Browsing by Subject "Segmental duplication"

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    A 360-kb interchromosomal duplication of the human HYDIN locus
    (Elsevier, 2006) Doggett, Norman A.; Xie, Gary; Meincke, Linda J.; Sutherland, Robert D.; Mundt, Mark O.; Berbari, Nicolas F.; Davy, Brian E.; Robinson, Michael L.; Rudd, M. Katharine; Weber, James L.; Stallings, Raymond L.; Han, Cliff; Biology, School of Science
    The HYDIN gene located in human chromosome band 16q22.2 is a large gene encompassing 423 kb of genomic DNA that has been suggested as a candidate for an autosomal recessive form of congenital hydrocephalus. We have found that the human HYDIN locus has been very recently duplicated, with a nearly identical 360-kb paralogous segment inserted on chromosome 1q21.1. The duplication, among the largest interchromosomal segmental duplications described in humans, is not accounted for in the current human genome assembly and appears to be part of a greater than 550-kb contig that must lie within 1 of the 11 sequence gaps currently remaining in 1q21.1. Both copies of the HYDIN gene are expressed in alternatively spliced transcripts. Elucidation of the role of HYDIN in human disease susceptibility will require careful discrimination among the paralogous copies.
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    An evolutionary driver of interspersed segmental duplications in primates
    (BMC, 2020-08-10) Cantsilieris, Stuart; Sunkin, Susan M.; Johnson, Matthew E.; Anaclerio, Fabio; Huddleston, John; Baker, Carl; Dougherty, Max L.; Underwood, Jason G.; Sulovari, Arvis; Hsieh, PingHsun; Mao, Yafei; Catacchio, Claudia Rita; Malig, Maika; Welch, AnneMarie E.; Sorensen, Melanie; Munson, Katherine M.; Jiang, Weihong; Girirajan, Santhosh; Ventura, Mario; Lamb, Bruce T.; Conlon, Ronald A.; Eichler, Evan E.; Medical and Molecular Genetics, School of Medicine
    Background The complex interspersed pattern of segmental duplications in humans is responsible for rearrangements associated with neurodevelopmental disease, including the emergence of novel genes important in human brain evolution. We investigate the evolution of LCR16a, a putative driver of this phenomenon that encodes one of the most rapidly evolving human–ape gene families, nuclear pore interacting protein (NPIP). Results Comparative analysis shows that LCR16a has independently expanded in five primate lineages over the last 35 million years of primate evolution. The expansions are associated with independent lineage-specific segmental duplications flanking LCR16a leading to the emergence of large interspersed duplication blocks at non-orthologous chromosomal locations in each primate lineage. The intron-exon structure of the NPIP gene family has changed dramatically throughout primate evolution with different branches showing characteristic gene models yet maintaining an open reading frame. In the African ape lineage, we detect signatures of positive selection that occurred after a transition to more ubiquitous expression among great ape tissues when compared to Old World and New World monkeys. Mouse transgenic experiments from baboon and human genomic loci confirm these expression differences and suggest that the broader ape expression pattern arose due to mutational changes that emerged in cis. Conclusions LCR16a promotes serial interspersed duplications and creates hotspots of genomic instability that appear to be an ancient property of primate genomes. Dramatic changes to NPIP gene structure and altered tissue expression preceded major bouts of positive selection in the African ape lineage, suggestive of a gene undergoing strong adaptive evolution.