{"entity": "researcher", "timestamp": "2026-09-23T21:55:19.628Z", "family": "Grochowski", "given": "Christopher M", "initials": "CM", "orcid": "0000-0002-3884-7720", "affiliations": ["Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/88a70acbf92744869c3e9c067f5278a6.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/88a70acbf92744869c3e9c067f5278a6"}}, "publications": [{"entity": "publication", "iuid": "1439ad651dd840bc89fa61ac9d2add3a", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/1439ad651dd840bc89fa61ac9d2add3a.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/1439ad651dd840bc89fa61ac9d2add3a"}}, "title": "Leveraging the T2T assembly to resolve rare and pathogenic inversions in reference genome gaps.", "authors": [{"family": "Bilgrav Saether", "given": "Kristine", "initials": "K"}, {"family": "Eisfeldt", "given": "Jesper", "initials": "J"}, {"family": "Bengtsson", "given": "Jesse D", "initials": "JD"}, {"family": "Lun", "given": "Ming Yin", "initials": "MY"}, {"family": "Grochowski", "given": "Christopher M", "initials": "CM", "orcid": "0000-0002-3884-7720", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/88a70acbf92744869c3e9c067f5278a6.json"}}, {"family": "Mahmoud", "given": "Medhat", "initials": "M", "orcid": "0000-0002-2553-4231", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/32766ce1fbaa42d0ad083e06294b5ef5.json"}}, {"family": "Chao", "given": "Hsiao-Tuan", "initials": "HT", "orcid": "0000-0002-2854-5470", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8246a8e3e77a494082f022ec5e831bda.json"}}, {"family": "Rosenfeld", "given": "Jill A", "initials": "JA"}, {"family": "Liu", "given": "Pengfei", "initials": "P", "orcid": "0000-0002-4177-709X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c52ef5bf8b1349de8e81166965711eb7.json"}}, {"family": "Ek", "given": "Marlene", "initials": "M"}, {"family": "Schuy", "given": "Jakob", "initials": "J"}, {"family": "Ameur", "given": "Adam", "initials": "A", "orcid": "0000-0001-6085-6749", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a8b8ce05cf7f49aeb3199b5938b9f160.json"}}, {"family": "Dai", "given": "Hongzheng", "initials": "H"}, {"family": "Undiagnosed Diseases Network", "given": "", "initials": ""}, {"family": "Hwang", "given": "James Paul", "initials": "JP"}, {"family": "Sedlazeck", "given": "Fritz J", "initials": "FJ"}, {"family": "Bi", "given": "Weimin", "initials": "W"}, {"family": "Marom", "given": "Ronit", "initials": "R"}, {"family": "Wincent", "given": "Josephine", "initials": "J"}, {"family": "Nordgren", "given": "Ann", "initials": "A", "orcid": "0000-0003-3285-4281", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/02de5158a75e4fa9a5c7b8bf417a8fea.json"}}, {"family": "Carvalho", "given": "Claudia M B", "initials": "CMB"}, {"family": "Lindstrand", "given": "Anna", "initials": "A", "orcid": "0000-0003-0806-5602", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3d28fb4cc61f4033b2ac525fed3d6b94.json"}}], "type": "journal article", "published": "2024-11-20", "journal": {"title": "Genome Res", "issn": "1549-5469", "volume": "34", "issue": "11", "pages": "1785-1797", "issn-l": "1088-9051"}, "abstract": "Chromosomal inversions (INVs) are particularly challenging to detect due to their copy-number neutral state and association with repetitive regions. Inversions represent about 1/20 of all balanced structural chromosome aberrations and can lead to disease by gene disruption or altering regulatory regions of dosage-sensitive genes in cis Short-read genome sequencing (srGS) can only resolve \u223c70% of cytogenetically visible inversions referred to clinical diagnostic laboratories, likely due to breakpoints in repetitive regions. Here, we study 12 inversions by long-read genome sequencing (lrGS) (n = 9) or srGS (n = 3) and resolve nine of them. In four cases, the inversion breakpoint region was missing from at least one of the human reference genomes (GRCh37, GRCh38, T2T-CHM13) and a reference agnostic analysis was needed. One of these cases, an INV9 mappable only in de novo assembled lrGS data using T2T-CHM13 disrupts EHMT1 consistent with a Mendelian diagnosis (Kleefstra syndrome 1; MIM#610253). Next, by pairwise comparison between T2T-CHM13, GRCh37, and