{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:01:18Z","timestamp":1785427278399,"version":"3.56.0"},"posted":{"date-parts":[[2026,7,4]]},"group-title":"Genetic and Genomic Medicine","reference-count":0,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T00:00:00Z","timestamp":1783123200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Human Genome Research Institute","award":["HG002385"],"award-info":[{"award-number":["HG002385"]}]},{"name":"National Human Genome Research Institute","award":["HG010169"],"award-info":[{"award-number":["HG010169"]}]},{"name":"National Human Genome Research Institute","award":["HG007497"],"award-info":[{"award-number":["HG007497"]}]},{"name":"National Human Genome Research Institute","award":["HG013748"],"award-info":[{"award-number":["HG013748"]}]},{"award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"https:\/\/ror.org\/006w34k90","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,7,4]]},"abstract":"<jats:p>\n                  Mucins are large glycoproteins that provide hydration and barrier function to epithelial tissues. Although genetically heterogeneous, all mucins harbor a large exon composed of variable number tandem repeats (VNTRs). Short-read sequencing has limited our understanding of mucin VNTR diversity and makes disease association studies challenging. We leverage 296 long-read phased genome assemblies to characterize 14 mucin family members, achieving \u226597% accuracy across 572 haplotypes. Phylogenetic haplogroup analysis reveals extraordinary structural heterozygosity, with\n                  <jats:italic>MUC4<\/jats:italic>\n                  harboring the greatest allelic diversity (n=240 distinct lengths) and\n                  <jats:italic>MUC12<\/jats:italic>\n                  the greatest size range (\u0394 = 55,233 bp; 23,080 amino acids). Ten mucins show significant population stratification (pFDR &lt; 0.05). At the\n                  <jats:italic>MUC4\/MUC20<\/jats:italic>\n                  locus, we characterize higher-order structural variation, including a recurrent inversion, copy number variation, and interlocus gene conversion. Optimized genotyping achieves \u226595% haplogroup concordance across 10 loci. We apply this to 4,637 deeply phenotyped cystic fibrosis patients and identify a significant association between short\n                  <jats:italic>MUC1<\/jats:italic>\n                  VNTRs and severe disease (p=0.0056), demonstrating the pangenome's utility for complex locus genotyping and disease discovery.\n                <\/jats:p>","DOI":"10.64898\/2026.07.01.26356476","type":"posted-content","created":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T14:00:14Z","timestamp":1783173614000},"source":"Crossref","is-referenced-by-count":0,"title":["Complex structural variation, phylogeny, and disease associations of the mucin pangenome"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5063-8737","authenticated-orcid":false,"given":"Elizabeth G","family":"Plender","sequence":"first","affiliation":[{"name":"University of Washington;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7469-6651","authenticated-orcid":false,"given":"Timofey","family":"Prodanov","sequence":"additional","affiliation":[{"name":"Heinrich Heine University;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiadong","family":"Lin","sequence":"additional","affiliation":[{"name":"University of Washington;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isaac","family":"Wong","sequence":"additional","affiliation":[{"name":"University of Washington;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Wertz","sequence":"additional","affiliation":[{"name":"University of Washington;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William W","family":"Gordon","sequence":"additional","affiliation":[{"name":"University of Washington;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J","family":"Bamshad","sequence":"additional","affiliation":[{"name":"University of Washington;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine M","family":"Munson","sequence":"additional","affiliation":[{"name":"University of Washington;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanda K","family":"O'Neal","sequence":"additional","affiliation":[{"name":"University of North Carolina at Chapel Hill Health Sciences Library: The University of North Carolina at Chapel Hill;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1267-3408","authenticated-orcid":false,"given":"Jesse D","family":"Bloom","sequence":"additional","affiliation":[{"name":"Fred Hutch Cancer Center;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Human Pangenome Reference Consortium","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9376-1030","authenticated-orcid":false,"given":"Tobias","family":"Marschall","sequence":"additional","affiliation":[{"name":"Heinrich Heine University, The University Hospital of Dusseldorf;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8246-4014","authenticated-orcid":false,"given":"Evan E","family":"Eichler","sequence":"additional","affiliation":[{"name":"Univ. of Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.07.01.26356476","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T14:00:14Z","timestamp":1783173614000},"score":1,"resource":{"primary":{"URL":"http:\/\/medrxiv.org\/lookup\/doi\/10.64898\/2026.07.01.26356476"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,4]]},"references-count":0,"URL":"https:\/\/doi.org\/10.64898\/2026.07.01.26356476","relation":{},"subject":[],"published":{"date-parts":[[2026,7,4]]},"subtype":"preprint"}}