ArticleAmerican journal of human genetics2024
Structural and genetic diversity in the secreted mucins MUC5AC and MUC5B.
Article in American journal of human genetics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Pooled it
- Complex structural variation, phylogeny, and disease associations of the mucin pangenome.medRxiv : the preprint server for health sciences · 2026Article
- Recurrent structural variation and recent turnover at the 17q21.31 locus in humans and great apes.Nature communications · 2026Article
- Treatment of pulmonary fibrosis: From disease mechanisms to future novel therapies (Review).International journal of molecular medicine · 2026Review
- Ancient DNA reveals that natural selection has upregulated the immune system over the last 10,000 years.bioRxiv : the preprint server for biology · 2026Article
- Population-level structural variant characterization using pangenome graphs.Nature genetics · 2026Article
- Early Transcriptomic Response of Human Iris Stromal Cells During Herpes Simplex Virus Entry Reveals Interplay Between Cell Glycocalyx and Viral Exploitation.International journal of molecular sciences · 2026Article
- Evolutionary Balancing of Genetic Consequence and Innovation in Mammals Through Variable Number Tandem Repeats.Genome biology and evolution · 2026Review
- Maintenance and disruption of mucous barrier homeostasis: the critical role of MUC5AC/MUC5B balance in airway diseases.Frontiers in medicine · 2026Review
- Locityper enables targeted genotyping of complex polymorphic genes.Nature genetics · 2025Article
- Multiple roles and mechanisms of MUC6 in cancer (Review).International journal of molecular medicine · 2025Review
- Recurrent structural variation and recent turnover at the 17q21.31 locus in humans and great apes.bioRxiv : the preprint server for biology · 2025Article
- Article
- TheScience (New York, N.Y.) · 2025Article
- Human-specific gene expansions contribute to brain evolution.bioRxiv : the preprint server for biology · 2025Article
- Mucins and Their Roles in Asthma.Immunological reviews · 2025Review
- MUC5AC filaments illuminate the structural diversification of respiratory and intestinal mucins.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Deciphering the role of structural variation in human evolution: a functional perspective.Current opinion in genetics & development · 2024Review
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13 authors.
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Abstract
The secreted mucins MUC5AC and MUC5B are large glycoproteins that play critical defensive roles in pathogen entrapment and mucociliary clearance. Their respective genes contain polymorphic and degenerate protein-coding variable number tandem repeats (VNTRs) that make the loci difficult to investigate with short reads. We characterize the structural diversity of MUC5AC and MUC5B by long-read sequencing and assembly of 206 human and 20 nonhuman primate (NHP) haplotypes. We find that human MUC5B is largely invariant (5,761-5,762 amino acids [aa]); however, seven haplotypes have expanded VNTRs (6,291-7,019 aa). In contrast, 30 allelic variants of MUC5AC encode 16 distinct proteins (5,249-6,325 aa) with cysteine-rich domain and VNTR copy-number variation. We group MUC5AC alleles into three phylogenetic clades: H1 (46%, ∼5,654 aa), H2 (33%, ∼5,742 aa), and H3 (7%, ∼6,325 aa). The two most common human MUC5AC variants are smaller than NHP gene models, suggesting a reduction in protein length during recent human evolution. Linkage disequilibrium and Tajima's D analyses reveal that East Asians carry exceptionally large blocks with an excess of rare variation (p < 0.05) at MUC5AC. To validate this result, we use Locityper for genotyping MUC5AC haplogroups in 2,600 unrelated samples from the 1000 Genomes Project. We observe a signature of positive selection in H1 among East Asians and a depletion of the likely ancestral haplogroup (H3). In Europeans, H3 alleles show an excess of common variation and deviate from Hardy-Weinberg equilibrium (p < 0.05), consistent with heterozygote advantage and balancing selection. This study provides a generalizable strategy to characterize complex protein-coding VNTRs for improved disease associations.
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