GRCh38, as well as the chimpanzee and bonobo, we show that hundreds of megabases of sequence are missing from at least one human reference, highlighting that primate genomes contribute to genomic diversity. Aligning population genomic data to these regions indicated that these regions are variable between individuals. Our analysis emphasizes that T2T-CHM13 is necessary to maximize the value of lrGS for optimal inversion detection in clinical diagnostics. These results highlight the importance of leveraging diverse and comprehensive reference genomes to resolve unsolved molecular cases in rare diseases.", "doi": "10.1101/gr.279346.124", "pmid": "39486878", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC11610578"}, {"db": "pii", "key": "gr.279346.124"}, {"db": "medline", "key": "9509184"}], "notes": [], "created": "2026-09-23T13:48:47.210Z", "modified": "2026-09-23T13:48:47.384Z"}, {"entity": "publication", "iuid": "cb4e4e8aaf014ad2aa895854196248b3", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/cb4e4e8aaf014ad2aa895854196248b3.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/cb4e4e8aaf014ad2aa895854196248b3"}}, "title": "Novel pathogenic genomic variants leading to autosomal dominant and recessive Robinow syndrome.", "authors": [{"family": "Zhang", "given": "Chaofan", "initials": "C", "orcid": "0000-0003-0504-5999", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/541531103b3e4ffc802be0073482cb6a.json"}}, {"family": "Mazzeu", "given": "Juliana F", "initials": "JF", "orcid": "0000-0002-6161-0510", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d988b145c3e147588b67b85fb994e0bb.json"}}, {"family": "Eisfeldt", "given": "Jesper", "initials": "J"}, {"family": "Grochowski", "given": "Christopher M", "initials": "CM", "orcid": "0000-0002-3884-7720", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/88a70acbf92744869c3e9c067f5278a6.json"}}, {"family": "White", "given": "Janson", "initials": "J"}, {"family": "Akdemir", "given": "Zeynep C", "initials": "ZC"}, {"family": "Jhangiani", "given": "Shalini N", "initials": "SN"}, {"family": "Muzny", "given": "Donna M", "initials": "DM"}, {"family": "Gibbs", "given": "Richard A", "initials": "RA", "orcid": "0000-0002-1356-5698", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/cc9f89d4859042c49cca44bbcd01c92e.json"}}, {"family": "Lindstrand", "given": "Anna", "initials": "A"}, {"family": "Lupski", "given": "James R", "initials": "JR", "orcid": "0000-0001-9907-9246", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d7abcaff111c4272ac9347d97a4b520d.json"}}, {"family": "Sutton", "given": "V Reid", "initials": "VR"}, {"family": "Carvalho", "given": "Claudia M B", "initials": "CMB", "orcid": "0000-0002-2090-298X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/957f6ddd88b24cf3aee597cf2095ec56.json"}}], "type": "journal article", "published": "2021-12-00", "journal": {"title": "Am. J. Med. Genet. A", "issn": "1552-4833", "volume": "185", "issue": "12", "pages": "3593-3600", "issn-l": "1552-4825"}, "abstract": "Robinow syndrome (RS) is a genetically heterogeneous disorder characterized by skeletal dysplasia and a distinctive facial appearance. Previous studies have revealed locus heterogeneity with rare variants in DVL1, DVL3, FZD2, NXN, ROR2, and WNT5A underlying the etiology of RS. The aforementioned \"Robinow-associated genes\" and their gene products all play a role in the WNT/planar cell polarity signaling pathway. We performed gene-targeted Sanger sequencing, exome sequencing, genome sequencing, and array comparative genomic hybridization on four subjects with a clinical diagnosis of RS who had not had prior DNA testing. Individuals in our cohort were found to carry pathogenic or likely pathogenic variants in three RS related genes: DVL1, ROR2, and NXN. One subject was found to have a nonsense variant (c.817C > T [p.Gln273*]) in NXN in trans with an ~1 Mb telomeric deletion on chromosome 17p containing NXN, which supports our contention that biallelic NXN variant alleles are responsible for a novel autosomal recessive RS locus. These findings provide increased understanding of the role of WNT signaling in skeletal development and maintenance. These data further support the hypothesis that dysregulation of the noncanonical WNT pathway in humans gives rise to RS.", "doi": "10.1002/ajmg.a.61908", "pmid": "33048444", "labels": [], "xrefs": [{"db": "mid", "key": "NIHMS1735294"}, {"db": "pmc", "key": "PMC8445516"}], "notes": [], "created": "2026-09-23T08:49:15.112Z", "modified": "2026-09-23T08:49:15.407Z"}, {"entity": "publication", "iuid": "5ac05fc995b94fcb937c49c3025a5dd1", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/5ac05fc995b94fcb937c49c3025a5dd1.