{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:05:25Z","timestamp":1785409525234,"version":"3.56.0"},"posted":{"date-parts":[[2024,8,11]]},"group-title":"Genomics","reference-count":74,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2024,8,11]],"date-time":"2024-08-11T00:00:00Z","timestamp":1723334400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"award":["R01HG011649"],"award-info":[{"award-number":["R01HG011649"]}],"id":[{"id":"https:\/\/ror.org\/00baak391","id-type":"ROR","asserted-by":"publisher"}]},{"award":["U01HG010973."],"award-info":[{"award-number":["U01HG010973."]}],"id":[{"id":"https:\/\/ror.org\/00baak391","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,4,13]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Copy number variant (CNV) genes are important in evolution and disease, yet sequence variation in CNV genes remains a blind spot in large-scale studies. We present ctyper, a method that leverages pangenomes to produce allele-specific copy numbers with locally phased variants from next-generation sequencing (NGS) reads. Benchmarking on 3,351 CNV genes, including\n                  <jats:italic>HLA<\/jats:italic>\n                  ,\n                  <jats:italic>SMN<\/jats:italic>\n                  , and\n                  <jats:italic>CYP2D6<\/jats:italic>\n                  , and 212 challenging medically relevant (CMR) genes that are poorly mapped by NGS, ctyper captures 96.5% of phased variants with \u226599.1% correctness of copy number on CNV genes and 94.8% of phased variants on CMR genes. Applying alignment-free algorithms, ctyper requires 1.5 hours per genome on a single CPU. The results largely improve predictions of gene expression compared to known expression quantitative trait loci (eQTL) variants. Allele-specific expression quantified divergent expression on 7.94% of paralogs and tissue-specific biases on 4.68% of paralogs. We found reduced expression of\n                  <jats:italic>SMN2<\/jats:italic>\n                  due to\n                  <jats:italic>SMN1<\/jats:italic>\n                  conversion, potentially affecting spinal muscular atrophy, and increased expression of translocated duplications of\n                  <jats:italic>AMY2B<\/jats:italic>\n                  . Overall, ctyper enables biobank-scale genotyping of CNV and CMR genes.\n                <\/jats:p>","DOI":"10.1101\/2024.08.11.607269","type":"posted-content","created":{"date-parts":[[2024,8,11]],"date-time":"2024-08-11T23:25:24Z","timestamp":1723418724000},"source":"Crossref","is-referenced-by-count":0,"title":["Genotyping sequence-resolved copy number variation using pangenomes reveals paralog-specific global diversity and expression divergence of duplicated genes"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8650-5541","authenticated-orcid":false,"given":"Walfred","family":"Ma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5395-1457","authenticated-orcid":false,"given":"Mark JP","family":"Chaisson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025052500124474000_2024.08.11.607269v6.1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1197005"},{"key":"2025052500124474000_2024.08.11.607269v6.2","doi-asserted-by":"publisher","DOI":"10.1038\/nature05329"},{"key":"2025052500124474000_2024.08.11.607269v6.3","unstructured":"Mac\u00e9, A. et al. CNV-association meta-analysis in 191,161 European adults reveals new loci associated with anthropometric traits. Nat. 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