<?xml version="1.0" encoding="UTF-8"?><xml><records><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Plender, Elizabeth G.</style></author><author><style face="normal" font="default" size="100%">Prodanov, Timofey</style></author><author><style face="normal" font="default" size="100%">Hsieh, Pinghsun</style></author><author><style face="normal" font="default" size="100%">Nizamis, Evangelos</style></author><author><style face="normal" font="default" size="100%">Harvey, William T.</style></author><author><style face="normal" font="default" size="100%">Sulovari, Arvis</style></author><author><style face="normal" font="default" size="100%">Munson, Katherine M.</style></author><author><style face="normal" font="default" size="100%">Kaufman, Eli J.</style></author><author><style face="normal" font="default" size="100%">O’Neal, Wanda K.</style></author><author><style face="normal" font="default" size="100%">Valdmanis, Paul N.</style></author><author><style face="normal" font="default" size="100%">Marschall, Tobias</style></author><author><style face="normal" font="default" size="100%">Bloom, Jesse D.</style></author><author><style face="normal" font="default" size="100%">Eichler, Evan E.</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Structural and genetic diversity in the secreted mucins MUC5AC and MUC5B</style></title><secondary-title><style face="normal" font="default" size="100%">American Journal of Human Genetics</style></secondary-title><short-title><style face="normal" font="default" size="100%">The American Journal of Human Genetics</style></short-title></titles><dates><year><style  face="normal" font="default" size="100%">2024</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2024/07/10/</style></date></pub-dates></dates><urls><web-urls><url><style face="normal" font="default" size="100%">https://www.sciencedirect.com/science/article/pii/S0002929724002131</style></url></web-urls></urls><isbn><style face="normal" font="default" size="100%">0002-9297</style></isbn><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;SummaryThe 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&amp;ndash;5,762 amino acids [aa]); however, seven haplotypes have expanded VNTRs (6,291&amp;ndash;7,019 aa). In contrast, 30 allelic variants of MUC5AC encode 16 distinct proteins (5,249&amp;ndash;6,325 aa) with cysteine-rich domain and VNTR copy-number variation. We group MUC5AC alleles into three phylogenetic clades: H1 (46%, &amp;sim;5,654 aa), H2 (33%, &amp;sim;5,742 aa), and H3 (7%, &amp;sim;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&amp;rsquo;s D analyses reveal that East Asians carry exceptionally large blocks with an excess of rare variation (p&amp;nbsp;&amp;lt;&amp;nbsp;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&amp;nbsp;&amp;lt;&amp;nbsp;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.&lt;/p&gt;
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