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/5ac05fc995b94fcb937c49c3025a5dd1"}}, "title": "Cytogenetically visible inversions are formed by multiple molecular mechanisms.", "authors": [{"family": "Pettersson", "given": "Maria", "initials": "M", "orcid": "0000-0003-3120-1625", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/12ccdc228a31454b8d43136e9708350b.json"}}, {"family": "Grochowski", "given": "Christopher M", "initials": "CM", "orcid": "0000-0002-3884-7720", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/88a70acbf92744869c3e9c067f5278a6.json"}}, {"family": "Wincent", "given": "Josephine", "initials": "J"}, {"family": "Eisfeldt", "given": "Jesper", "initials": "J", "orcid": "0000-0003-3716-4917", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/83d05cbf798f4b48800dc89b57427cf2.json"}}, {"family": "Breman", "given": "Amy M", "initials": "AM"}, {"family": "Cheung", "given": "Sau W", "initials": "SW"}, {"family": "Krepischi", "given": "Ana C V", "initials": "ACV"}, {"family": "Rosenberg", "given": "Carla", "initials": "C"}, {"family": "Lupski", "given": "James R", "initials": "JR", "orcid": "0000-0001-9907-9246", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d7abcaff111c4272ac9347d97a4b520d.json"}}, {"family": "Ottosson", "given": "Jesper", "initials": "J"}, {"family": "Lovmar", "given": "Lovisa", "initials": "L"}, {"family": "Gacic", "given": "Jelena", "initials": "J"}, {"family": "Lundberg", "given": "Elisabeth S", "initials": "ES"}, {"family": "Nilsson", "given": "Daniel", "initials": "D"}, {"family": "Carvalho", "given": "Claudia M B", "initials": "CMB", "orcid": "0000-0002-2090-298X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/957f6ddd88b24cf3aee597cf2095ec56.json"}}, {"family": "Lindstrand", "given": "Anna", "initials": "A", "orcid": "0000-0003-0806-5602", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3d28fb4cc61f4033b2ac525fed3d6b94.json"}}], "type": "journal article", "published": "2020-11-00", "journal": {"title": "Hum. Mutat.", "issn": "1098-1004", "volume": "41", "issue": "11", "pages": "1979-1998", "issn-l": "1059-7794"}, "abstract": "Cytogenetically detected inversions are generally assumed to be copy number and phenotypically neutral events. While nonallelic homologous recombination is thought to play a major role, recent data suggest the involvement of other molecular mechanisms in inversion formation. Using a combination of short-read whole-genome sequencing (WGS), 10X Genomics Chromium WGS, droplet digital polymerase chain reaction and array comparative genomic hybridization we investigated the genomic structure of 18 large unique cytogenetically detected chromosomal inversions and achieved nucleotide resolution of at least one chromosomal inversion junction for 13/18 (72%). Surprisingly, we observed that seemingly copy number neutral inversions can be accompanied by a copy-number gain of up to 350 kb and local genomic complexities (3/18, 17%). In the resolved inversions, the mutational signatures are consistent with nonhomologous end-joining (8/13, 62%) or microhomology-mediated break-induced replication (5/13, 38%). Our study indicates that short-read 30x coverage WGS can detect a substantial fraction of chromosomal inversions. Moreover, replication-based mechanisms are responsible for approximately 38% of those events leading to a significant proportion of inversions that are actually accompanied by additional copy-number variation potentially contributing to the overall phenotypic presentation of those patients.", "doi": "10.1002/humu.24106", "pmid": "32906200", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC7702065"}], "notes": [], "created": "2026-09-23T10:09:21.042Z", "modified": "2026-09-23T10:47:38.791Z"}]}