Recently, large-scale benign copy-number variations (CNVs)--encompassing over 12% of the genome and containing genes considered to be dosage tolerant for human development--were uncovered in the human population. Here we present a family with a novel autosomal-dominantly inherited syndrome characterized by microtia, eye coloboma, and imperforation of the nasolacrimal duct. This phenotype is linked to a cytogenetically visible alteration at 4pter consisting of five copies of a copy-number-variable region, encompassing a low-copy repeat (LCR)-rich sequence. We demonstrate that the approximately 750 kb amplicon occurs in exact tandem copies. This is the first example of an amplified CNV associated with a Mendelian disorder, a discovery that implies that genome screens for genetic disorders should include the analysis of so-called benign CNVs and LCRs.
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http://dx.doi.org/10.1016/j.ajhg.2007.08.001 | DOI Listing |
J Infect Dis
January 2025
Gilead Sciences, Inc., 333 Lakeside Dr., Foster City, CA, 94404 USA.
Background: Lenacapavir is a highly potent first-in-class inhibitor of HIV-1 capsid approved for the treatment of heavily treatment-experienced (HTE) people with HIV-1 (PWH) harboring multidrug resistant (MDR) virus, in combination with an optimized background regimen (OBR). Resistance analyses conducted after 2 years of lenacapavir treatment in the phase 2/3 CAPELLA study are described.
Methods: CAPELLA enrolled viremic HTE PWH with resistance to 2 or more drugs per class in at least 3 of the 4 main drug classes.
Diagn Pathol
January 2025
Department of Pathology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, 100045, China.
Background: A number of genetic aberrations are associated with the BCL6-correpresor gene (BCOR), including internal tandem duplications (ITDs) and gene fusions (BCOR::CCNB3 and BCOR::MAML3), as well as YWHAE::NUTM2, which are found in clear cell sarcoma of the kidney (CCSK), sarcoma with BCOR genetic alterations, primitive myxoid mesenchymal tumor of infancy, and high-grade neuroepithelial tumors in children. Detecting these gene aberrations is crucial for tumor diagnosis. ITDs can be identified by Sanger sequencing or agarose gel electrophoresis.
View Article and Find Full Text PDFBiomolecules
January 2025
Department of Biology, Norwegian University of Science and Technology, 7491 Trondheim, Norway.
Dehydrins (Dhns) are a group of intrinsically disordered land plant proteins that are closely associated with tolerance of dehydrative stress. Dhns are recognized and classified by the presence and sequence of five different conserved segments, varying in length from 8 to 15 residues, separated by highly variable disordered regions. In addition to one or more copies of the diagnostic, fifteen-residue K segment, most Dhns can be classified into one of three major groups based on the mutually exclusive presence of three other conserved segments (H, Y, or F), with all three groups typically incorporating multi-serine S segments.
View Article and Find Full Text PDFJ Biol Chem
January 2025
Department of Biochemistry, Indian Institute of Science, Bangalore 560012, INDIA. Electronic address:
The zinc finger transcription factor Mxr1 (methanol expression regulator 1) of the methylotrophic yeast Komagataella phaffii (formerly Pichia pastoris) harbors a DNA-binding domain (DBD) consisting of two CH zinc fingers (Mxr1ZF) between amino acids 36-101 and a previously identified nine amino acid transactivation domain (9aaTAD) between residues 365-373 (TAD A, QELESSLNA). Beyond this, 21 putative 9aaTADs (designated TAD B-V) located between amino acids 401-1155 remain to be characterized. Here, we demonstrate that a compact synthetic transcription factor composed of Mxr1ZF and three tandem copies of TAD A can activate the transcription of Mxr1 target genes for ethanol and methanol metabolism with specificity and efficiency comparable to the full-length protein.
View Article and Find Full Text PDFmedRxiv
November 2024
Laboratory of Translational Genomics, DCEG, National Cancer Institute, Rockville, MD, USA.
The chromosome 5p15.33 region, which encodes telomerase reverse transcriptase (TERT), harbors multiple germline variants identified by genome-wide association studies (GWAS) as risk for some cancers but protective for others. We characterized a variable number tandem repeat within intron 6 (VNTR6-1, 38-bp repeat unit) and observed a strong association between VNTR6-1 alleles (Short: 24-27 repeats, Long: 40.
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