due to an Xp22.31 deletion fragment · 2026 · DOI

  • Abstract Sexual dimorphism evolves from sex-specific selective pressures and is often mediated by tissue-specific differential gene expression, although the mechanisms are not fully understood.

    Tissue-specific epigenetic and genetic regulation of sexual dimorphism · 2026 · DOI

  • In contrast, FOXL2, a key regulator of ovarian development and maintenance, has been relatively underexplored in canine studies.

    Canine XX DSD (SRY-negative): A Potential Role For The FOXL2 Gene · 2026 · DOI

  • Despite nearly a century of study, the identity of the causal gene remains controversial, partially due to previous inability to fully sequence the sex chromosomes.

    Two melanic pigment patterns are associated with a sex chromosome-linked oncogene in the mountain swordtail Xiphophorus nezahualcoyotl · 2026 · DOI

Most-cited papers in Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities

Most recent work

Find a gap in your own Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities sub-topic

This page shows what the Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities literature already flags as unresolved. To narrow it to your specific question, run the guided finder — it searches the gap library on demand and checks candidates against 250M+ OpenAlex works.

Open the Research Gap Finder →

Related topics in Biochemistry, Genetics and Molecular Biology

Gut microbiota and health
289 open questions
Single-cell and spatial transcriptomics
185 open questions
dental development and anomalies
121 open questions
Mitochondrial Function and Pathology
110 open questions
Genetic Associations and Epidemiology
106 open questions
Human-Animal Interaction Studies
105 open questions
Genomics and Chromatin Dynamics
97 open questions
Inflammatory Bowel Disease
91 open questions
35 open questions have been extracted from the limitations and future-work passages of 313 Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities papers in our library. Each one below links back to the study that raised it, so you can read the original claim in context.

Tools for your next paper

Gaps & Literature SearchFind open questions in any field — 120,000+ open gaps mined from our own library.Pre-CheckIs your paper ready? A Tier 1–5 acceptance probability in seconds.Journal FinderA ranked shortlist of target journals from a 17,500-venue index.Duplicate Publication CheckerCheck prior-publication & salami-slicing risk across 8 sources.Citation GeneratorFreeA DOI or title → APA, MLA, Vancouver, Chicago, BibTeX, RIS. No signup.Graphical Abstract MakerFreeTurn your findings into a colorblind-safe graphical abstract.

Compare the category — Honest roundups of the AI research tools, ours listed alongside the alternatives.

Command palette

Jump anywhere, run any action.